February 1, 2016
Nicholas Stephanopoulos earns prestigious Air Force Young Investigator award
Arizona State University's innovation winning streak among its next generation of talented faculty has continued. Three ASU researchers — more than any other university in the nation — have been awarded part of $20.6 million in total grants funded through the U.S. Air Force's Young Investigator Research Program (YIP). https://asunow.asu.edu/20160125-asu-top-recipient-prestigious-air-force-young-investigator-awards
As a member of the School of Molecular Sciences and the Center for Molecular Design and Biomimetics in the Biodesign Institute, Nicholas Stephanopoulos will use the three-year YIP award to develop self-assembling protein-DNA hybrid molecules as building blocks for complex materials and nano-devices with applications in medicine, biology, and energy. His work seeks to mimic the complexity of biology and is highly interdisciplinary in nature, combining organic chemistry on protein surfaces, self-assembling peptides, DNA nanotechnology and biomaterials engineering.
ASU Biodesign Institute's Center for Molecular Design and Biomimetics is directed by Hao Yan, a past Air Force YIP recipient and recognized leader in bio-nanotechnology. Yan uses DNA and other basic building blocks to build novel nanotechnology structures at a scale 1,000 times smaller than the width of a human hair.
"Our faculty's innovative approaches to grand challenges have placed them among the top tier of researchers nationally," said Sethuraman "Panch" Panchanathan, senior vice president for Knowledge Enterprise Development at ASU. "The technologies and techniques they create could spark entirely new solutions in biomedicine and energy."
"Stephanopoulos has extended a fine School tradition of winning such awards – several SMS members currently hold NSF CAREER awards, e.g. one DOE, two from NSF, and now this is the first new YIP. It is one of the AFOSR's premier funding competitions, and one that is directed toward young faculty members just starting their professional careers," stated Daniel Buttry, director of the School of Molecular Sciences in the College of Liberal Arts and Sciences.
Career awards provide a good example of the economic benefit that a research university can bring to its state. Each year, Arizona universities pour nearly $1 billion into the Arizona economy from their research activities, most of which are funded by the U.S. government and entities from outside the state. Research money brought in by universities is restricted money that can be used only for the research activity it supports.
The Air Force's YIP program is open to scientists and engineers at research institutions across the United States who received PhD or equivalent degrees in the past five years and who show exceptional ability and promise for conducting basic research.
The YIP program fosters creative basic research in science and engineering, enhance early career development of outstanding young investigators, and increase opportunities for the young investigators to recognize the Air Force mission and the related challenges in science and engineering.
The School of Molecular Sciences in ASU's College of Liberal Arts and Sciences ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry), and in the top eight nationally for research publications in the journals Science and Nature. The School's strong record in interdisciplinary research is also evidenced by its 30th national ranking by the National Science Foundation in total and federally financed higher education research and development expenditures in chemistry.
December 18, 2015
Mechanism of action of the first membrane-integral kinase determined using XFEL
|Graphic shows the structure of diacylglycerol kinase(DgkA) determined with the Free Electron Laser (FEL) in Stanford, Ca. This new structure has been deposited in the protein data bank under the code 4UYO.
The mechanism of the action of an important membrane-integral kinase enzyme has been determined in a collaborative research project between scientists at Trinity College Dublin and ASU. Diacylgylcerol is a small enzyme that plays a role in in bacterial wall synthesis by catalyzing conversion of diacylglycerol to phosphatidic acid. The mechanism of its action has been considered mysterious because its lipid substrates are hydrophobic and its co-substrate is the water soluble ATP. A detailed crystal structure of a ternary complex of the enzyme, a bound lipid and an ATP analogue now supports a mechanism for direct transphosphorylation by this diminutive kinase.
The structures of the complex, the wild type enzyme and several mutants were determined using the X-ray free-electron laser at the Stanford Linear Accelerator Center. According to Petra Fromme, the director of the Center for Applied Structural Discovery at Arizona State University's Biodesign Institute and a co-author of the current study,"this is the first structure of a protein that is a membrane-integral enzyme and important biocatalyst in the cell."
Diacylglycerol kinase is of interest because it is the smallest known kinase and is one of the research targets for the NIH funded Center for Membrane Proteins in Infectious Diseases at ASU, which is devoted to unraveling the molecular basis of viral and bacterial proteins involved in diseases as well as the human proteins defending the body from pathogen attack.
The article describing the work has just been published in the leading journal Nature Communications.
The team of researchers at ASU includes the faculty Wei Liu, Petra Fromme and Raimund Fromme from the School of Molecular Sciences, and John Spence, Uwe Weierstall and Nadia Zatsepin from the Department of Physics, the researcher Ingo Grotjohann as well as the graduate students Shibom Basu, Christopher Kupitz and Kimberley Rendek.
November 25, 2015
Petra Fromme receives highest faculty honor
Petra Fromme, the Paul V Galvin Professor of chemistry and biochemistry in the School of Molecular Sciences, has been named Regent's Professor. Regents' Professor is the highest faculty honor and goes to full professors from one of the three Arizona public universities whose exceptional achievements have brought them national or international distinction. Fromme was nominated by ASU President Michael Crow and approved by the Arizona Board of Regents.
Fromme, who has pioneered the study of membrane proteins, came to ASU in 2002 from the Technical University of Berlin, and was drawn by the university's commitment to innovation. She said that her German colleagues were surprised when she chose ASU over two offers to become department chair of biophysics in Germany. "I turned them down to come to ASU and they could not understand it, why I would want to go to the middle of the desert," she said." I was attracted to ASU because of the unique, innovative and interdisciplinary research environment, which let my research further thrive beyond what would have ever been possible at any other university in Germany or the US."
Fromme is a world expert on proteins and has been a pioneer in using new technology to determine their molecular structures. Her discoveries and innovative research methods, which incorporate aspects of both physics and engineering, will potentially lead to new drugs to fight deadly diseases and new methods of creating clean energy.
Fromme directs the Center for Membrane Proteins in Infectious Diseases at ASU and was part of an international team of researchers who demonstrated the first use of X-ray Free Electron Lasers to determine the three-dimensional structure of a protein. In 2012, the journal Science cited the team's research as one of the top 10 breakthroughs of the year.
Fromme also is director of the new Center for Applied Structural Discovery at the Biodesign Institute, where 12 faculty and students from different disciplines work together on innovative projects to understand the structure and dynamics of proteins, potentially leading to improved manmade technologies.
Fromme has over two hundred publications in major scientific journals. Last year she was the leader of an international team and senior author of a paper in the prestigious journal Nature that showed how X-ray laser technology can be used to obtain an atom level description of the very first moments photosynthesis in action, as it splits water into protons, electrons and oxygen. "This study is the first step towards our ultimate goal of unraveling the secrets of water splitting and obtaining molecular movies of biomolecules," said Fromme.
"Each time we work on novel ideas that have never been formulated before, other scientists say it's impossible until we show it's possible," said Fromme.
In receiving this honor, Fromme joins Austen Angell, Peter Buseck, Ana Moore, Tom Moore, Stuart Lindsay, Bob Pettit, all Regents' professors in the School of Molecular Sciences. Devens Gust, Carleton Moore and Mike O'Keefe are Emeritus Regents' professors.
Cynthia Burrows to deliver Fall Eyring Lecture Series
Cynthia J. Burrows is the Thatcher Distinguished Professor of Chemistry at the University of Utah and presently Chair of the Department of Chemistry. She was raised in St. Paul, Minnesota and Boulder, Colorado. Her early training was in physical organic chemistry with professor Stan Cristol at the University of Colorado (B. A. 1975) and profesor Barry Carpenter at Cornell University (Ph.D., 1982), followed by a NSF-CNRS postdoctoral fellowship in the laboratory of Prof. Jean-Marie Lehn, Universite Louis Pasteur, Strasbourg (1981-83). From 1983-1995, she was on the faculty at the Stony Brook University, before returning to the West to take a position at the University of Utah in Salt Lake City in 1995.
The Burrows research group investigates the chemistry and biochemistry of modified bases in DNA and RNA with a focus on oxidative stress, an underlying component of age-related diseases such as cancer. The approach is multi-disciplinary involving the organic chemistry of base modification in DNA, the enzymology of polymerase bypass and DNA repair, biophysical studies of the effects of base modification, single-molecule studies of DNA and RNA in nanopores, and cellular studies of synthetically modified oligomers.
Professor Burrows served as Senior Editor of the Journal of Organic Chemistry for many years and since January 2014 is Editor-in-Chief of Accounts of Chemical Research. She is a past recipient of the Robert Parry Teaching Award and the University Distinguished Teaching Award; her research was recognized with the ACS Utah Award, ACS Cope Scholar Award, and the University of Utah's Distinguished Creative and Scholarly Research Award. She was inducted into the American Academy of Arts and Sciences in 2009 and elected to the National Academy of Sciences in 2014. In 2013 she was appointed the inaugural holder of the Thatcher Presidential Endowed Chair of Biological Chemistry at the University of Utah.
Eyring General Lecture -"Peering into the Dark Matter of DNA: Structures and Functions beyond Watson & Crick"
Eyring Technical Lecture - "Single-Molecule Analysis of the Effects of Oxidative Stress on G:C-rich Sequences in DNA"
September 10, 2015
ASU team develops quick way to determine bacteria's antibiotic resistance
Bacteria's ability to become resistant to antibiotics is a growing issue in health care: Resistant strains result in prolonged illnesses and higher mortality rates.
One way to combat this is to determine bacteria's antibiotic resistance in a given patient, but that often takes days - and time is crucial in treatment. ASU scientists have developed a technique that can sort antibiotic-resistant from "susceptible" bacteria, and it happens in a matter of minutes.
The microfluidic technology, developed in the lab of professor Mark Hayes in the School of Molecular Sciences at Arizona State University, uses microscale electric field gradients, acting on extremely small samples, to tell the difference between the two strains (antibiotic-resistant and antibiotic-susceptible) of Staphylococcus epidermidis.
It's part of a changing approach to bacteria.
It's part of a changing approach to bacteria.
After a multi-decade "sledgehammer" approach, focused on killing all bacteria via soaps, detergents, antibiotics and hand sanitizers, scientists are now moving to subtler methods based on a better understanding of the complex bacterial system in our bodies and in the world around us.
The average human has more than 100 trillion microbes in and on his/her body. That's nine times the number of cells that make up the entire human body. Armies of bacteria sneak into our bodies the moment we are born, uninvited but necessary guests. We can't do without them.
Bacteria have, by evolution, the ability to rapidly adopt beneficial genomic alterations. One type of adaptation is resistance to antibiotics, and this is becoming a huge and worldwide problem.
National summary data from the Centers for Disease Control and Prevention indicate that each year in the United States, at least 2 million people acquire serious infections with antibiotic-resistant strains of bacteria. At least 23,000 people die as a direct result of these infections, and many more die from related complications.
It is not just humans that are threatened by this growing adaptation. A study reported in Science just last week finds a wide variety of African wildlife harbor drug-resistant microbes similar to those found in humans living in nearby villages.
Antibiotic-resistance adaptation is a natural phenomenon. When an antibiotic is used, bacteria that can resist that antibiotic obviously have a greater chance of survival than those that are susceptible, and so the resistance passes to the next generation.
Some of the most notorious antibiotic-resistant strains and species belong to the genus Staphylococcus. They are typically classified as pathogenic or non-pathogenic based on production of the enzyme coagulase. Staphylococcus epidermidis does not produce coagulase, and it is generally less invasive than Staphylococcus aureus. In fact, it is a normal and commensal resident of human skin.
In recent decades, however, Staphylococcus epidermidis has increasingly emerged as a cause of multi-resistant hospital-acquired infections. Immunocompromised patients, indwelling medical devices, and surgically implanted prostheses provide suitable environments for Staphylococcus epidermidis to propagate and form biofilms.
This is where the project began, as a collaboration with orthopedic surgeon Dr. Alex McLaren and his team member and bioengineer Dr. Ryan McLemore of Banner Good Samaritan Medical Center, Phoenix, along with Dr. Mark Spangehl of the Mayo Clinic College of Medicine, Arizona.
By most metrics the antibiotic-resistant and susceptible strains of Staphylococcus epidermidis are phenotypically identical, and thus present a major challenge to traditional analytical separation techniques. This is where the ASU technology is finding its place.
Current clinical approaches to determination of antibiotic resistance often require two or more days to obtain results. They typically rely upon treating the bacteria with antibiotics, then observing colony growth patterns. The long turnaround times lead to increased reliance upon broad-spectrum antimicrobials and generally lead to suboptimal outcomes for patients (including increased mortality rates).
Scientists in the Hayes group at ASU's School of Molecular Sciences - soon to become the School of Molecular Sciences - are enabling a handheld, battery-operated device that might deliver answers in minutes, instead of days.
Identification takes place within a microscopically small channel in a chip made from glass and silicone polymer. The microchannel features sawtooth shapes that allow researchers to sort and concentrate microbes based on their unique electrical properties.
The phenomenon that makes this work is called dielectrophoresis, which involves an applied voltage that exerts force upon the bacteria. This force acts like a coin-sorter, causing bacteria to become trapped at different points along the channel. Where they stop, and at what voltage, depends on their molecular and electrical properties.
Using this approach, Hayes' team, including graduate students Paul V. Jones and Shannon (Huey) Hilton, has separated extremely similar bacteria - Gentamicin (antibiotic) resistant and susceptible bacteria. Their results have recently been published in the journal Analyst.
"The important thing for the patient and the doctor is getting the right answer right away. By advancing a fundamental area of science, we are able to create an entirely new way to differentiate these micro-organisms," Hayes said.
"And it turns out that we have a core mechanism that could be integrated with smartphones and be widely, and cheaply, distributed. Frankly, we only hoped that this strategy could work this well, even though our theoretical calculations suggest that it could."
The researchers fluorescently labeled the two strains (each with a different dye) of Staphylococcus epidermidis so that they could be visually distinguished during the separation process. They injected the cells into each channel and simply applied voltage to drive the cells downstream. The geometric features of the channel shape the electric field, creating regions of different intensity. This field creates the dielectrophoretic force that allows some cells to pass, while trapping others based on their phenotype.
This separation has significant potential implications for health care, as rapid and early detection will significantly improve therapeutic outcomes. The current results establish a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship.
This work was supported by NIH, National Institute of Allergy and Infectious Diseases.
The School of Molecular Sciences is an academic unit in ASU's College of Liberal Arts and Sciences.
Jenny Green, email@example.com
School of Molecular Sciences
July 23, 2015
Scientists determine structure of important drug target using groundbreaking approach
Tempe, Arizona (July 23, 2015)-Using the brightest X-ray laser in the world, scientists have determined the structure of a molecular complex that is responsible for our sense of sight.
Researchers at Arizona State University's Biodesign Institute Center for Applied Structural Discovery (CASD) collaborated with an international team of researchers from 19 institutions working to develop a roadmap for more selectively targeting pathways for drug treatment. The innovative approach may lead to more effective therapies with fewer side effects, particularly for diseases such as cancer, heart disease and neurodegenerative disorders.
The study, "Crystal Structure of Rhodopsin Bound to Arrestin Determined by Femtosecond X-ray Laser," was published online in the journal Nature.
The new research focuses on a signaling protein called arrestin, which plays a vital role in cellular communication, and a G protein-coupled receptor (GPCR) called rhodopsin, which is instrumental in our sense of sight.
Arrestin, as well as other signaling proteins known as G proteins, link up with GPCRs to convey important instructions for many essential physiological functions, such as growth and hormone regulation. G protein and arrestin pathways are physiologically distinct; GPCR drugs that selectively modulate one pathway are often preferred as they can have better therapeutic benefits with fewer undesirable side effects than non-selective drugs.
"Arrestin and G proteins are the yin and the yang of regulating GPCR function," said H. Eric Xu, Ph.D., from Van Andel Research Institute (VARI), Grand Rapids, MI who led the study. "In the realm of drug development, a detailed understanding of the structure, interaction and function of each of these groups of proteins is vital to developing effective therapies. The more specific the interaction, the better the drugs tend to work while also lowering the chance of side effects."
Researchers at CASD helped to pioneer a new technique called femtosecond crystallography, which takes advantage of a cutting edge X-ray Free Electron Laser (XFEL) instrument at the Department of Energy's (DOE) SLAC National Accelerator Laboratory, Stanford. The instrument can generate X-ray pulses that are a billion times brighter than previous X-ray sources, and that are so short that the biomolecule structure is imaged before it is destroyed. This capability allowed the team to create the three-dimensional image of the arrestin-rhodopsin complex at an atomic level-a much higher resolution than is possible with conventional X-ray technology. (Femtosecond X-ray pulses are almost unfathomably brief. The time difference between one femtosecond and a second is the same as the difference between a second and 32 million years!)
"This is an important step forward in understanding how human vision works at the molecular level, and a dramatic demonstration of the power of the X-ray laser at the SLAC DOE National Laboratory to reveal new molecular structures and their function," said John Spence, Regents' Professor of physics, Scientific Director for the National Science Foundation's BioXFEL Science and Technology Center and member of the CASD research team.
Contributions from ASU researchers included crystallization and biophysical characterization of the rhodopsin-arrestin constructs and crystals, X-ray data collection and evaluation, as well as development of the devices that deliver the stream of nanocrystals.
The work is based on a team effort of ASU faculty, Wei Liu, Petra Fromme, Raimund Fromme John Spence, and Uwe Weierstall with their teams of researchers and students including: researchers Nadia Zatsepin and Stella Lisova from the Department of Physics as well as the graduate students Shibom Basu, Jesse Coe, Chelsie Conrad and Shatabdi Roy-Chowdhury from the School of Molecular Sciences, and Daniel James and Dingjie Wang from the Department of Physics.
In the future, the researchers hope to study the signaling protein arrestin with other GPCRs that are involved in heart disease and cancer as well as to use this structure to screen for drug compounds that are designed to treat these diseases with far fewer side effects, which will have a dramatic impact on human health.
"There are a number of other GPCRs that are critical to many of the processes in our bodies, like seeing, touching, hearing, smelling, tasting and feeling pain, and when they become dysfunctional it can lead to devastating diseases such as cancer" said Wei Liu, Assistant Professor in the School of Molecular Sciences and member of CASD. "This study provides important clues about how we can improve human health and make important progress in the fight against cancer and other incurable human diseases."
Contact: Richard Harth firstname.lastname@example.org 480-727-0378
July 20 , 2015
Rare form: novel structures built from DNA emerge
DNA, the molecular foundation of life, has new tricks up its sleeve. The four bases from which it is composed snap together like jigsaw pieces and can be artificially manipulated to construct endlessly varied forms in two and three dimensions.
The technique, known as DNA origami, promises to bring futuristic microelectronics and biomedical innovations to market.
Hao Yan, a researcher at Arizona State University's Biodesign Institute, has worked for many years to refine the technique. His aim is to compose new sets of design rules, vastly expanding the range of nanoscale architectures generated by the method. In new research, a variety of innovative nanoforms are described, each displaying unprecedented design control.
Yan is the Milton D. Glick Distinguished Chair of Chemistry and Biochemistry and directs Biodesign's Center for Molecular Design and Biomimetics.
In the current study, complex nano-forms displaying arbitrary wireframe architectures have been created, using a new set of design rules. "Earlier design methods used strategies including parallel arrangement of DNA helices to approximate arbitrary shapes, but precise fine-tuning of DNA wireframe architectures that connect vertices in 3D space has required a new approach," Yan says.
Yan has long been fascinated with Nature's seemingly boundless capacity for design innovation. The new study describes wireframe structures of high complexity and programmability, fabricated through the precise control of branching and curvature, using novel organizational principles for the designs. (Wireframes are skeletal three-dimensional models represented purely through lines and vertices.)
The resulting nanoforms include symmetrical lattice arrays, quasicrystalline structures, curvilinear arrays, and a simple wire art sketch in the 100-nm scale, as well as 3D objects including a snub cube with 60 edges and 24 vertices and a reconfigurable Archimedean solid that can be controlled to make the unfolding and refolding transitions between 3D and 2D.
The research appears in the advanced online edition of the journal Nature Nanotechnology.
In previous investigations, the Yan group created subtle architectural forms at an astonishingly minute scale, some measuring only tens of nanometers across-roughly the diameter of a virus particle. These nano-objects include spheres, spirals, flasks, Möbius forms, and even an autonomous spider-like robot capable of following a prepared DNA track.
The technique of DNA origami capitalizes on the simple base-pairing properties of DNA, a molecule built from the four nucleotides Adenine (A), Thymine (T) Cytosine (C) and (Guanine). The rules of the game are simple: A's always pair with T's and C's with G's. Using this abbreviated vocabulary, the myriad body plans of all living organisms are constructed; though duplicating even Nature's simpler designs has required great ingenuity.
The basic idea of DNA origami is to use a length of single-stranded DNA as a scaffold for the desired shape. Base-pairing of complementary nucleotides causes the form to fold and self-assemble. The process is guided by the addition of shorter "staple strands," which act to help fold the scaffold and to hold the resulting structure together. Various imaging technologies are used to observe the tiny structures, including fluorescence-, electron- and atomic force microscopy.
Although DNA origami originally produced nanoarchitectures of purely aesthetic interest, refinements of the technique have opened the door to a range of exciting applications including molecular cages for the encapsulation of molecules, enzyme immobilization and catalysis, chemical and biological sensing tools, drug delivery mechanisms, and molecular computing devices.
The technique described in the new study takes this approach a step further, allowing researchers to overcome local symmetry restrictions, creating wireframe architectures with higher order arbitrariness and complexity. Here, each line segment and vertex is individually designed and controlled. The number of arms emanating from each vertex may be varied from 2 to 10 and the precise angles between adjacent arms can be modified.
In the current study, the method was first applied to symmetrical, regularly repeating polygonal designs, including hexagonal, square and triangular tiling geometries. Such common designs are known as tessellation patterns. A clever strategy involving a series of bridges and loops was used to properly route the scaffold strand, allowing it to pass through the entire structure, touching all lines of the wireframe once and only once. Staple strands were then applied to complete the designs.
In subsequent stages, the researchers created more complex wireframe structures, without the local translational symmetry found in the tessellation patterns. Three such patterns were made, including a star shape, a 5-fold Penrose tile and an 8-fold quasicrystalline pattern. (Quasicrystals are structures that are highly ordered but non-periodic. Such patterns can continuously fill available space, but are not translationally symmetric.)
Loop structures inserted into staple strands and unpaired nucleotides at the vertex points of the scaffold strands were also used, allowing researchers to perform precision modifications to the angles of junction arms.
The new design rules were next tested with the assembly of increasingly complex nanostructures, involving vertices ranging from 2 to 10 arms, with many different angles and curvatures involved, including a complex pattern of birds and flowers.
The accuracy of the design was subsequently confirmed by AFM imaging, proving that the method could successfully yield highly sophisticated wireframe DNA nanostructures. The method was then adapted to produce a number of 3D structures as well, including a cuboctahedron, and another Archimedian solid known as a snub cube-a structure with 60 edges, 24 vertices and 38 faces, including 6 squares and 32 equilateral triangles.
The authors stress that the new design innovations described can be used to compose and construct any imaginable wireframe nanostructure- a significant advancement for the burgeoning field. On the horizon, nanoscale structures may one day be marshaled to hunt cancer cells in the body or act as robot assembly lines for the design of new drugs.
Fei Zhang1, Shuoxing Jiang1, Siyu Wu2, Yulin Li2, Chengde Mao2, Yan Liu1* and Hao Yan1*
1Center for Molecular Design and Biomimetics, The Biodesign Institute and the School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA
2Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Written by: Richard Harth Science Writer: Biodesign Institute email@example.com
May 27, 2015
Herckes group's research on PBS website and in newshour
Scientists trace cancer-causing chemical in drinking water back to methadone
Like death and taxes, at some point in life, drinking someone else's human waste becomes inevitable.
When water flows from the many pipes of our homes, the first stop is a wastewater treatment factory, where most hazardous chemicals and microbes are removed. In an ideal scenario, city planners have geographically positioned wastewater facilities so that none of the drainage flows into another's city's drinking water supply. But if you live downstream from any population, then you're likely drinking someone's wastewater, says Arizona State University environmental engineer Paul Westerhoff.
Enter methadone. Methadone is the latest member of an infamous club. Like birth control hormones and the antibacterial ingredient triclosan, methadone leaks into waterways and poses a health risk when it filters into our drinking water, according to a new study in the journal Environmental Science & Technology Letters.
But unlike some forms of pharmaceutical pollution, the danger of methadone waste doesn't come from the drug itself, but from a chemical reaction with a common wastewater disinfectant. The product of this reaction is the carcinogen N-nitrosodimethylamine or "NDMA" for short. The World Health Organization describes NDMA as "clearly carcinogenic" due to its ability to cause stomach and colon cancer after ingestion.
"It's a very important paper, as NDMA is a very potent carcinogen," said environmental chemist Susan Richardson of the University of South Carolina, who wasn't involved with the study. "It's being commonly found in drinking water well above the health reference level for cancer, and the U.S. Environmental Protection Agency is currently deciding whether to regulate it."
read more on PBS NEWSLHOUR
"Methadone Contributes to N-Nitrosodimethylamine Formation in Surface Waters and Wastewaters during Chloramination", David Hanigan , E. Michael Thurman, Imma Ferrer, Yang Zhao, Susan Andrews, Jinwei Zhang, Pierre Herckes , and Paul Westerhoff, Environ. Sci. Technol. Lett., Article ASAP, DOI: 10.1021/acs.estlett.5b00096 Publication Date (Web): May 8, 2015.
April 23, 2015
Key blood pressure drug seen in startling new detail
Tempe, AZ- A new Arizona State University research study has revealed the fine details of how an experimental drug works to regulate blood pressure, paving the way to the development of better drugs.
The ASU team's interdisciplinary work -which involved Petra Fromme, Wei Liu, Uwe Weierstall, and researchers and students at Arizona State University's School of Molecular Sciences, Department of Physics, and the Center for Applied Structural Discovery at the Biodesign Institute-may one day help scientists better control blood pressure irregularities with a new class of drugs that could limit harmful side effects.
The new research focuses on a type of drug known as an angiotensin II receptor blocker, or ARB. Used by millions of people each year, ARBs are designed to block a receptor so it cannot bind with angiotensin II, a hormone that constricts blood vessels to cause an increase in blood pressure.
"Uncovering the structure of the angiotensin receptor is a real breakthrough in the development of better drugs to regulate blood pressure," Fromme says. It has been unraveled by a new technique called femtosecond crystallography, pioneered by researchers at ASU and their collaborators.
The technique for uncovering these atomic scale structures uses a jet of tiny crystals that are exposed to super-strong x-ray pulses. These powerful bursts of light destroy any solid material but are so short that the structure of the receptor can be discovered before the molecule is destroyed. The structure reveals-in atomic detail- how the drugs block the receptor.
"Many ARBs have been developed, but the interaction between the drug and the receptor has been unknown at the atomic level," said Vadim Cherezov, a chemistry professor at the University of Southern California, (USC), who led the experiment in collaboration with nine other institutions at SLAC's Linac Coherent Light Source (LCLS) X-ray laser, a DOE Office of Science User Facility.
Solving the structure of the joined ARB and receptor brought researchers a number of surprises. "We have shown that all of the previous molecular models -the best guesses for how receptor and drug fit together -were wrong in many important details," Cherezov said.
Results of the new study-the first to examine the detailed structure of a drug-receptor complex through high-speed x-ray crystallography-are detailed in the April 23 advanced online edition of Cell.
Given the importance of anti-hypertensive drugs, researchers have sought to uncover agents or mechanisms that will more actively and efficiently control blood pressure, streamlining therapy and improving results.
One third of U.S. adults suffer from high blood pressure or hypertension and take prescription medication to treat it. Known as a "silent killer" because the condition often produces no outward symptoms, hypertension is a major risk factor for heart disease and stroke, the leading causes of death in the U.S.
ARBs are a multibillion-dollar industry, with fewer side effects than other hypertension medications. But because their effectiveness at higher doses may be limited, they are often used in combination with other drugs, complicating treatment when patients fail to follow the complete regimen.
In the vast majority of cases, hypertension occurs in primary form, meaning that its underlying causes are unknown. In secondary hypertension, the condition arises as a result of a known affliction including chronic kidney disease, arterial narrowing or a preexisting endocrine disorder.
Left unchecked, severely elevated blood pressure can lead to a "hypertensive crisis," a condition carrying significant risk of complications. These may include visual deterioration due to retinopathy, breathlessness accompanying heart failure, or general malaise due to acute kidney failure. Generally, a hypertensive crisis occurs when some trigger causes already elevated blood pressure to sharply spike.
The new study examined nanoscale crystals of an experimental ARB coupled to an angiotensin II receptor.
The study of such medically important molecules is carried out using brief pulses of intense x-ray light. The tool of choice, a high-speed laser capable of taking vivid snapshots of biological material, uses x-rays a billion times more powerful than conventional light sources.
Like an inkjet printer, a fine spray of tiny crystals of the ARB-receptor pair is injected onto the path of the x-ray beam, which instantly vaporizes the sample.
Crystalized samples are imaged on the scale of femtoseconds. A femtosecond is 0.3 "light micrometers," a timespan so brief that in 1 femtosecond, a light ray would cross a distance barely the size of a virus. The concentrated x-ray beam vaporizes the sample, but the pulse is so short that the delicate structure is captured before the molecule is destroyed.
Using femtosecond x-ray crystallography, the researchers were able to precisely determine the crystal structure of angiotensin II type1 receptor at a remarkable resolution down to 2.9 angstroms (one ten-billionth of a meter-the width of a single hydrogen atom).
Contributions from ASU researchers included the crystallization of samples and biophysical characterization of the drug-receptor constructs, data collection and evaluation, as well as development of the devices that deliver the stream of nanocrystals.
The work is based on a team effort of ASU faculty Petra Fromme, Wei Liu and Uwe Weierstall with their teams of researchers and students that including: Nadia Zatsepin, researcher in the Department of Physics as well as the graduate students Chelsie Conrad and Jesse Coe from the School of Molecular Sciences, and Daniel James, Dingjie Wang, and Garrett Nelson from the Department of Physics.
In the future, the researchers hope to study the receptor in combination with other drug compounds to fill in even more details and accelerate the design of new drugs to modulate blood pressure and improve human health.
"A further exciting avenue would be to construct a molecular movie of the function of the receptor and the changes induced by the drug binding," said Fromme. "By obtaining a movie of the dynamics of the receptor and the drug binding we can eventually design structure-based drugs that block the receptor in action, which might be more efficient and specific, thereby minimizing side effects for the patients."
March 6, 2015
ASU researchers explore longer life cycle for batteries
Lithium-ion batteries are common in consumer electronics. They are one of the most popular types of rechargeable batteries for portable electronics, with a high energy density, no memory effect and only a slow loss of charge when not in use. Beyond consumer electronics, lithium-ion batteries have also grown in popularity for military, electric vehicle and aerospace applications.
Now, researchers at Arizona State University are exploring new energy storage technology that could give the battery an even longer life cycle.
Led by Dan Buttry, professor and chair of ASU's School of Molecular Sciences, the research also involves former undergraduate researcher Jarred Olsen and current graduate student Tylan Watkins. Olsen joined Buttry's group as an undergraduate researcher to work in the ionic liquids area. The work he contributed to this study was performed while he was on an internship at Boulder Ionics working at both Boulder and ASU with Watkins. Olsen is currently a doctoral student at the University of Washington, Seattle.
The research, just published in Nature Communications, brings together scientists from Arizona State University, University of Colorado at Boulder, Sandia National Laboratories, Boulder Ionics Corporation and Seoul National University, Korea.
Jenny Green, firstname.lastname@example.org
Prolonging the life cycle
Room temperature ionic liquids have attracted a great deal of interest in recent years due to their remarkable physicochemical properties, including high thermal stability, wide electrochemical window and low vapor pressure.
"We used a device called a quartz crystal microbalance to measure very tiny mass changes in thin films at the surface of the battery material during charging and discharging," said Buttry. "One of the key features of successful lithium battery materials is that they develop thin films that protect the surface of the battery electrodes, which prolongs the life of the battery. This study documents the development of just such a film in a new type of battery formulation that has many more attractive features than existing commercial lithium batteries."
Buttry added: "The hope is that this new formulation will find its way into commercial use."
The work is part of a larger effort in Buttry's lab that has included funding from the Advanced Research Projects Agency - Energy (ARPA-E) and now from the Army Research Office.
"These were not trivial measurements to make because composite films (meaning a film of the active material in a polymer matrix) are often difficult to use with a quartz crystal microbalance," said Watkins. "Most, if not all, quartz crystal microbalance studies of this sort use very thin films of the active material alone, which means specialty deposition methods must be used. What was cool here is that we were able to make the measurement on a more practical film, something you might realistically see in a commercial battery."
This work provides new science related to the interfacial stability of silicon-based materials while bringing positive exposure to ionic liquid electrochemistry.
By combining a high-performance silicon electrode architecture with a room temperature ionic liquid electrolyte containing the new bis-fluorosulfonylamide anion, the researchers demonstrate a highly energy-dense lithium-ion cell with an impressively long cycling life, maintaining over 75 percent capacity over 500 charge/discharge cycles with almost perfect current efficiency (no wasted electrons).
"This study brings home the fact that energy storage technology still has a lot of room to run, with new technological changes coming at a fast pace," says Buttry. "This is important when considering areas where storage is important, such as grid storage and electric vehicles."
According to Watkins, there are a multitude of reasons why modern society demands more energy dense batteries.
"For some time, silicon anodes have been proposed as replacements for the carbon based anodes found in current state-of-the-art devices as they could potentially give energy densities almost 10 times that of modern anodes," Watkins said. "This exciting collaboration could bring us one step closer to realizing more energy dense batteries with silicon anodes."
School of Molecular Sciences
February 17, 2015
Ariel Anbar named 2015 "Geochemistry Fellow"
Ariel Anbar, President's Professor in the School of Molecular Sciences and the School of Earth & Space Exploration (SESE) and has been elected a Geochemistry Fellow by The Geochemical Society (GS) and The European Association of Geochemistry (EAG).
In 1996, The Geochemical Society and The European Association for Geochemistry established the honorary title of Geochemistry Fellow, to be bestowed upon outstanding scientists who have, over some years, made a major contribution to the field of geochemistry.
The 2015 Geochemical Fellows will receive their honor at the 2015 Goldschmidt Conference in Prague, Czech Republic, this summer.
Anbar joins professor Everett Shock in this honor.
February 16, 2015
ASU Secondary Ion Mass Spectrometry Facility receives million-dollar grant from the National Science Foundation
ASU SIMS facility shrinks geochemical analysis into the nanometer regime
TEMPE, Ariz. - Two secondary ion mass spectrometry (SIMS) laboratories in the Bateman Physical Science Complex were recognized as hotbeds of scientific research, thanks to the expertise of researchers in Arizona State University's School of Earth and Space Exploration (SESE) and the School of Molecular Sciences (DCB). Professors Richard Hervig, Lynda Williams, and Christy Till of SESE and Professor Peter Williams and postdoctoral researcher Maitrayee Bose of DCB have been awarded $1 million over the next three years to operate their joint laboratories as a national facility for research into the Earth Sciences using this high-sensitivity microbeam analysis technique.
SIMS is an analytical tool permitting measurements of elemental concentration and isotope ratios on extremely tiny areas, so that chemical and isotopic variability on scales from a few micrometers down to several nanometers can be determined.
Rick Hervig, email@example.com
Currently, ASU has one of the most extensive arrays of SIMS instrumentation and SIMS expertise in the world. The ASU researchers have been consistently on the leading edge of innovation in micro-elemental analysis. SIMS research at ASU dates back to 1984 with the acquisition of a Cameca (Paris) ims3f ion microscope by Peter Williams, capable of analysis in few-micrometer areas. A more modern and more powerful ims6f microscope was added in 1999 under the leadership of Hervig. Continuing the tradition of being at the leading edge of the instrumentation, Peter Williams (with Hervig, Lynda Williams and other ASU researchers) spearheaded the acquisition of a Cameca NanoSIMS instrument in 2011, with the capability to analyze areas as small as tens of nanometers.
This combination of instruments enables applications to a broad range of scientific problems, including analyses of a wide variety of natural and synthetic inorganic materials from this planet and others, semiconductors and even biological materials.
"We have been operating as an NSF-funded national facility since early 2007," says Hervig, professor in ASU's School of Earth and Space Exploration and director of the ASU SIMS facility. "The 2015 renewal allows us to continue to operate as a facility, and makes the NanoSIMS instrument as well as the existing 6f SIMS lab accessible to students, researchers and faculty."
On the national stage, this facility is a key player in the mix of instrumentation that is required to conduct state-of-the-art microanalytical geochemistry and petrology.
The SESE researchers are widely known for applying their technique to analyze tiny grains in meteorites thought to pre-date our solar system, small fragments of explosive eruptions, clays and nanopores in oil-shale, and characterization of slow elemental and isotopic diffusion in a variety of earth materials, including volcanic minerals.
"With the ability to analyze elemental concentrations in zoned crystals on the nanometer scale using NanoSIMS, we are now able to reconstruct the life history of a magma up to just a few hours before a volcanic eruption and determine the triggers for explosive volcanic eruptions at volcanoes including Yellowstone," says Till, an assistant professor in the School of Earth and Space Exploration.
Hervig has developed many SIMS techniques for geochemistry and applied them to natural samples from this and other planets as well as a variety of synthetic materials. Lynda Williams has used this technique on a range of materials at the organic/inorganic interface, specifically on the role of nanopores in understanding more about the properties of oil shales (and the environmental impact of mining them).
ASU also has built a reputation for developing novel analytical applications and instrumentation and for fundamental research aimed at understanding the ion formation process. While a central focus of the SESE researchers is on earth science problems, the lab is open to others, and the team commonly works with materials scientists and electrical engineers on campus and in the ASU Research Park, in addition to microbiologists and chemists.
Geochemists from around the world travel to the NSF-funded National SIMS Facility on ASU's Tempe campus to use the instruments. Since 2007, from 2 to 12 people (undergraduate and graduate students, post-doctoral researchers, senior research scientists, and faculty) have visited the ASU facility each month. They are usually from the US, but also include visitors from other countries.
One of the anonymous proposal reviewers stated: "We all know that the devil is in the details, and it seems that the scale at which the demons operate gets smaller and smaller with each new advancement in analytical capability. Being able to analyze samples with both the normal and NanoSIMS at the ASU facility will open up new frontiers in our understanding of geological problems, and especially in the ability to examine the timescales of geologic processes." Another reviewer lauded the facility as "one of the most creative and original SIMS labs in the nation."
Speaking on behalf of the co-investigators, Hervig said, "We are flattered to be recognized for our scientific leadership and excited at the prospects for unprecedented nanometer-scale geochemical analyses now possible with the incorporation of the new NanoSIMS instrument into the facility. This is high praise for the senior members of the team, but we are particularly pleased that the NSF reviewers agreed with our emphasis on involving younger researchers - Till and Bose - who are pushing the limits of NanoSIMS analysis in the earth and space sciences."
Nikki Cassis, firstname.lastname@example.org
February 7, 2015
Protein Interactions Enhance Activity of an Oxygen-tolerant, H2 Producing Catalyst
A pressing challenge facing society is the development of sustainable energy sources. In this context, hydrogen has emerged as a possible clean alternative to carbon-based fuels, if scalable and environmentally friendly methods for its production and utilization can be developed. Towards this goal, Dayn Sommer and Dr. Michael Vaughn led by Professor Giovanna Ghirlanda recently designed a new biohybrid catalyst for the production of H2 by functionalizing myoglobin, a natural protein, with cobalt porphyrin. This work was recently featured on the inside cover of Chemical Communications . The hybrid catalyst, CoMyo, is able to efficiently function under aerobic conditions, a property uncommon to H2 production systems. Incorporation into myoglobin enhances the activity of the cobalt porphyrin 4 fold by providing critical secondary-shell interactions to the catalyst. Furthermore, point mutants in the active site modulated the designed system’s activity up to 2 fold more. This work opens doors for chemi-genetic approaches to catalyst design, while demonstrating the important role protein scaffolds play for catalysis in nature.
Reference: Chem Commun (Camb). 2014 Dec 28;50(100):15852-5. doi: 10.1039/c4cc06700b.
A Designed Peptide Mimics Natural Electron Transfer
Many complex enzymes, such as those involved in the life-maintaining processes of photosynthesis and respiration, rely on chains of [4Fe-4S] clusters to shuttle electrons to/from their active sites. Synthetic peptides have been developed that house single [4Fe-4S] clusters, but chemists have struggled to generate a platform that can accommodate two or more clusters, in which the clusters are spaced at an optimal distance for electron transfer. Recent work from Ghirlanda and co-workers, featured in December JACS spotlights, have solved this problem: they have made a protein, DSD-Fdm, that incorporates two [4Fe-4S] clusters spaced 12 Å apart, a distance optimal for electron transfer. This highly stable peptide is able to successfully transfer electrons to cytochrome c, an important natural electron-transfer protein. The team also shows that DSD-Fdm accepts energy from a porphyrin photosensitizer, suggesting that it could be used in designed solar fuel cells. Further, these proteins could be utilized to generate artificial redox pathways for synthetic biology applications.
References: Sommer, D. J., Vaughn, M. D., and Ghirlanda, G. (2014) Protein secondary-shell interactions enhance the photoinduced hydrogen production of cobalt protoporphyrin IX, Chem. Commun. 50, 15852-15855.
Roy, A., Sommer, D. J., Schmitz, R. A., Brown, C. L., Gust, D., Astashkin, A., and Ghirlanda, G. (2014) A De Novo Designed 2[4Fe-4S] Ferredoxin Mimic Mediates Electron Transfer, J. Am. Chem. Soc. 136, 17343-17349
February 4, 2015
Chen lab discovers a new processing pathway for non-coding RNA
All life on earth follows the central dogma of biology: DNA to RNA to protein. DNA stores the genetic information and is transcribed into RNA that carries the information to the machinery used to create proteins. RNA is translated to the various amino acid sequences that fold into a variety of proteins and enzymes in the cell.
This protein-coding RNA, known as messenger RNA (mRNA), goes through a multi-step process to generate a mature functional mRNA. These mRNA molecules receive a protective structure made up of repeated adenosines called a poly(A) tail to protect the RNA from being degraded and also signal that the RNA encodes for a protein. mRNAs also goes through a process known as splicing where unnecessary RNA sequences, known as introns, are removed. After removal of the internal intron, the two neighboring mRNA fragments are joined together to form a single continuous mRNA ready for protein synthesis. This contrasts with another subset of RNA, called non-coding RNA that is not used to create proteins.
Non-coding RNAs play many important roles in the cell and have been implicated in human disease. Some non-coding RNAs are functional and act directly on other molecules in the cell, while others regulate gene expression or act as transport molecules. Telomerase contains an essential non-coding RNA subunit and is a potential target for anti-aging and cancer therapies.
Recently the Chen group discovered a novel mechanism that processes the telomerase RNA precursor into its mature form. This mechanism is highly conserved in filamentous fungi and distinct from the mechanism employed in vertebrates and other eukaryotes. The fungal telomerase RNA precursor initially contains an intron and a poly(A) tail. By hijacking the machinery used to remove mRNA introns and blocking the joining of the two RNA fragments by simply changing the first residue of the intron from G to A, fungal telomerase RNA is cleaved to make the mature RNA. This unique half-splicing reaction thus generates two fragments of RNA, the mature telomerase RNA, used by the telomerase enzyme, and a second fragment that is degraded. As Chen says, "It's amazing how nature continues to surprise us by grabbing bits and pieces from other systems to make a new method for RNA processing." Splicing has been studied for decades and this is the first time that this type of reaction has been found in nature and requires only a single-residue alteration in the 5' splice site of the intron.
Non-coding RNA is emerging as an important player in cellular systems and by finding a novel RNA processing pathway, we may be able to identify new classes of RNA that utilize a similar method for RNA maturation.
The work was been published this month in Nature Communications (Qi, X., D.R. Rand, J.D. Podlevsky, Y. Li, A. Mosig, P.F. Stadler and J.J.-L. Chen, Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA. Nature Communications 6:6105, doi:10.1038/ncomms7105).
"Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal telomerase RNA", Xiaodong Qi, Dustin P. Rand, Joshua D. Podlevsky, Yang Li, Axel Mosig, Peter F. Stadler & Julian J. -L. Chen, Nature Communications 6, Article number: 6105, doi:10.1038/ncomms7105, Published 19 January 2015
Jenny Green, email@example.com
School of Molecular Sciences
Juanary 23, 2015
Tobin Marks to give Spring 2015 Eyring Lectures
Tobin Jay Marks, the Vladimir N. Ipatieff Professor of Chemistry and Professor of Material Science and Engineering at Northwestern University will give the Spring Eyring lectures on February 12 and 13 of this year. https://chemistry.asu.edu/seminar/eyring.asp
Marks received a B.Sc. in Chemistry from the University of Maryland (1966) and Ph.D. from MIT (1971) in Inorganic Chemistry. A master of the molecule in many ways, Marks studies and designs single molecules in order to make better catalysts for new kinds of plastics, while in his molecular optoelectronics work Marks designs arrays of "smart" molecules that will self-assemble into, or spontaneously form, structures that can conduct electricity, switch light on and off or emit and detect light.
"What fascinates me in science is making new things that no one has ever made before and understanding their properties on a fundamental level - and also with a mind toward whether the discoveries might have some useful application for society," says Marks.
During his career, Marks has been honored with some of the most prestigious national and international awards in the fields of inorganic, catalytic, materials and organometallic chemistry. Recent honors include the Wilkinson Medal from Royal Society of Chemistry UK, and the Alan G. MacDiarmid Medal from University of Pennsylvania. In 2001 Marks received the American Chemical Society' s Linus Pauling Medal and in 2002 the American Institute of Chemists Gold Medal.
Marks' honors also include the Burwell Award of the North American Catalysis Society, the Sir Edward Frankland Prize Lectureship of the British Royal Society of Chemistry and the Karl Ziegler Prize of the German Chemical Society. Marks is recipient of six American Chemical Society national awards and the American Chemical Society of Chicago Section's 2001 Josiah Willard Gibbs Medal, regarded by many as the highest award given to chemists, one step below the Nobel Prize. He was elected to the National Academy of Sciences and the American Academy of Arts and Sciences in 1993.
Juanary 22, 2015
ASU researchers, including Pierre Herckes, find gold in sewage sludge
Researchers at Arizona State University estimate that in a city of one million people, $13 million dollars worth of metals could be accumulating annually in sludge, the byproduct of treated sewage.
The study, which analyzed sludge from treatment centers in Arizona and samples from across the country stored at the U.S. National Biosolids Repository, focused on 13 minerals with the highest value, including gold, silver, copper, and platinum. If every bit of the metals is retrieved, researchers reported there could be $280 per ton of sludge.
"While we expected that the metals were present at low concentration, the fact that the small amounts represent such a significant economic value was definitely surprising," says Pierre Herckes, associate professor at ASU and co-author of the study. Of the $13 million, $2.6 million alone comes from gold and silver.
It' s possible that the metals found in sewage - which is basically anything that is flushed down a drain or toilet - is a result of discharge from jewelry and electronics manufacturing plants, mining, electroplating, and similar industries. After sewage is treated, 60% of the remaining sludge is spread across fields, yards, and forests throughout the country as fertilizer, with the rest sent to landfills or incinerated.
The concentration of metals in sludge, however, could pose environmental risks, so finding a way to extract them would help mitigate the effects of the gold flush - err, rush.
In 2009, a waste treatment facility in central Japan managed to extract nearly 2 kilograms of gold from the ash of incinerated sludge, which was more than the amount pulled from Japan' s Hishikari Mine, one of the world' s top gold mines.
However, no U.S. plants have started sifting through the goo just yet.
"Technically, it is possible to extract these metals, although it is very challenging," says Herckes. Currently, there is no technology we are aware of that can do it on a large scale without the use of enormous amounts of energy and harsh chemicals, he adds.
So don' t go digging out your old prospecting pan from the garage just yet. You' d have better luck scouring the streets of Manhattan' s Diamond District, where one urban prospector pulled in almost $1,000 in a week by collecting bits of gold and jewels off the ground.
read "Sewage sludge could contain millions of dollars worth of gold" in Latest News, Science
|Professors Rebekka Wachter (right), from ASU's School of Molecular Sciences, and S. Banu Ozkan, from ASU's Physics Department, discuss green fluorescent protein structures.
January 21, 2015
New mechanism unlocked for evolution of green fluorescent protein
A primary challenge in the biosciences is to understand the way major evolutionary changes in nature are accomplished. Sometimes the route turns out to be very simple. An example of such simplicity is provided in a new publication by a group of ASU scientists.
They show, for the first time, that a hinge migration mechanism, driven solely by long-range dynamic motions, can be the key for evolution of a green-to-red photoconvertible phenotype in a green fluorescent protein (GFP).
Rebekka Wachter, a professor in ASU's School of Molecular Sciences and the College of Liberal Arts and Sciences, is an expert in the field of structural characterization of GFP-like proteins. The present study is the culmination of eight years of intense effort in her laboratory.
The work, just published in the high impact journal Structure, involves collaborations with S. Banu Ozkan, from the Center for Biological Physics in the Department of Physics at ASU, and evolutionary biologist Mikhail Matz of the University of Texas.
Green fluorescent protein was first isolated from the jellyfish Aequorea victoria, which drifts with the currents off the west coast of North America. It was discovered that this protein glowed bright green under ultraviolet light. This phenomenon has found many creative applications in the biosciences.
The protein has been utilized as an extremely valuable luminous genetic tag for various biological phenomena. Using green fluorescent protein one can observe when proteins are made and where they go. This is done by joining the GFP gene to the gene of the protein of interest so that when the protein is made it will have GFP hanging off it. Since GFP fluoresces, one can shine light at the cell and wait for the distinctive green fluorescence associated with GFP to appear. The ability of some GFPs to turn red upon prolonged illumination makes them invaluable probes in super resolution fluorescence microscopy applications. This is where the current study is of most value.
To fluoresce, GFP-like proteins must adopt a compact barrel-like shape. The light-triggered red phenotype may have arisen from a common green ancestor by a reversal of firm and soft regions located in opposite corners of the beta-barrel fold.
Although six crystal structures of reconstructed ancestral Kaede-type proteins indicate that the structure is highly conserved, analysis of chain flexibility by Molecular Dynamics and perturbation response scanning, performed in the group of S. Banu Ozkan has shown that the individual flexibility of each position (i.e. structural dynamics) alters throughout the evolution of green-to-red photo conversion. Thus this study suggests that green-to-red photoconversion may have arisen from a common green ancestor by the shift of the rigid corner near the chromophore to the opposite corner of beta-barrel.
"For the first time, this work establishes a direct experimental link between protein phenotypic change and collective dynamics without any external trigger, such as substrate, product or effector binding," explains Wachter. "Based on structural, computational and kinetic data, we propose a novel photoconversion mechanism that provides a plausible path for the irreversible acquisition of red fluorescence."
In spite of intense efforts in a number of laboratories worldwide, the mechanism of photoconversion of Kaede-type proteins has remained largely enigmatic. The present work sheds light on structural, dynamic and mechanistic features that must be considered when engineering improved fluorescent probes for super-resolution microscopy applications.
ASU's School of Molecular Sciences ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry), and in the top eight nationally for research publications in the journals Science and Nature. The department's strong record in interdisciplinary research is also evidenced by its 31st national ranking by the National Science Foundation in total and federally financed higher education research and development expenditures in chemistry.
Source: Rebekka Wachter, Rebekka.Wachter@asu.edu
Jenny Green, firstname.lastname@example.org
School of Molecular Sciences
|December 04, 2014
New research paves the way for nano-movies of biomolecules
|Ray of Light:
A new generation of ultrafast X-ray lasers is redefining the field of X-ray crystallography, revealing never-before-seen features and dynamic processes.
The most powerful such instrument in its class-the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory-was used in the current study. The graphic depicts the imaging of atomic scale features of the Photoactive Yellow Protein, with brilliant bursts of light lasting mere quadrillionths of a second.
Scientists use X-ray laser as ultra slow-motion camera
An international team, including scientists from Arizona State University, the University of Milwaukee-Madison (UMW), and Germany's Deutsches Elektronen-Synchrotron (DESY), have caught a light sensitive biomolecule at work using an X-ray laser. Their new study proves that high speed X-ray lasers can capture the fast dynamics of biomolecules in ultra slow-motion, revealing subtle processes with unprecedented clarity.
"This work paves the way for movies from the nano-world with atomic resolution," said Professor Marius Schmidt from UMW, corresponding author of the new paper, which appears in the Dec. 4 issue of the journal Science.
Study co-author Petra Fromme, professor in ASU's School of Molecular Sciences, echoes the importance of the new study: "This paper is very exciting as it is the first report of time resolved studies with serial femtosecond crystallography that unravels details at atomic resolution," said Fromme. "This is a huge breakthrough toward the ultimate goal of producing molecular movies that reveal the dynamics of biomolecules with unparalleled speed and precision."
A femtosecond is a quadrillionth of a second, an almost unfathomably brief duration. Around 100 femtoseconds are required for a ray of light to traverse the width of a human hair.
The technique of X-ray crystallography allows researchers to probe atomic and molecular structure, by exposing crystals to incident X-rays that diffract from the sample in various directions. Careful measurement of X-ray diffraction angles and intensities allows a three-dimensional portrait of electron densities to be constructed-information used to define atomic structure.
The technique has been an invaluable tool for investigating the structure and function of a broad range of biologically important molecules, including drugs, vitamins, proteins and nucleic acids like DNA.
But just as shutter speed determines a camera's ability to capture action of very short duration, so X-ray lasers must deliver extremely brief pulses of light to capture fine structure and dynamic processes at the atomic level. Some of the phenomena researchers wish to explore take place in mere quadrillionths of a second. A new generation of ultrafast lasers like the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory (used in the current study) are redefining the field of X-ray crystallography.
The researchers used the photoactive yellow protein (PYP) as a model system. PYP is a receptor for blue light that is part of the photosynthetic machinery in certain bacteria. When it catches a blue photon, it cycles through various intermediate structures as it harvests the energy of the photon, before returning to its initial state. Most steps of this PYP photocycle have been well studied, making it an excellent candidate for validating a new method.
For their ultrafast snapshots of PYP dynamics, the scientists first produced tiny crystals of PYP molecules, most measuring less than 0.01 millimeters across. The dynamics of these microcrystals were captured in exquisite detail when the world's most powerful X-ray laser at SLAC was trained on them. Initiation of their photocycle was triggered with a precisely synchronised blue laser pulse.
Thanks to the incredibly short and intense X-ray flashes of the LCLS, the researchers could observe different steps in the PYP photocycle with a resolution of 0.16 nanometers, by taking snapshots of X-ray diffraction patterns. The spectacular time resolution afforded by the technique allows researchers to detect changes in the atomic-scale conformation of PYP molecules as they switch back and forth between light and dark states.
The investigation not only reproduced what was already known about the PYP photocycle, thereby validating the new method, it also imaged delicate phenomena in much finer detail. Thanks to the high temporal resolution, the X-ray laser could in principle study steps in the cycle that are shorter than 1 picosecond (a trillionth of a second) - too fast to be captured with previous techniques. The ultrafast snapshots can be assembled into a movie, detailing the dynamics in ultra slow-motion.
"This is far more than a proof of concept for time resolved crystallography. LCLS can use micron size crystals and therefore have an unmatched light initiation efficiency to explore uncharted territory in the dimension of time resolution of molecular reactions," Raimund Fromme stated, an ASU associate research professor participating in this project.
"This is a real breakthrough," emphasizes co-author professor Henry Chapman from DESY. "Our study is opening the door for time resolved studies of dynamic processes, providing an unprecedented window on subtle transformations at the atomic scale."
John Spence, director of science for the STC at ASU, stresses the importance of studying delicate life processes by means of new tools capable of extreme spatial and temporal resolution:
"When combined with previous work, it is remarkable now to be able to assemble a true molecular movie of the photocycle of this blue light detector in bacteria at atomic resolution, with the intermediate structures appearing and fading in the correct sequence. It is a huge step forward, which will also aid research on artificial photosynthesis," he says. "It builds on our earlier work at LCLS, and is supported by our NSF Science and Technology Center for the use of X-ray lasers in biology."
The new research advances the ASU team's pre-existing investigations, highlighting the first time-resolved serial femstosecond crystallography studies on Photosystem II. The study on PYP now shows that this method can unravel previously undetected details at the atomic level.
The ASU team involved in this study includes four faculty and their research teams (John Spence, Uwe Weierstall, Petra Fromme and Raimund Fromme) from the Departments of Physics and Chemistry and Biochemistry who are members of the new Center for Applied Structural Discovery at the Biodesign Institute. The ASU team contributed to many aspects of the study, which range from experimental planning to the application of injector technology, growth and biophysical characterization of the PYP microcrystals and data evalution.
The ASU team also includes the graduate students Christopher Kupitz,Chelsie Conrad, Jesse Coe, Shatabdi Roy-Chowdhury, who worked on the growth and biophysical characterization of the PYP crystals at ASU and on site at LCLS, the graduate students Daniel James and Dingjie Wang, who worked on sample delivery as well as the research scientist Nadia Zatsepin and the graduate student Shibom Basu, who worked on "on the fly" data evaluation.
"Since the sample injector developed at ASU allows for continuous sample replenishment, the X-ray laser always probes fresh, undamaged crystals, allowing us to make molecular movies of irreversible reactions," says Research Professor Uwe Weierstall. Further, X-ray lasers typically investigate very small crystals that often are much easier to fabricate than larger crystals. In fact, some biomolecules are so hard to crystallise that they can only be investigated with an X-ray laser.
"This is the highest resolution X-ray laser dataset we've worked with - these tiny crystals were of very high quality," adds research scientist Nadia Zatsepin. "It was very satisfying to see such high resolution electron densities by the second day of our experiment, but to then also see such strong signals from the changes in the structure was even more exciting,"
The small crystal size is also an advantage when it comes to kick-starting molecular dynamics uniformly across the sample. In larger samples, the initiating optical laser pulse is often quickly absorbed in the sample, which excites only a thin layer and leaves the bulk of the crystal unaffected.
he PYP microcrystals were perfectly matched to the optical absorption so that the entire crystal was undergoing dynamics, which in turn allows sensitive measurements of the molecular changes by snapshot X-ray diffraction.
Taken together, X-ray laser investigations can offer previously inaccessible insights into the dynamics of the molecular world, complementing other methods. Using the ultra slow-motion, the scientists next plan to elucidate the fast steps of the PYP photocycle that are too short to be seen with previous methods.
In the future, ultrafast laser crystallography promises to illuminate a broad range of biomolecules, from light sensitive photoreceptors to other vital proteins.
Written by: Richard Harth
Science Writer: Biodesign Institute
"Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein"; Jason Tenboer et al.; Science, 2014; DOI: 10.1126/science.1259357
Petra Fromme (480-326-7840) mobile phone
Nadia Zatsepin (480 727 6444) office
ASU Press contact
Biodesign Institute at ASU
Researchers involved in the study:
Jason Tenboer,1 Shibom Basu,2 Nadia Zatsepin,3 Kanupria Pande,1
Despina Milathianaki,4 Matthias Frank,5 Mark Hunter,5 Sébastien Boutet,4
Garth J. Williams,4 Jason E. Koglin,4 Dominik Oberthuer,6 Michael Heymann,6
Christopher Kupitz,2 Chelsie Conrad,2 Jesse Coe,2 Shatabdi Roy-Chowdhury,2
Uwe Weierstall,3 Daniel James,3 Dingjie Wang,3 Thomas Grant,7 Anton Barty,6
Oleksandr Yefanov,6 Jennifer Scales,1 Cornelius Gati,6 Carolin Seuring,6
Vukica Srajer,8 Robert Henning,8 Peter Schwander,1 Raimund Fromme,2
Abbas Ourmazd,1 Keith Moffat,8,9 Jasper Van Thor,10 John H. C. Spence,3
Petra Fromme,2 Henry N. Chapman,6 Marius Schmidt1*
1Physics Department, University of Wisconsin, Milwaukee, WI
53211, USA. 2School of Molecular Sciences,
Arizona State University, Tempe, AZ 85287, USA. 3Department
of Physics, Arizona State University, Tempe, AZ 85287, USA.
4Linac Coherent Light Source, SLAC National Accelerator
Laboratory, Sand Hill Road, Menlo Park, CA 94025, USA.
5Lawrence Livermore National Laboratory, Livermore, CA 94550,
USA. 6Center for Free Electron Laser Science, Deutsches
Elektronen Synchrotron DESY, Notkestrasse 85, 22607
Hamburg, Germany. 7Hauptman-Woodward Institute, State
University of New York at Buffalo, 700 Ellicott Street, Buffalo,
NY 14203, USA. 8Center for Advanced Radiation Sources,
University of Chicago, Chicago, IL 60637, USA. 9Department of
Biochemistry & Molecular Biology and Institute for Biophysical
Dynamics, University of Chicago, Chicago, IL 60637, USA.
10Faculty of Natural Sciences, Life Sciences, Imperial College,
London SW7 2AZ, UK.
"Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein" Science 5 December 2014:
Vol. 346 no. 6214 pp. 1242-1246 DOI: 10.1126/science.1259357
November 20, 2014
Asteroid impacts on Earth make structurally bizarre diamonds, say ASU scientists
|Diamond grains from the Canyon Diablo meteorite. The tick marks are spaced one-fifth of a millimeter (200 microns) apart.
Photo by: Arizona State University/Laurence Garvie
Scientists have argued for half a century about the existence of a form of diamond called lonsdaleite, which is associated with impacts by meteorites and asteroids. A group of scientists based mostly at Arizona State University now show that what has been called lonsdaleite is in fact a structurally disordered form of ordinary diamond.
The scientists' report is published in Nature Communications, Nov. 20, by Péter Németh, a former ASU visiting researcher (now with the Research Centre of Natural Sciences of the Hungarian Academy of Sciences), together with ASU's Laurence Garvie, Toshihiro Aoki and Peter Buseck, plus Natalia Dubrovinskaia and Leonid Dubrovinsky from the University of Bayreuth in Germany. Buseck and Garvie are with ASU's School of Molecular Sciences and School of Earth and Space Exploration, while Aoki is with ASU's LeRoy Eyring Center for Solid State Science.
"So-called lonsdaleite is actually the long-familiar cubic form of diamond, but it's full of defects," says Péter Németh. These can occur, he explains, due to shock metamorphism, plastic deformation or unequilibrated crystal growth.
The lonsdaleite story began almost 50 years ago. Scientists reported that a large meteorite, called Canyon Diablo after the crater it formed on impact in northern Arizona, contained a new form of diamond with a hexagonal structure. They described it as an impact-related mineral and called it lonsdaleite, after Dame Kathleen Lonsdale, a famous crystallographer.
Since then, "lonsdaleite" has been widely used by scientists as an indicator of ancient asteroidal impacts on Earth, including those linked to mass extinctions. In addition, it has been thought to have mechanical properties superior to ordinary diamond, giving it high potential industrial significance. All this focused much interest on the mineral, although pure crystals of it, even tiny ones, have never been found or synthesized. That posed a long-standing puzzle.
The ASU scientists approached the question by re-examining Canyon Diablo diamonds and investigating laboratory samples prepared under conditions in which lonsdaleite has been reported.
Using the advanced electron microscopes in ASU's Center for Solid State Science, the team discovered, both in the Canyon Diablo and the synthetic samples, new types of diamond twins and nanometer-scale structural complexity. These give rise to features attributed to lonsdaleite.
"Most crystals have regular repeating structures, much like the bricks in a well-built wall," says Peter Buseck. However, interruptions can occur in the regularity, and these are called defects. "Defects are intermixed with the normal diamond structure, just as if the wall had an occasional half-brick or longer brick or row of bricks that's slightly displaced to one side or another."
The outcome of the new work is that so-called lonsdaleite is the same as the regular cubic form of diamond, but it has been subjected to shock or pressure that caused defects within the crystal structure.
One consequence of the new work is that many scientific studies based on the presumption that lonsdaleite is a separate type of diamond need to be re-examined. The study implies that both shock and static compression can produce an intensely defective diamond structure.
The new discovery also suggests that the observed structural complexity of the Canyon Diablo diamond results in interesting mechanical properties. It could be a candidate for a product with exceptional hardness.
The School of Earth and Space Exploration is an academic unit of ASU's College of Liberal Arts and Sciences.
Robert Burnham, email@example.com
Mars Space Flight Facility
"Lonsdaleite is faulted and twinned cubic diamond and does not exist as a discrete material", Péter Németh, Laurence A. J. Garvie, Toshihiro Aoki, Natalia Dubrovinskaia, Leonid Dubrovinsky & Peter R. Buseck, Nature Communications 5, Article number: 5447, doi:10.1038/ncomms6447, 20 November 2014
November 19, 2014
New award accelerates Biodesign's efforts in synthetic biology
A new four-year, multi-million dollar award from the Defense Advanced Research Projects Agency or DARPA will be used to develop the technology necessary to synthesize, screen, and sequence artificial genetic polymers composed of threose nucleic acid (TNA).
John Chaput, a professor in the School of Molecular Sciences and research investigator in the Biodesign Institute will lead ASU's effort to evolve TNA molecules that fold into novel 3D shapes with ligand binding affinity and catalytic activity.
Professor Chaput is joined by ASU colleague Wade Van Horn, PhD, School of Molecular Sciences as well as Martin Egli, PhD, Department of Biochemistry at Vanderbilt University, and Jennifer Heemstra, PhD, Department of Chemistry, University of Utah.
The research is part of a new DARPA program called Folded Non-Natural Polymers with Biological Function (Fold F(x)), which plans to use synthetic polymers to address rapidly emerging health and defense threats.
Naturally occurring biopolymers like DNA, RNA, and proteins are limited to functions that are required to sustain life, and prone to degradation by metabolic pathways that recycle biomolecules for other purposes. Recognizing these limitiations, researchers would like to design new types of synthetic polymers, with versatile functions and folding motifs, that are stable to biological and harsh environmental conditions.
"This project integrates chemistry with molecular biology and genetics to produce synthetic molecules with tailor-made activities,"Chaput says.
The group's project is based on Chaput's efforts to develop TNA as an artificial genetic polymer that is capable of heredity and evolution. This requires using organic chemistry to synthesize TNA monomers that are not commercially available and engineering DNA polymerases to copy genetic information back and forth between TNA and DNA.
By introducing a selective amplification step into the replication cycle, like the ability to bind a small molecule target or catalyze a chemical reaction, large combinatorial pools can be searched for TNA molecules with desired functional properties.
This process is analogous to natural selection, where deleterious traits are removed from the population through iterative rounds of selection and amplification. In the case of TNA, molecules that meet the selective challenge will be recovered and amplified to generate progeny molecules that increase in abudance.
Affinity reagents, like those under development, may prove invaluable for biomedical applications. Their strength lies in their foreignness. Most diagnostic tests currently use antibodies as the affinity reagent. However, antibodies are not stable to heating, and can be degraded by enzymes present in biological samples.
In contrast, TNA affinity reagents are expected to remain functional after heating and cooling, and biological systems have not developed the kinds of enzymes necessary to recognize and degrade these synthetic polymers. A key aspect of the project is new technology that will quickly generate affinity reagents capable of converting the presence of a specific molecule into an optical signal. Heemstra says "Directly selecting for TNA affinity reagents that have the desired optical output will enable us to rapidly respond to emerging threats."
The team plans to determine the 3D structure of functional TNA molecules isolated by in vitro selection. Dr. Egli will head the X-ray crystallography experiments and Dr. Van Horn the nuclear magnetic resonance (NMR) spectroscopy efforts. Understanding the structural architecture of TNA is an important part of the overall project because very little is known about the atomic organization of TNA. Structural information gained from these studies will allow scientists to understand how unnatural polymers, like TNA, fold into globular structures.
"Since TNA has a different backbone than DNA and RNA, it will be interesting to learn what shapes these molecules can adopt. This structural information will help us to understand how TNA molecules perform more complex functions as biosensors and catalysts,"Van Horn says.
The new project will also introduce modified bases into TNA molecules. The combination of altered bases and threose backbone may yield novel folding geometries, with as-yet unknown functional properties, potentially allowing nucleotides to perform in a manner similar to proteins.
The technical challenges involved in the current project are formidable, and therefore consistent with the high-risk high-reward model of DARPA-funded research. The team hopes the synthetic biology initiative will be a springboard for new ideas and techniques to be exploited by other labs and in time, brought to the forefront of molecular biology.
Written by: Richard Harth
Science Writer: Biodesign Institute
November 6, 2014
Peter G. Schultz to give Fall Eyring Lectures
November 13 and 14, 2014
Peter G. Schultz
Professor of Chemistry, The Scripps Research Institute, La Jolla, CA
"An Expanding Genetic Code"
6:30 PM, PSH-152
"A Chemist's Foray intoTranslational Research"
3:40 PM, PSH-151
Peter G. Schultz graduated summa cum laude from Caltech in 1979 and continued there for his doctoral degree (in 1984) with Professor Peter Dervan. He then spent a year at the Massachusetts Institute of Technology with Professor Christopher Walsh before moving to the University of California, Berkeley, and the Howard Hughes Medical Institute. He is currently the Scripps Professor of Chemistry at the Scripps Research Institute. Schultz has made a number of major contributions to science including the discovery of catalytic antibodies, methodology that for the first time expands the genetic codes of living organisms, and the development and application of combinatorial methods in chemistry and biology including the first generation of combinatorial materials libraries. Schultz also established the Genomics Institute of the Novartis Research Foundation in 1999 in La Jolla (and served as its Director until 2010 with some 600 FTE), which develops and applies state of the art high throughput chemical, proteomics, genomics and informatics technologies to the development of new human therapeutics. More recently, Schultz has established a not for profit institute, the California Institute for Biomedical Research (Calibr), that is focused on early stage translational research to create innovative medicines for major unmet medical needs. Schultz is the author of 500+ scientific publications, has trained over 300 coworkers and has received numerous awards including the Alan T. Waterman Award, NSF (1988), the ACS Award in Pure Chemistry (1990), the Wolf Prize in Chemistry (1994), the Paul Erhlich and Ludwig Darmstaedter Award (2002), the ACS Arthur C. Cope Award (2006), and the Solvay Prize (2013). Professor Schultz is a member of the National Academy of Sciences, USA (1993) and the Institute of Medicine of the National Academy of Sciences (1998) and he is active on many editorial and scientific advisory boards. He is a founder of Affymax Research Institute, Symyx Technologies, Syrrx, Kalypsys, Phenomix, Ilypsa, Ambrx, Wildcat Discovery Technologies, and Ardelyx, which have pioneered the application of molecular diversity technologies to challenges in energy, materials and human health.
October 22, 2014
ASU grant aims to transform global energy landscape
Changing the way the nation generates and consumes energy is at the heart of a multimillion dollar grant awarded to Arizona State University from the Department of Energy.
Under the grant, the university will develop an efficient and cost-effective carbon capture technology using an innovative electrochemical technique to separate carbon dioxide from other emissions originating from power plants.
In what could be an economically enabling breakthrough in the drive to reduce carbon emissions, ASU researchers will explore the real possibility of reducing energy and cost requirements by more than half.
Led by Dan Buttry, professor and chair of ASU's School of Molecular Sciences in the College of Liberal Arts and Sciences, the grant is part of a special Department of Energy program designed to pursue high-risk, high-reward advances in alternative energy research.
"Through this type of venture we are working to advance research and spur economic development in the areas of renewable energy and energy security to create solutions that address society's grand challenges," said Sethuraman "Panch" Panchanathan, senior vice president for ASU's Office of Knowledge Enterprise Development. "This innovative project is a collaborative effort of faculty at ASU from multiple disciplines, as well as collaborators from Proton OnSite and the University of Colorado, who are all developing a new carbon capture technology."
Jenny Green, firstname.lastname@example.org
Where solutions happen
Arizona State University has been building its portfolio in alternative energy research for several years, and currently includes among its capabilities a center for research into electrochemistry for renewable energy applications; several advanced programs on solar energy research; one of the leading testing and certification centers for solar energy; and research into solar-generated biofuels, including advanced work on algae-based biofuels.
The university's awarded grant of $2.9 million over two years follows an initial "seed" grant where the team demonstrated proof of concept of efficient and cost-effective carbon dioxide capture. ASU's project was selected through a merit-based process from thousands of concept papers and hundreds of full applications.
The projects are based in 24 states, with approximately 47 percent of the projects led by universities - all supported by the Department of Energy's Advanced Research Projects Agency-Energy (ARPA-E) program, which aims to develop clever and creative approaches to transform the global energy landscape while advancing America's technology leadership.
Inspired by the Defense Advanced Research Projects Agency, ARPA-E was created to support high-risk, high-reward research that can provide transformative new solutions for climate change and energy security.
"The potential of this project to advance solutions to the problem of excessive carbon dioxide in the environment is exciting, and we look forward to the team's progress in this area," said Gary Dirks, director of ASU LightWorks. "ASU is a place where the convergence of laboratory research and real-world application creates a unique environment where imaginative energy-related projects are fostered and encouraged."
A new approach
The carbon capture program was initially supported by ASU LightWorks, which brings together the intellectual expertise across the university centered on leveraging the power of the sun to create solutions in the areas of renewable energy, including generating electricity, alternative fuels and preparing future energy leaders.
"We are extremely excited about this new grant from the Department of Energy ARPA-E program," said Buttry. "The effort is focused on a key issue in fossil fuel-based energy production - how to reduce atmospheric carbon dioxide emissions without consuming too much of the energy content of the fuel. We have recently developed a new approach to carbon dioxide capture that uses an electrochemical process with some design features similar to those in a fuel cell."
Co-principal investigators on this project are Cody Friesen, SEMTE-Ira A. Fulton Schools of Engineering; Vladimiro Mujica, School of Molecular Sciences; and Ellen Stechel, School of Molecular Sciences and also deputy director of LightWorks. Buttry and Friesen previously worked on an ARPA-E project developing a radical new design for automotive batteries.
Mujica will use quantum chemical calculations to help understand the binding of carbon dioxide to the carrier compounds. Stechel is simulating the cell behavior, Friesen's group is working on cell design, and Buttry's on the chemistry and electrochemistry of the binding process.
Also collaborating on this grant are two researchers from the University of Colorado, Boulder; Doug Gin, in chemistry, and Rich Noble, in chemical engineering, who are helping to make very thin membranes for the separation process. Katherine Ayers of Proton OnSite, CT, will be involved with cell design and engineering.
The only proven commercially viable technology for flue gas capture uses compounds called amines in the so-called monoethanolamine (MEA) process. Several plant scale demonstrations use this old technology, first patented in 1930. The MEA process has several drawbacks, particularly the energy required for thermal regeneration of the amine capture agent. As discussed in a recent Department of Energy report (DOE/NETL-2009/1366), for typical conditions, the energy required for this process consumes roughly 40 percent of total plant output, and increases the cost of electricity by 85 percent.
Buttry predicts their innovative approach as having an overall efficiency far better than existing efforts.
ASU's School of Molecular Sciences ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry), and in the top eight nationally for research publications in the journals Science and Nature. The department's strong record in interdisciplinary research is also evidenced by its 31st national ranking by the National Science Foundation in total and federally financed higher education research and development expenditures in chemistry.
School of Molecular Sciences
ASU scientist Devens Gust receives Lifetime Achievement Award
Devens Gust, a scientist in the School of Molecular Sciences at Arizona State University has recently been awarded with the 2014 Hans Fischer Lifetime Achievement Award in Porphyrin Chemistry by the Society of Porphyrins and Phthalocyanines.
This international award is sponsored by the Hans Fischer Gesellschaft in Munich, named for Hans Fischer, a German organic chemist and 1930 recipient of the Nobel Prize in Chemistry. The award is given every two years to a senior scientist for his or her lifetime work in the field of porphyrins and phthalocyanines.
Gust is an internationally recognized expert in the areas of photochemistry and artificial photosynthesis. He is the director of the Energy Frontier Research Center for Bio-Inspired Solar Fuel Production at ASU and a past director of the Center for the Study of Early Events in Photosynthesis in the College of Liberal Arts and Sciences. He is also a fellow of both the American Association for the Advancement of Science and the Institute of Physics in the U.K.
The award was recently presented to Gust by Hugo Scheer, professor of biology at Ludwig-Maximillian University, Munich, Germany, at the International Conference on Porphyrins and Phthalocyanines in Istanbul, Turkey.
It was given to Gust for his incisive research over four decades on porphyrins and similar materials. Porphyrins and their relatives include chlorophyll, which is a major pigment in photosynthesis; heme, which is the oxygen carrier in our blood and important in biological energy flow; phthalocyanines, which are used as dyes in compact discs, in molecular electronics and many compounds for photomedicine. Most of Gust's work has employed porphyrins as components of artificial photosynthetic systems for conversion of sunlight into energy in the form of electricity or, alternatively, stored in chemical fuels such as hydrogen.
Gust has produced over 300 publications in top journals, made 17 patents and has been rewarded with a continuous stream of invitations to keynote at international conferences, and to deliver named lectures across the world.
"He and his colleagues have truly established ASU as a world center of excellence in the area of artificial photosynthesis," says Regents' Professor Austen Angell. "ASU is on the international science map because of them."
Devens explained best in his own words, "I came to ASU because Mort Munk convinced me that the university had great opportunities for growth and improvement and was on an upward trajectory. Mort was right, and I have never regretted remaining here for my entire career. I have been very lucky to have many great colleagues in the department, including my long-time research collaborators Tom and Ana Moore, and my associate chair Seth Rose. Much of what I have accomplished is due to them and to my wonderful research students. I look forward to continuing an active research program and my association with the department."
"We are delighted by this award to Devens," says Regents' Professor and colleague Ana Moore. "It is our good fortune to be able to collaborate with him. He is always a source of good ideas, critical thinking and his laser-like focus on the goals at hand keeps us from drifting."
The Society of Porphyrins and Phthalocyanines was formed in June 2000 and serves the interests of scientists working in those areas and related fields, but come from a broad variety of scientific disciplines
New method of detecting bone loss could help predict disease progression
A team of researchers from Arizona State University and Mayo Clinic is showing how a staple of earth science research can be used in biomedical settings to predict the course of disease.
The researchers tested a new approach to detecting bone loss in cancer patients by using calcium isotope analysis to predict whether myeloma patients are at risk for developing bone lesions, a hallmark of the disease.
They believe they have a promising technique that could be used to chart the progression of multiple myeloma, a lethal disease that eventually impacts a patient's bones. The method could help tailor therapies to protect bone better and also act as a way to monitor for possible disease progression or recurrence.
"Multiple myeloma is a blood cancer that can cause painful and debilitating bone lesions," said Gwyneth Gordon, an associate research scientist in ASU's School of Earth and Space Exploration and co-lead author of the study. "We wanted to see if we could use isotope ratio analysis, a common technique in geochemistry, to detect the onset of disease progression."
"At present, there is no good way to track changes in bone balance except retrospectively using X-ray methods," said Ariel Anbar, a President's Professor in ASU's School of Earth and Space Exploration and the School of Molecular Sciences. "By the time the X-rays show something, the damage has been done."
"Right now, pain is usually the first indication that cancer is affecting the bones," added Rafael Fonseca, chair of the Department of Medicine at the Mayo Clinic and a member of the research team. "If we could detect it earlier by an analysis of urine or blood in high-risk patients, it could significantly improve their care," he added.
The research team-which includes Gordon, Melanie Channon and Anbar from ASU, as well as Jorge Monge (co-lead author), Qing Wu and Fonseca from Mayo Clinic-described the tests and their results in "Predicting multiple myeloma disease activity by analyzing natural calcium isotopic composition," in an early online edition (July 9) of the Nature publication Leukemia.
The technique measures the naturally occurring calcium isotopes that the researchers believe can serve as an accurate, near-real-time detector of bone metabolism for multiple myeloma patients. Bone destruction in myeloma manifests itself in bone lesions, osteoporosis and fractures. The ASU-Mayo Clinic work builds on a previous NASA study by the ASU team. That research focused on healthy subjects participating in an experiment.
"This is the first demonstration that the technique has some ability to detect bone loss in patients with disease," said Anbar, a biogeochemist at ASU.
With the method, bone loss is detected by carefully analyzing the isotopes of calcium that are naturally present in blood. Isotopes are atoms of an element that differ in their masses. Patients do not need to ingest any artificial tracers, and are not exposed to any radiation for the test. The only harm done with the new method, Anbar said, is a pinprick for a blood draw.
The technique makes use of a fact well-known to earth scientists but not normally used in biomedicine-different isotopes of a chemical element can react at slightly different rates. The earlier NASA study showed that when bones form, the lighter isotopes of calcium enter bone a little faster than the heavier isotopes. That difference, called isotope fractionation, is the key to the method.
In healthy, active humans, bone is in "balance," meaning bone is forming at about the same rate as it dissolves (resorbs). But if bone loss is occurring, then the isotopic composition of blood becomes enriched in the lighter isotopes as bones resorb more quickly than they are formed.
The effect on calcium isotopes is very small, typically less than a 0.02 percent change in the isotope ratio. But even effects that small can be measured by using precise mass spectrometry methods available at ASU. With the new test, the ASU-Mayo Clinic researchers found that there was an association between how active the disease was and the change in the isotope ratios. In addition, the isotope ratios predicted disease activity better than, and independent from, standard clinical variables.
Anbar said that while the method has worked on a small set of patients, much still needs to be done to verify initial findings and improve the efficiency of analysis.
"If the method proves to be robust after more careful validation, it could provide earlier detection of bone involvement than presently possible, and also provide the possibility to monitor the effectiveness of drugs to combat bone loss."
- See more at: http://researchmatters.asu.edu/stories/new-method-detecting-bone-loss-could-help-predict-disease-progression-3432#sthash.vi1zDGOy.dpuf
by Skip Derra
|Arizona State University professor Petra Fromme
Credit: Glenn Roberts Photo courtesy SLAC National Acc
August 1, 2014
New ASU center to expand cutting-edge research
African sleeping sickness infects an estimated 20,000 people a year and is almost always fatal if untreated.
Diagnosis is complex. The drugs used to treat the illness can have serious side effects.
But a breakthrough discovery a few years ago using cutting-edge X-ray technology revealed a weak spot, an enzyme, in the parasite that causes the disease.
The finding, by an international team of researchers that included Arizona State University professor Petra Fromme, could make it possible to develop new drugs to inhibit the enzyme so humans can't be infected.
The finding was one of several research projects Fromme was involved in over the past decade. Now, her work will be expanding as the university launches a new research center under her leadership.
"We will build upon the progress we've made," Fromme said in an interview with The Arizona Republic.
The Center for Applied Structural Discovery will use powerful X-ray lasers to examine the tiny molecular structures that carry out chemical reactions in cells.
If scientists know how these structures function at the microscopic level, they can change, tweak or design new functions that could possibly lead to developing new drugs that work with proteins within the cells to fight cancer and infectious disease.
ASU Provost Robert Page describes the work already done by ASU researchers in this area as cutting-edge science.
"If there is going to be a Nobel Prize from ASU scientists, this is at the top of the list of potential Nobel-level research," he said.
The center is part of ASU's Biodesign Institute, a signature research initiative under ASU President Michael Crow that focuses on biomedicine and health, sustainability and security. In a statement, Crow said Fromme's research promises to crack nature's code and replicate fundamental biological processes, such as photosynthesis, for "profound societal benefits."
ASU plans to build a new center housing the lab and the next generation of X-ray technology.
Research centers enable scientists from different academic backgrounds to work together to solve common problems. The centers rely on grant funding and often involve researchers from other universities.
In the case of the new ASU center, researchers in physics and biochemistry are already working together with an international team. A half-dozen new researchers will be hired. The benefits of a new center will trickle down to undergraduates, who will be able to take part in the research.
Fromme said that when researchers first suggested the X-ray technique several years ago, it was difficult to get grant funding. Many believed it would fail. The team pushed ahead anyway. It would meet every Friday for two hours to brainstorm, and its efforts began to pay off.
In 2012, the journal Science cited the team's research using X-rays as one of the top 10 breakthroughs of the year. ASU researchers, as part of an international team, were able to determine for the first time the three-dimensional structure of a protein using X-ray lasers.
In layman's terms, that is the difference between having short movies of a horse running vs. photographs of the horse.
"It has so many applications," Fromme said of the research. "It's a completely new kind of endeavor."
More recently, Fromme was the senior author and leader of an international team that published a paper in Nature in July on using X-ray laser technology to capture the first snapshots of photosynthesis as it split water into protons, electrons and oxygen.
Plants use photosynthesis to convert light energy into chemical energy that can be released later. The process is key to maintaining the planet's oxygen.
The finding could be used in efforts at ASU to create an "artificial leaf" that is similar or surpasses the function of natural leaves.
Fromme is from Germany and has a doctoral degree in chemistry. She was an associate professor at Technical University Berlin before coming to ASU in 2002.
ASU officials say she is a highly sought-after researcher because of her discoveries, and other scientists have tried to lure her away from ASU. The new center at ASU will allow Fromme to expand her work and keep her at the university.
Funding for the team's research comes from a variety of sources, including the U.S. Department of Energy, the National Institutes of Health, the National Science Foundation and the German Research Foundation, among others.
For now, the center will be headquartered in a wing of the George M. Bateman Physical Sciences Center on the Tempe campus. But ASU officials have already started discussions about additional space.
"This will be one of our more exciting projects," said Rich Stanley, the university's senior vice president and planner.
Links to some of Petra Fromme's research:
African sleeping sickness:
Top 10 science breakthroughs 2012:
What is X-ray crystallography?
ASU Professor Petra Fromme is a leading researcher in X-ray crystallography.Scientists use ultra-fast X-ray pulses to examine structures of molecular systems, such as proteins involved in photosynthesis.
Fromme uses the world's most powerful X-ray laser, the Linac Coherent Light Source, better known as LCLS. The laser is at the U.S. Department of Energy's SLAC National Accelerator Laboratory at Stanford University.
The laser works like a high-speed camera, allowing pictures of atoms and molecules in motion. This allows scientists to have a better look at the fundamental processes of life.
Anne Ryman, The Republic
SLAC National Accelerator Laboratory
Jenny Green, email@example.com
School of Molecular Sciences
|A team of ASU researchers has demonstrated that a particular mineral, sphalerite, can affect the most fundamental process in organic chemistry: carbon-hydrogen bond breaking and making. This is a sample of gem-quality sphalerite in a quartz matrix.
Credit: Tom Sharp
|This photograph of a drill core sample from the Nankai Trough Hydrothermal system near Japan contains sphalerite grains. This mineral typically has a black crystalline structure.
Credit: Hilairy Hartnett
|For their experiments, the team needed high pressures and high temperatures in a chemically inert container. To get these conditions, the reactants are welded into a pure gold capsule and placed in a pressure vessel, inside a furnace. When an experiment is done, the gold capsule is frozen in liquid nitrogen to stop the reaction, opened and allowed to thaw while submerged in dichloromethane to extract the organic products.
Credit: Jessie Shipp
July 28, 2014
ASU team shows evidence for one mineral affecting the most fundamental process in organic chemistry: carbon-hydrogen bond breaking and making
Reactions among minerals and organic compounds in hydrothermal environments are critical components of the Earth's deep carbon cycle, they provide energy for the deep biosphere, and may have implications for the origins of life. However, very little is known about how minerals influence organic reactions. A team of researchers from Arizona State University have demonstrated how a common mineral acts as a catalysts for specific hydrothermal organic reactions - negating the need for toxic solvents or expensive reagents.
At the heart of organic chemistry, aka carbon chemistry, is the covalent carbon-hydrogen bond (C-H bond) — a fundamental link between carbon and hydrogen atoms found in nearly every organic compound.
The essential ingredients controlling chemical reactions of organic compounds in hydrothermal systems are the organic molecules, hot pressurized water, and minerals, but a mechanistic understanding of how minerals influence hydrothermal organic reactivity has been virtually nonexistent.
The ASU team set out to understand how different minerals affect hydrothermal organic reactions and found that a common sulfide mineral (ZnS, or Sphalerite) cleanly catalyzes a fundamental chemical reaction - the making and breaking of a C-H bond.
Their findings are published in the July 28 issue of the Proceedings of the National Academy of Sciences. The paper was written by a transdisciplinary team of ASU researchers that includes: Jessie Shipp (2013 PhD in Chemistry & Biochemistry), Ian Gould, Lynda Williams, Everett Shock, and Hilairy Hartnett. The work was funded by the National Science Foundation.
"Typically you wouldn't expect water and an organic hydrocarbon to react. If you place an alkane in water and add some mineral it's probably just going to sit there and do nothing," explains first author Shipp. "But at high temperature and pressure, water behaves more like an organic solvent, the thermodynamics of reactions change, and suddenly reactions that are impossible on the bench-top start becoming possible. And it's all using naturally occurring components at conditions that can be found in past and present hydrothermal systems."
A mineral in the mix
Previously, the team had found they could react organic molecules in hot pressurized water to produce many different types of products, but reactions were slow and conversions low. This work, however, shows that in the presence of sphalerite, hydrothermal reaction rates increased dramatically, the reaction approached equilibrium, and only one product formed. This very clean, very simple reaction was unexpected.
"We chose sphalerite because we had been working with iron sulfides and realized that we couldn't isolate the effects of iron from the effects of sulfur. So we tried a mineral with sulfur but not iron. Sphalerite is a common mineral in hydrothermal systems so it was a pretty good choice. We really didn't expect it to behave so differently from the iron sulfides," says Hartnett, an associate professor in the School of Earth and Space Exploration, and in the School of Molecular Sciences at ASU.
This research provides information about exactly how the sphalerite mineral surface affects the breaking and making of the C-H bond. Sphalerite is present in marine hydrothermal systems i.e., black smokers, and has been the focus of recent origins-of-life investigations.
For their experiments, the team needed high pressures (1000 bar - nearly 1000 atm) and high temperatures (300°C) in a chemically inert container. To get these conditions, the reactants (sphalerite, water, and an organic molecule) are welded into a pure gold capsule and placed in a pressure vessel, inside a furnace. When an experiment is done, the gold capsule is frozen in liquid nitrogen to stop the reaction, opened and allowed to thaw while submerged in dichloromethane to extract the organic products.
"This research is a unique collaboration because Dr. Gould is an organic chemist and you combine him with Dr. Hartnett who studies carbon cycles and environmental geochemistry, Dr. Shock who thinks in terms of thermodynamics and about high temperature environments, and Dr. Williams who is the mineral expert, and you get a diverse set of brains thinking about the same problems," says Shipp.
Hydrothermal organic reactions affect the formation, degradation, and composition of petroleum, and provide energy and carbon sources for microbial communities in deep sedimentary systems. The results have implications for the carbon cycle, astrobiology, prebiotic organic chemistry, and perhaps even more importantly for Green Chemistry (a philosophy that encourages the design of products and processes that minimize the use and generation of hazardous substances).
"This C-H bond activation is a fundamental step that is ultimately necessary to produce more complex molecules - in the environment those molecules could be food for the deep biosphere - or involved in the production of petroleum fuels," says Hartnett. "The green chemistry side is potentially really cool - since we can conduct reactions in just hot water with a common mineral that ordinarily would require expensive or toxic catalysts or extremely harsh - acidic or oxidizing - conditions."
Hilairy Hartnett, firstname.lastname@example.org
Jessie Shipp, email@example.com
Nikki Cassis, firstname.lastname@example.org
July 9. 2014
ASU-led study yields first snapshots of water splitting in photosynthesis
An international team, led by Arizona State University scientists, has published today in Nature a groundbreaking study that shows the first snapshots of photosynthesis in action as it splits water into protons, electrons and oxygen-the process that maintains Earth's oxygen atmosphere.
"This study is the first step towards our ultimate goal of unraveling the secrets of water splitting and obtaining molecular movies of biomolecules," said Petra Fromme, professor of chemistry and biochemistry at ASU. Fromme is the senior author and leader of the international team, which reported their work in "Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser," in the July 9 online issue of Nature.
Photosynthesis is one of the fundamental processes of life on Earth. The early Earth contained no oxygen and was converted to the oxygen-rich atmosphere we have today 2.5 billion years ago by the "invention" of the water splitting process in Photosystem II (PSII). All higher life on Earth depends on this process for its energy needs, and PSII produces the oxygen we breathe, which ultimately keeps us alive.
The revealing of the mechanism of this water splitting process is essential for the development of artificial systems that mimic and surpass the efficiency of natural systems. The development of an "artificial leaf" is one of the major goals of the ASU Center for Bio-Inspired Solar Fuel Production, which was the main supporter of this study.
"A crucial problem facing our Center for Bio-Inspired Fuel Production (Bisfuel) at ASU and similar research groups around the world is discovering an efficient, inexpensive catalyst for oxidizing water to oxygen gas, hydrogen ions and electrons," said ASU Regents' Professor Devens Gust, the center's director. "Photosynthetic organisms already know how to do this, and we need to know the details of how photosynthesis carries out the process using abundant manganese and calcium.
"The research by Fromme and coworkers gives us, for the very first time, a look at how the catalyst changes its structure while it is working," Gust added. "Once the mechanism of photosynthetic water oxidation is understood, chemists can begin to design artificial photosynthetic catalysts that will allow them to produce useful fuels using sunlight."
In photosynthesis, oxygen is produced at a special metal site containing four manganese atoms and one calcium atom, connected together as a metal cluster. This oxygen-evolving cluster is bound to the protein PSII that catalyzes the light-driven process of water splitting. It requires four light flashes to extract one molecule of oxygen from two water molecules bound to the metal cluster.
Fromme states that there are two major drawbacks to obtaining structural and dynamical information on this process by traditional X-ray crystallography. First, the pictures one can obtain with standard structural determination methods are static. Second, the quality of the structural information is adversely affected by X ray damage.
"The trick is to use the world's most powerful X-ray laser, named LCLS, located at the Department of Energy's SLAC National Accelerator Laboratory," said Fromme. "Extremely fast femtosecond (10 -15 second) laser pulses record snapshots of the PSII crystals before they explode in the X-ray beam, a principle called ‘diffraction before destruction.'"
In this way, snapshots of the process of water splitting are obtained damage-free. The ultimate goal of the work is to record molecular movies of water splitting.
The team performed the time-resolved femtosecond crystallography experiments on Photosystem II nanocrystals, which are so small that you can hardly see them, even under a microscope. The crystals are hit with two green laser flashes before the structural changes are elucidated by the femtosecond X-ray pulses.
The researchers discovered large structural changes of the protein and the metal cluster that catalyzes the reaction. The cluster significantly elongates, thereby making room for a water molecule to move in.
"This is a major step toward the goal of making a movie of the molecular machine responsible for photosynthesis, the process by which plants make the oxygen we breathe, from sunlight and water," explained John Spence, ASU Regents' Professor of physics, team member and scientific leader of the National Science Foundation-funded BioXFEL Science and Technology Center, which develops methods for biology with free electron lasers.
ASU recently made a large commitment to the groundbreaking work of the femtosecond crystallography team by planning to establish a new Center for Applied Structural Discovery at the Biodesign Institute at ASU. The center will be led by Petra Fromme.
Student role in research
An interdisciplinary team of eight ASU faculty members from the School of Molecular Sciences (Petra Fromme, Alexandra Ros, Tom Moore and Anna Moore) and the Department of Physics (John Spence, Uwe Weierstall, Kevin Schmidt and Bruce Doak) worked together with national and international collaborators on this project. The results were made possible by the excellent work of current ASU graduate students Christopher Kupitz, Shibom Basu, Daniel James, Dingjie Wang, Chelsie Conrad, Shatabdi Roy Chowdhury and Jay-How Yang, as well as ASU doctoral graduates and post-docs Kimberley Rendek, Mark Hunter, Jesse Bergkamp, Tzu-Chiao Chao and Richard Kirian.
Two undergraduate students, Danielle Cobb and Brenda Reeder, supported the team and gained extensive research experience by working hand-in-hand with graduate students, researchers and faculty at the free electron laser at Stanford. Four ASU senior scientists and postdoctoral researchers (Ingo Grotjohann, Nadia Zatsepin, Haiguang Liu and Raimund Fromme) supported the faculty in the design, planning and execution of the experiments, and were also instrumental in evaluation of the data.
The first authorship of the paper is jointly held by ASU graduate students Christopher Kupitz and Shibom Basu. Kupitz's dissertation is based on the development of new techniques for the growth and biophysical characterization of nanocrystals, and Basu devoted three years of his doctoral work to the development of the data evaluation methods.
"It is so exciting to be a part of this groundbreaking research and to have the opportunity to participate in this incredible international collaboration," said Kupitz, who will graduate this summer with a doctorate in biochemistry. "I joined the project because it fascinates me to work at the LCLS accelerator on this important biological project."
"The most exciting aspect of the work on Photosystem II is the prospect of making molecular movies to witness the water splitting process through time-resolved crystallography," added Basu.
National and international collaborators on the project include the team of Henry Chapman at DESY in Hamburg, Germany, who, with the ASU team and researchers at the MPI in Heidelberg, pioneered the new method of serial femtosecond crystallography. Other collaborators included a team led by Matthias Frank, an expert on laser spectroscopy and time-resolved studies with FELs at Lawrence Livermore National Laboratory, and the team of Yulia Pushkar at Purdue University, who supported the work with characterization of the crystals by electron paramagnetic resonance.
"We're tantalizingly close," said Chapman of the Center for Free-Electron Laser Science at DESY and a pioneer in X-ray-free laser studies of crystallized proteins. "I think this shows that we really are on the right track and it will work."
Additional collaborators include scientists from SLAC, Lawrence Berkeley National Laboratory; the Stanford PULSE Institute; Max Planck Institutes for medical research and nuclear physics; the University of Hamburg; the European X-ray Free-Electron Laser and the Center for Ultrafast Imaging; the University of Melbourne in Australia; Uppsala University in Sweden; and University of Regina in Canada.
The work was supported by the Department of Energy's Office of Science, the National Institutes of Health, the National Science Foundation, German Research Foundation (DFG), the Max Planck Society, the SLAC and Lawrence Livermore National Laboratory Directed Research and Development programs, and the BioXFEL Science and Technology Center, among others.
Petra Fromme, (480) 965-9028
Skip Derra, email@example.com
Jenny Green, firstname.lastname@example.org
School of Molecular Sciences
|Biogeochemist Ariel Anbar has been selected as Arizona State University's first Howard Hughes Medical Institute Professor. He is one of 15 professors from 13 universities whose appointments were announced by the Maryland-based biomedical research institute on June 30. The appointment includes a five-year, $1 million grant to support Anbar's research and educational activities.
Photo by: Nathaniel Anbar
July 1, 2014
ASU faculty member named Howard Hughes Medical Institute Professor
Biogeochemist Ariel Anbar has been selected as Arizona State University's first Howard Hughes Medical Institute Professor. This distinguished honor recognizes Anbar's pioneering research and teaching.
He is one of 15 professors from 13 universities whose appointments were announced by the Maryland-based biomedical research institute on June 30. The appointment includes a five-year, $1 million grant to support Anbar's research and educational activities.
Since the inception of the institute's professor program in 2002, and including the new group of 2014 professors, only 55 scientists have been appointed Howard Hughes Medical Institute professors. These professors are accomplished research scientists who are working to change undergraduate science education in the United States.
"Exceptional teachers have a lasting impact on students," said Robert Tjian, Howard Hughes Medical Institute president. "These scientists are at the top of their respective fields, and they bring the same creativity and rigor to science education that they bring to their research."
Anbar, a professor in ASU's School of Earth and Space Exploration and the School of Molecular Sciences in the College of Liberal Art and Sciences, as well as a Distinguished Sustainability Scientist in the Global Institute of Sustainability, was named an ASU President's Professor in 2013 in recognition of his pioneering online education efforts. He is deeply involved in using the medium to its fullest to help educate and encourage a generation that has grown up with the Internet.
A leading geoscientist with more than 100 peer-reviewed papers to his name, Anbar's research focuses on Earth's past and future as a habitable planet. This expertise feeds directly into his teaching in the highly successful class "Habitable Worlds," developed through ASU Online. In "Habitable Worlds," Anbar and course designer Lev Horodyskyj combine the power of the Internet, game-inspired elements and the sensibilities of a tech-savvy generation to teach what makes planets habitable and engage students in a simulated hunt for other habitable worlds in the cosmos. This innovative online course kindles student interest and learning. Beginning in fall 2014, it will be available outside of ASU as "HabWorlds Beyond," via a partnership with education technology company Smart Sparrow. "Habitable Worlds" has been taken by more than 1,500 ASU students and consistently receives outstanding student reviews.
The Howard Hughes Medical Institute grant will enable Anbar to develop a suite of online virtual field trips that teach the story of Earth's evolution as an inhabited world. The virtual field trips will be based on nearly 4 billion years of Earth's geological record. These immersive, interactive virtual field trips will take students to locations that teach key insights into Earth's evolution, fundamental principles of geology and practices of scientific inquiry.
Anbar helped lead a multi-institutional team that developed a number of such virtual field trips for use in "Habitable Worlds" and elsewhere, supported by the NASA Astrobiology Institute and the National Science Foundation. Now, working with ASU education technologist and doctoral student Geoffrey Bruce, ASU professor and geoscience education specialist Steven Semken and partners at other institutions, Anbar will build virtual field trips (VFTs) covering the sweep of Earth's history. He and his team will take students to some of the most important places on Earth to explore how the planet came to be what it is today.
"The goal is to develop powerful and engaging new tools to teach about Earth's evolution," explains Anbar. "In the near term, we will create VFT-based lessons that can be incorporated into existing introductory geoscience courses. Right away, that can impact the roughly 2,000 majors and non-majors who take such courses each year at ASU, as well as thousands of students elsewhere. In the long run, we aim to create a fully online course like 'Habitable Worlds'-I'm calling it 'Evolving World' for now-that covers the content of one of the most important introductory geoscience courses, historical geology."
Anbar's plan could re-invigorate instruction in historical geology, which is taught in nearly every geoscience program. In addition to being fundamental to the field of geology, it provides vital context for the search for life beyond Earth and for the changes that humans are causing to the planet. However, historical geology is best taught through field experiences, which are logistically challenging at large universities. Even when they are possible, it is impossible to expose students to all the most scientifically important sites because they are scattered around the globe. While virtual field trips cannot rival physical field trips, they are a big advance over teaching this material only through lectures.
"Most science classes teach science as facts and answers," says Anbar. "With VFTs, as with Habitable Worlds, we are trying to teach that science is really a process-a process of exploration that helps us first organize our ignorance about questions to which we don't have answers, and then helps us narrow the uncertainties so that we can replace ignorance with understanding."
School of Earth and Space Exploration
July 1, 2014
A Magic Trick of Telomerase Revealed
Each time before a cell divides, DNA polymerases must make a copy of the genome. Similar to a typewriter, DNA polymerases type out the entire DNA sequence faithfully from the given parental script, without needing to understand the text.
Telomerase is a one-of-a-kind DNA polymerase with its own innate transcript for making DNA repeats at the ends of chromosomes within our cells. This special task of telomerase is intimately associated with human ageing, as the accelerated loss of DNA sequences from the ends of the genome results in genome instability, disease, infertility, and death.
Telomerase is distinguished from all known DNA polymerases by working as an intelligent typewriting enzyme. More specifically, this enzyme has the unparalleled talent to interpret the meaning of its script for synthesizing the intended DNA repeats. Researchers led by Prof. Julian J.-L. Chen at Arizona State University found that telomerase uses a previously unidentified signal embedded within the script itself to specify the precise phrase 'GGTTAG'. This unique ability is imperative for telomerase to magically type out many copies of the exact sequence GGTTAG through a repeated cycle. It is vitally important that telomerase types this exact phrase. An incomplete or incorrect phrase, by even a single letter, would not be understood by the cell and would damage it.
As Dr. Chen explains, "The message written by telomerase is read by additional proteins within the cell and thus must be accurately and precisely generated. Even the smallest change in the message would result in miscommunication with these critical proteins that protect our chromosomes, and would be extremely detrimental to the wellbeing of the cell." These findings, published this week in the journal Proceeding of the National Academy of Sciences, finally answer how human telomerase can reliably read its script so as to accurately and precisely type out the correct message to safeguard our genome.
This work was supported by the National Institutes of Health (NIH) (R01GM094450 to J.J.-L.C.) with the goal of fundamentally understanding telomerase for the future development of therapeutics against cancer, ageing, and disease.
"A self-regulating template in human telomerase", Brown, A.F., J.D. Podlevsky, X. Qi, Y. Chen, M. Xie, and J.J.-L. Chen, Proc. Natl. Acad. Sci. U.S.A. (2014) doi:10.1073/pnas.1402531111 (published online June 30th, 2014)
Source: Joshua Podlevsky, (480) 965-1928; email@example.com
Media contact: Jenny Green, (480) 965-1430; firstname.lastname@example.org
May 27, 2014
DNA nanotechnology places enzyme catalysis within an arm's length
Using molecules of DNA like an architectural scaffold, Arizona State University scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway that could prove important for future biomedical and energy applications.
The findings were published in the journal Nature Nanotechnology. Led by ASU Professor Hao Yan, the research team included ASU Biodesign Institute researchers Jinglin Fu, Yuhe Yang, Minghui Liu, Professor Yan Liu and Professor Neal Woodbury along with colleagues Professor Nils Walter and postdoctoral fellow Alexander Johnson-Buck at the University of Michigan.
Researchers in the field of DNA nanotechnology, taking advantage of the binding properties of the chemical building blocks of DNA, twist and self-assemble DNA into ever-more imaginative 2- and 3-dimensional structures for medical, electronic and energy applications.
In the latest breakthrough, the research team took up the challenge of mimicking enzymes outside the friendly confines of the cell. These enzymes speed up chemical reactions, used in our bodies for the digestion of food into sugars and energy during human metabolism, for example.
"We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level," Yan said, who holds the Milton Glick Chair in the ASU School of Molecular Sciences and directs the Center for Molecular Design and Biomimicry at the Biodesign Institute.
With enzymes, all moving parts must be tightly controlled and coordinated, otherwise the reaction will not work. The moving parts, which include molecules such as substrates and cofactors, all fit into a complex enzyme pocket just like a baseball into a glove. Once all the chemical parts have found their place in the pocket, the energetics that control the reaction become favorable, and swiftly make chemistry happen. Each enzyme releases its product, like a baton handed off in a relay race, to another enzyme to carry out the next step in a biochemical pathway in the human body.
For the new study, the researchers chose a pair of universal enzymes, glucose-6 phosphate dehydrogenase (G6pDH) and malate dehydrogenase (MDH), that are important for biosynthesis-making the amino acids, fats and nucleic acids essential for all life. For example, defects found in the pathway cause anemia in humans. "Dehydrogenase enzymes are particularly important since they supply most of the energy of a cell", said Walter. "Work with these enzymes could lead to future applications in green energy production such as fuel cells using biomaterials for fuel."
In the pathway, G6pDH uses the glucose sugar substrate and a cofactor called NAD to strip hydrogen atoms from glucose and transfer to the next enzyme, MDH, to go on and make malic acid and generate NADH in the process, which is used for as a key cofactor for biosynthesis.
Remaking this enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology.
To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes.
In the middle of the DNA scaffold, they affixed a single strand of DNA, with the NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes.
Once the system was made in a test tube by heating up and cooling the DNA, which leads to self-assembly, the enzyme parts were added in. They confirmed the structure using a high-powered microscope, called an AFM, which can see down to the nanoscale, 1,000 times smaller than the width of a human hair.
Like architects, the scientists first built a full-scale model so they could test and measure the spatial geometry and structures, including in their setup a tiny fluorescent dye attached to the swinging arm. If the reaction takes place, they can measure a red beacon signal that the dye gives off---but in this case, unlike a traffic signal, a red light means the reaction works.
Next, they tried the enzyme system and found that it worked just the same as a cellular enzyme cascade. They also measured the effect when varying the distance between the swinging arm and the enzymes. They found there was a sweet spot, at 7nm, where the arm angle was parallel to the enzyme pair.
With a single swinging arm in the test tube system working just like the cellular enzymes, they decided to add arms, testing the limits of the system with up to 4 added arms. They were able to show that as each arm was added, the G6pDH could keep up to make even more product, while the MDH had maxed out after only two swinging arms. "Lining enzymes up along a designed assembly line like Henry Ford did for auto parts is particularly satisfying for someone living near the motor city Detroit," said Walter.
The work also opens a bright future where biochemical pathways can be replicated outside the cell to develop biomedical applications such as detection methods for diagnostic platforms.
"An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature," said Yan.
The research is supported by a Multi-disciplinary University Research Initiative (MURI) grant from Army Research Office, with the goal of translating biochemical pathways into non-cellular environments.
Contact: Joe Caspermeyer
Arizona State University
|Julian Chen and his graduate student Dustin Rand in their ASU lab continuing research on the protein-RNA interaction in the vertebrate telomerase complex. Doctoral students Christopher Bley and Andrew Brown, also involved with the work, have graduated.
Photo by: Joshua Podlevsky
May 04, 2014
ASU, Chinese scientists unlock secrets of the fountain of youth
Arizona State University scientists, together with collaborators from the Chinese Academy of Sciences in Shanghai, have published a first of its kind atomic level look at the enzyme telomerase that may unlock the secrets to the fountain of youth in the journal Nature Structural and Molecular Biology.
Telomeres and the enzyme telomerase have been in the medical news a lot recently, due to their connection with aging and cancer. Telomeres are found at the ends of our chromosomes and are stretches of DNA which protect our genetic data, make it possible for cells to divide and hold some secrets as to how we age-and also how we get cancer.
An analogy can be drawn between telomeres at the end of chromosomes and the plastic tips on shoelaces: the telomeres keep chromosome ends from fraying and sticking to each other, which would destroy or scramble our genetic information.
Each time one of our cells divides, its telomeres get shorter. When they get too short, the cell can no longer divide, and it becomes inactive or dies. This shortening process is associated with aging, cancer and a higher risk of death. The initial telomere lengths may differ between individuals. Clearly, size matters.
"Telomerase is crucial for telomere maintenance and genome integrity," explains Julian Chen, professor of chemistry and biochemistry at ASU and one of the project's senior authors. "Mutations that disrupt telomerase function have been linked to numerous human diseases that arise from telomere shortening and genome instability."
Chen continues that, "Despite the strong medical applications, the mechanism for telomerase holoenzyme (the most important unit of the telomerase complex) assembly remains poorly understood. We are particularly excited about this research because it provides, for the first time, an atomic level description of the protein-RNA interaction in the vertebrate telomerase complex."
The other senior author on the project is professor Ming Lei, who has recently relocated from the University of Michigan to Shanghai, China, to lead a new National Center for Protein Science (affiliated with the Chinese Academy of Sciences).
At its core, telomerase is composed of two principle components: 1) a catalytic protein which synthesizes DNA from a template located within and 2) an intrinsic RNA component. Chen's laboratory has recently developed a means to highly purify an independently functional fragment of the telomerase protein. This functional telomerase protein fragment is aptly termed, Telomerase RNA Binding Domain (TRBD) for its RNA binding function. Additionally, Chen's researchers employed their purified protein to determine the specific region within TRBD responsible for binding a fragment of the telomerase RNA component, termed CR4/5.
The collaboration with Lei's group enabled the two laboratories to generate highly pure TRBD protein and successfully assemble this with the CR4/5 RNA for X-ray crystallography. X-ray crystallography involves bombarding the protein-RNA complex with high energy X-rays, which then scatter. By interpreting the scatter pattern, Lei's laboratory was able to determine the structure of the protein-RNA crystal, providing important insights into the binding of the RNA by the protein.
The mysteries of telomerase protein and RNA assembly are beginning to be exposed, with the exhaustive work of researchers within the telomerase field. The findings of professors Chen, Lei, and many others are improving our understanding of this fundamentally essential enzyme, slowly divulging its secrets which will be applied towards the development of therapeutics to enhance human health.
The School of Molecular Sciences in ASU's College of Liberal Arts and Sciences ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry), and in the top eight nationally for research publications in the journals Science and Nature. The department's strong record in interdisciplinary research is also evidenced by its 31st national ranking by the National Science Foundation in total and federally financed higher education research and development expenditures in chemistry.
This work was supported by grants from the US National Institutes of Health (RO1GM094450 to J.J.-L.C.), Ministry of Science and Technology of China (2013CB910400 to M.L.) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB08010201 to M.L.).
Jenny Green, email@example.com
School of Molecular Sciences
"Structural basis for protein-RNA recognition in telomerase", Jing Huang, Andrew F Brown, Jian Wu, Jing Xue, Christopher J Bley, Dustin P Rand, Lijie Wu, Rongguang Zhang, Julian J-L Chen & Ming Lei, Nature Structural & Molecular Biology (2014) doi:10.1038/nsmb.2819
|Basab Roy is a researcher at the Biodesign Institute's Center for BioEnergetics, under the direction of professor Sidney Hecht.
Photo by: Photo by Anais Bon
April 30, 2014
Cutting cancer to pieces: research sheds new light on anti-tumor agent
A variety of cancers are treated with the anti-tumor agent bleomycin, though its disease-fighting properties remain poorly understood.
In a new study, lead author Basab Roy, a researcher at Arizona State University's Biodesign Institute, describes bleomycin's ability to cut through double-stranded DNA in cancerous cells, like a pair of scissors. Such DNA cleavage often leads to cell death in particular types of cancer cells.
The paper is co-authored by professor Sidney Hecht, director of Biodesign's Center for BioEnergetics. The study presents, for the first time, alternative biochemical mechanisms for DNA cleavage by bleomycin. The new research will help inform efforts to fine-tune the drug, improving its cancer-killing properties while limiting toxicity to healthy cells.
Results of the study recently appeared in the Journal of the American Chemical Society.
Bleomycin is part of a family of structurally related antibiotics produced by the bacterium Streptomyces verticillus. Three potent versions of the drug, labeled A2 , A5 and B2, are the primary forms in clinical use against cancer.
Richard Harth, Richard.Harth@asu.edu
Bleomycin's cancer-fighting capacity was first observed in 1966 by Japanese researcher Hamao Umezawa. The drug gained FDA approval in 1973 and has been in use since then, particularly for the treatment of Hodgkin's lymphoma, squamous cell carcinomas and testicular cancer.
One of the attractive properties of bleomycin is the fact that it can be administered in fairly low doses, relative to many other cancer therapies. Previous research has shown that bleomycin can cause death in aberrant cells by migrating to the cell nucleus, binding with DNA and subsequently causing breaks in the DNA sequence. Following a binding event, a molecule of bleomycin can effectively slice through one or both strands of DNA.
Cleavage of DNA is believed to be the primary mechanism by which bleomycin kills cancer cells, particularly through double-strand cleavages, which are more challenging for the cellular machinery to repair. "There are several mechanisms for repairing both single-strand and double-strand breaks in DNA, but double-strand breaks are a more potent form of DNA lesion," Roy says.
The Center for BioEnergetics has been studying several forms of bleomycin, developing a sizeable library of variants, with the goal of engineering the best bleomycin analog. Roy is particularly interested in the subtle biochemistry of bleomycin, including the specificity of its binding regions along the DNA strand and the drug's detailed mechanisms of DNA cleavage.
For the new study, bleomycin A5 was used. Bleomycin A5 has similar DNA binding and cleaving properties as bleomycin A2 and B2. Previous research has revealed that bleomycin binds with highly specific regions of the DNA strand, typically G-C sites, where a guanosine base pairs with a cytidine. Further, the strength of this binding is closely associated with the degree of double-strand DNA cleavage.
From a pool of random DNA sequences, a library of 10 hairpin DNAs was selected, based on their strong binding affinity for bleomycin A5. Hairpin DNAs are looped structures, which form when a segment of a DNA strand base-pairs with another portion of the same strand. These hairpin DNAs were used to investigate double-strand cleavage by bleomycin.
Each of the 10 DNA samples underwent double-strand cleavage at more than one site. Further, all of the observed cleavage sites were found within or in close proximity to an 8 base pair variable region, which had been randomized to create the original library. Examination of the 10 DNA samples exposed to bleomycin revealed a total of 31 double-strand cleavage sites. Earlier research had described the form of double-strand DNA cleavage by bleomycin, which occurred at 14 of these sites; however, the remaining 17 cases of double-stranded cleavage occurred through a different mechanism, described for the first time in the present study.
As in earlier studies, iron (FeII) was used as a cofactor for bleomycin in the binding events. Two types of bleomycin binding and cleavage activity are detailed in the paper. In the first, bleomycin and its iron cofactor (Fe.BLM) bind with hairpin DNA at a primary site. Typically, this is a site with a particular sequence: 5'-G-Py-B-3'. (Here, 5' refers to one end of the DNA hairpin, G refers to the base guanosine, Py refers to a pyrimidinic base-either cytidine or thymidine-B refers to any nucleobase and 3' refers to the other DNA end.)
The result of this binding is the abstraction of a hydrogen atom at the primary site. Two results are possible following the primary binding event, one causing a single-strand break in the primary site, the other, failing to produce full cleavage of the strand, producing instead a site lacking either a purine or pyrimidine base. This is known as an AP site.
In the first case-where bleomycin achieves single strand cleavage-the bleomycin molecule can then become reactivated, once more abstracting a hydrogen atom from the opposing DNA strand. The opposite strand can again follow one of two pathways: a) full cleavage of the opposing strand, yielding a double strand cleavage, or b) formation of an AP site. The authors note that this AP site can lead to strand cleavage through the opposing DNA strand with the addition of a mild base like n-butylamine.
Results of the study emphasized the correlation between the strength of bleomycin binding to DNA and the frequency of double strand cleavage. Of the 10 sample hairpin DNAs, the two most tightly bound to bleomycin each showed 5 double strand cleavages, whereas the least tightly bound samples exhibited just two double strand cleavages.
This important study proposes, for the first time, a plausible mechanism for DNA cleavage by bleomycin that may lead to tumor cell killing, as well as identifying the most common sequences involved in DNA site binding and subsequent strand breakage.
Roy stresses that a great deal of work remains, to elucidate the biochemical causes of tight binding by bleomycin. Further, bleomycin's specificity for cancer cells remains enigmatic. New work in the Hecht lab, however, has identified the carbohydrate moiety of the molecule as being responsible for tumor cell targeting.
"Cancer is still a black hole," says Roy. "We're trying to make this particular molecule (bleomycin) better. There is still so much to learn."
In addition to his appointment at Biodesign, Basab Roy is a graduate student in the School of Molecular Sciences at ASU's College of Liberal Arts and Sciences.
The Biodesign Institut
April 10, 2014
Amino acid fingerprints revealed in new study
Some three billion base pairs make up the human genome-the floorplan of life. In 2003, the Human Genome Project announced the successful decryption of this code, a tour de force that continues to supply a stream of insights relevant to human health and disease.
Nevertheless, the primary actors in virtually all life processes are the proteins coded for by DNA sequences known as genes. For a broad spectrum of diseases, proteins can yield far more compelling revelations than may be gleaned from DNA alone if researchers can manage to unlock the amino acid sequences from which they are composed.
Now, Stuart Lindsay and his colleagues at Arizona State University's Biodesign Institute have taken a major step in this direction, demonstrating the accurate identification of amino acids by briefly pinning each in a narrow junction between a pair of flanking electrodes and measuring a characteristic chain of current spikes passing through successive amino acid molecules.
By using a machine-learning algorithm, Lindsay and his team were able to train a computer to recognize bursts of electrical activity representing the momentary binding of an amino acid within the junction. The noise signals were shown to act as reliable fingerprints, identifying amino acids, including subtly modified variants.
Proteins are already providing a wealth of information pertinent to diseases, including cancer, diabetes and neurological disorders like Alzheimer's, as well as furnishing key insights into another protein-mediated process: aging.
Richard Harth, Richard.Harth@asu.edu
The new work advances the prospect of clinical protein sequencing and the discovery of new biomarkers-early warning beacons signaling disease. Further, protein sequencing may radically transform patient treatment, enabling precise monitoring of disease response to therapeutics at the molecular level.
The group's research results are reported in the advanced online edition of the journal Nature Nanotech.
From genome to proteome
An enormous library of proteins, known as the proteome, occupies center stage in virtually all life processes. Proteins are vital for cellular growth, differentiation and repair; they catalyze chemical reactions and provide defense against disease, among myriad housekeeping functions.
One of the strangest surprises to emerge from the Human Genome Project is the fact that only about 1.5 percent of the genome codes for proteins. The rest of the DNA nucleotides form regulatory sequences, non-coding RNA genes, introns and noncoding DNA (once derisively labeled "junk DNA"). This leaves humans with a scant 20-25,000 genes, a sobering discovery given that the lowly roundworm has roughly the same number. As professor Lindsay notes, the news gets worse: "A lily plant has about an order of magnitude more genes than we do," he says.
The mystery of complex organisms like humans bearing an appallingly low gene number has to do with the fact that proteins generated from the DNA blueprint can be modified in a number of ways. In fact, scientists have already identified over 100,000 human proteins, and researchers like Lindsay believe this may be only the tip of the iceberg.
Just as sentences can have their meanings altered through changes in word order or punctuation, proteins generated from gene templates can change function (or sometimes be rendered inoperable), often with serious consequences for human health. Two key processes that modify proteins are known as alternative splicing and post-translational modification. They are the drivers of the extraordinary protein variation observed.
Alternative splicing occurs when coding regions of RNA (known as exons) are spliced together, and non-coding regions (known as introns) are snipped out prior to translation into proteins. This process does not always occur neatly, with occasional overlaps of exons or introns being introduced, producing alternatively spliced proteins, whose function may be altered.
Post-translational modifications are markers added after proteins have been made. There are many forms of post-translational modification, including methylation and phosphorylation. Some altered proteins perform vital functions, while others may be aberrant and associated with disease (or disease propensity). A number of cancers are associated with such protein errors, which are already used as diagnostic markers. Proper identification of such proteins, however, remains a grand challenge in biomedicine.
The technique described in the current research was earlier applied in the Lindsay lab for the successful sequencing of DNA bases. This method, known as recognition tunneling, involves threading a peptide through a tiny eyelet known as a nanopore. A pair of metal electrodes, separated by a gap of roughly two nanometers, sits on either side of the nanopore as successive units of a peptide are threaded through the tiny aperture, with each unit completing an electrical circuit and emitting a burst of current spikes.
The research group demonstrated that close analyses of these current spikes could enable researchers to determine which of the four nucleotide bases-adenine, thymine, cytosine or guanine-was poised between the electrodes in the nanopore.
"About two years ago in one of our lab meetings, it was suggested that maybe the same technology would work for amino acids," Lindsay says. Thus began efforts to tackle the substantially greater challenge of using recognition tunneling to identify all 20 amino acids found in proteins, as opposed to just four bases comprising DNA.
Single-molecule sequencing of proteins is of enormous value, offering the potential to detect diminishingly small quantities of proteins that may have been tweaked by alternative splicing or post-translational modification. Often, these are the very proteins of interest from the standpoint of recognizing disease states, though current technologies are inadequate to detect them.
As Lindsay notes, there is no equivalent in the protein world to polymerase chain reaction (PCR) technology, which allows minute quantities of DNA in a sample to be rapidly amplified. "We probably don't even know about most of the proteins that would be important in diagnostics. It's just a black hole to us because the concentrations are too low for current analytical techniques," he says, adding that the ability of recognition tunneling to pinpoint abnormalities on a single molecule basis "could be a complete game changer in proteomics."
The new paper describes a series of experiments in which pure samples of individual amino acids, individual molecules in mixed solution and short peptide chains were successfully identified through recognition tunneling. The work sets the stage for a method to sequence individual protein molecules rapidly and cheaply (see accompanying animation).
A machine-learning algorithm known as Support Vector Machine was used to train a computer to analyze the burst signals produced when amino acids formed bonds in the tunnel junction and emitted a lively noise signal as the poised electrodes passed, tunneling current through each molecule. (The machine-learning algorithm is the same one used by the IBM computer "Watson" to defeat a human opponent in Jeopardy.)
Lindsay says that around 50 distinct signal burst characteristics were used in the amino acid identifications but that most of the discriminatory power is achieved with 10 or fewer signal traits.
Remarkably, recognition tunneling not only pinpointed amino acids with high reliability from single complex burst signals, but managed to distinguish a post-translationally modified protein (sarcosine) from its unmodified precursor (glycine), and also to discriminate between mirror-image molecules known as enantiomers, and so-called isobaric molecules, which differ in peptide sequence but exhibit identical masses.
Pathway to the $1,000 dollar proteome?
Lindsay indicates that the new studies, which rely on innovative strategies for handling single molecules coupled with startling advances in computing power, open up horizons that were inconceivable only a short time ago. It is becoming clear that the tools that made the $1,000 genome feasible are equally applicable to an eventual $1,000 proteome. Indeed, such a landmark may not be far off. "Why not?" Lindsay asks. "People think it's crazy, but the technical tools are there, and what will work for DNA sequencing will work for protein sequencing."
While the tunneling measurements have until now been made using a complex laboratory instrument known as a scanning tunneling microscope (STM), Lindsay and his colleagues are currently working on a solid state device capable of fast, cost-effective and clinically applicable recognition tunneling of amino acids and other analytes. Eventual application of such solid-state devices in massively parallel systems should make clinical proteomics a practical reality.
Stuart Lindsay is the director of Biodesign's Center for Single-Molecule Biophysics, the Edward and Nadine Carson Presidential Chair in Physics at ASU and Regents Professor in the College of Liberal Arts and Sciences, Chemistry and Biochemistry.
The current research received funding from the National Institute of Health's National Human Genome Research Institute (NHGRI).
The Biodesign Institute
April 4, 2014
|Ryan Muller, biochemistry and molecular/cellular biology major at ASU.
Three outstanding ASU juniors, including biochemistry major, win Goldwater scholarships
Three outstanding Arizona State University juniors who already are doing sophisticated research have won Goldwater Scholarships, the nation's premier awards for undergraduates studying science, math and engineering.
Working in the laboratories of ASU senior faculty and scientists, the students carry out research ranging from developing biosensors for early detection of infectious diseases to conducting microelectronics research at ASU's Flexible Display Center.
Recipients are Ryan Muller of Phoenix, majoring in biochemistry and molecular/cellular biology; Brett Larsen of Chandler, majoring in electrical engineering and physics; and Jakob Hansen of Mesa, a mathematics and economics major. Each of the four will receive $7,500 a year for up to two years.
All are in the College of Liberal Arts and Sciences, while Larsen is also in the Fulton Schools of Engineering. All three are enrolled in Barrett, the Honors College. A fourth student who received honorable mention is Samuel Blitz, a physics major from Scottsdale.
ASU students have won 55 Goldwater Scholarships in the last 21 years, placing ASU among the leading public universities.
Muller is a resourceful and motivated student who began doing research at ASU while still a student at North High School, and again the summer before his freshman year. Xiao Wang, assistant professor in the School of Biological and Health Systems Engineering, remembers that even though Muller was initially the youngest member of the iGEM synthetic biology research team, others quickly began to rely on him.
"His ideas were fresh, innovative and motivating to the team," says Wang. "In fact, the first day he volunteered in my lab, without any prior experience, he implemented a strategy to effectively screen for bacterial colonies that contained the correct transformed plasmid. The team began to rely on his resourcefulness."
In subsequent years, Muller continued working on the team and was a key player in helping them develop a portable, low-cost biosensor system to detect pathogens in water supplies. They won a gold medal and a spot in the international championship event for one of the world's premiere student engineering and science competitions.
Interested in expanding their work, Muller and others assembled a team of undergraduate researchers to seek additional funding. Last year, they were grand prize winners at the ASU Innovation Challenge and at the ASU Edson Student Entrepreneur Initiative. Their fledgling company, Hydrogene Biotechnologies, may help cut down on water-borne diseases that can kill, such as acute childhood diarrhea.
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Hansen, a graduate of Red Mountain High School, is a talented mathematician who has been a delight to his professors as someone who enjoys the formal beauty of mathematics, yet is committed to doing research into real problems that affect humans.
"Jakob is exceptionally talented at mathematics, and is one of relatively few undergraduates that I have taught at ASU who was equally enthusiastic about pure and applied mathematics," says Jay Taylor, assistant professor in the School of Mathematics and Statistical Sciences. "He was always very keen to discuss the theory underpinning the techniques that I presented in class.
"For his project, he wrote a computer program to simulate a malaria outbreak in a small population and used this to investigate the conditions under which malaria will persist in small populations subject to seasonal variation in transmission intensity."
Hansen participated in ASU's Computational Science Training for Undergraduates last summer with Rosemary Renaut, professor of mathematics, who praised his mathematical sophistication to the Goldwater committee. He is continuing his research with Renault into more abstract problems.
Larsen, a graduate of Tri-City Christian Academy, received funding early in his career from the Fulton Undergraduate Research Initiative. Over the past two years, he has conducted research at ASU's Flexible Display Center, developing ultra low-power circuits and applying advanced signal processing techniques to personnel detection along borders and in hostile territory.
Larsen says his interest in science was sparked by a Boy Scout leader, an electrical engineer who talked to him about subjects that enthralled him: objects traveling at the speed of light, the astonishing power of fusion and fission reactions, and theoretical designs for time machines and light sabers. Larsen was inspired to excel in science so he could push the boundaries of technology.
Called "a brilliant young man" by Antonia Papandreou-Suppappola, professor of electrical engineering, Larsen shares his love of science by mentoring a group of engineering freshmen and leading a science club for young children at the Child Crisis Center. In the future, he hopes to focus his work on developing mathematical models for defense applications.
"ASU's success in the Goldwater competition is in large part due to the excellent opportunities our students have had to do advanced lab research with talented and committed faculty," says Janet Burke, associate dean for national scholarship advisement in Barrett, the Honors College.
"It goes without saying that the drive and brilliance of the students themselves are both important. I have a top-notch Goldwater committee who do a superb job of selecting the students whose applications will bubble to the top of the pile."
April 1, 2014
ASU leads new national research network to study impacts of nanomaterials
Arizona State University researchers will lead a multi-university project to aid industry in understanding and predicting the potential health and environmental risks from nanomaterials.
Nanoparticles, which are approximately 1 to 100 nanometers in size, are used in an increasing number of consumer products to provide texture, resiliency and in some cases antibacterial protection.
The U.S. Environmental Protection Agency (EPA) has awarded a grant of $5 million over the next four years to support the LCnano Network as part of the Life Cycle of Nanomaterials project, which will focus on helping to ensure the safety of nanomaterials throughout their life cycles-from the manufacture to the use and disposal of the products that contain these engineered materials.
Paul Westerhoff is the LCnano Network director. Westerhoff is the associate dean of research for ASU's Ira A. Fulton Schools of Engineering and a professor in the School of Sustainable Engineering and the Built Environment.
The project will team engineers, chemists, toxicologists and social scientists from ASU, Johns Hopkins, Duke, Carnegie Mellon, Purdue, Yale, Oregon's state universities, the Colorado School of Mines and the University of Illinois-Chicago.
Engineered nanomaterials of silver, titanium, silica and carbon are among the most commonly used. They are dispersed in common liquids and food products, embedded in the polymers from which many products are made, and attached to textiles, including clothing.
Nanomaterials provide clear benefits for many products, Westerhoff says, but there remains "a big knowledge gap" about how, or if, nanomaterials are released from consumer products into the environment as they move through their life cycles, eventually ending up in soils and water systems.
"We hope to help industry make sure that the kinds of products that engineered nanomaterials enable them to create are safe for the environment," Westerhoff says.
"We will develop molecular-level fundamental theories to ensure the manufacturing processes for these products is safer," he explains, "and provide databases of measurements of the properties and behavior of nanomaterials before, during and after their use in consumer products."
Among the bigger questions the LCnano Network will investigate are whether nanomaterials can become toxic through exposure to other materials or the biological environs they come in contact with over the course of their life cycles, Westerhoff says.
The researchers will collaborate with industry-both large and small companies-and government laboratories to find ways of reducing such uncertainties.
Among the objectives is to provide a framework for product design and manufacturing that preserves the commercial value of the products using nanomaterials, but minimizes potentially adverse environmental and health hazards.
In pursuing that goal, the network team will also be developing technologies to better detect and predict potential nanomaterial impacts.
Beyond that, the LCnano Network also plans to increase awareness about efforts to protect public safety as engineered nanomaterials in products become more prevalent.
The grant will enable the project team to develop educational programs, including a museum exhibit about nanomaterials based on the LCnano Network project. The exhibit will be deployed through a partnership with the Arizona Science Center and researchers who have worked with the Nanoscale Informal Science Education Network.
The team also plans to make information about its research progress available on the nanotechnology industry website Nanohub.org.
"We hope to use Nanohub both as an internal virtual networking tool for the research team and as a portal to post the outcomes and products of our research for public access," Westerhoff says.
The grant will also support the participation of graduate students in the Science Outside the Lab program, which educates students on how science and engineering research can help shape public policy.
Other ASU faculty members involved in the LCnano Network project are:
Pierre Herckes, associate professor, School of Molecular Sciences, College of Liberal Arts and Sciences
Kiril Hristovski, assistant professor, Department of Engineering, College of Technology and Innovation
Thomas Seager, associate professor, School of Sustainable Engineering and the Built Environment
David Guston, professor and director, Consortium for Science, Policy and Outcomes
Ira Bennett, assistant research professor, Consortium for Science, Policy and Outcomes
Jameson Wetmore, associate professor, Consortium for Science, Policy and Outcomes, and School of Human Evolution and Social Change
Media Contact: Joe Kullman, email@example.com (480) 965-8122 Ira A. Fulton Schools of Engineering
March 17, 2014
ASU LightWorks spearheads partnership with AORA
Solar-generated electricity, which can suffer from intermittency issues and related impacts on the grid, is about to blossom at Arizona State University. Work will now begin on the development of a hybrid concentrated solar system, following a contract signing with ASU and AORA to provide research expertise in order to enhance the efficiency of this unique technology.
AORA Solar NA has agreed to install the first ever Solar Tulip hybrid generating facility in the United States on university land, and ASU faculty, research staff and students will work hand in hand with AORA to enhance the system.
This project includes the installation of a hybrid concentrated solar power plant that employs a Solar Tulip to concentrate the sun's energy, turning it into electricity. The system produces power 24/7, moving seamlessly from solar to natural gas or biogas, and is also promising because it uses little to no water while producing a high quality thermal output in addition to power.
AORA Solar NA, a U.S. company, will work with a multidisciplinary ASU team to research options to increase efficiency, improve reliability, utilize the exhaust heat and decrease the cost of this Israeli-developed technology. AORA will construct the demonstration power plant, which includes a tower (approximately 100 feet high) appropriately called the Solar Tulip, on undeveloped land near the Karsten Golf Course in Tempe.
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The technology includes a collection of mirrors to concentrate the sun's rays to heat compressed air to more than 1800 degrees Fahrenheit and drive a gas turbine. The rated output of the system is 100 kilowatts of electricity and an additional 170 kilowatts of thermal energy, about enough energy to power between 60-80 homes.
At night, or when overcast, the Tulip can use a wide range of fuels to heat the air, and is thereby able to produce power and heat around the clock. The system is modular in design, allowing for multiple Tulips to work together, enabling the technology to match growing electric demand requirements. The relatively small footprint makes this system a potentially perfect complement to housing developments or industrial parks, and offers an option to enhance grid stability in the presence of transient renewable generation.
"ASU is a natural partner for us, not only because of its sunny location, but because of the university's dedication to innovation and sustainability," said Zev Rosenzweig, CEO of AORA Solar. "We are excited to make our debut here in the United States with this innovative technology, where we will continue to grow and develop the Tulip into a system that cities and industries around the world use to generate continuous energy with renewable resources.
"ASU's breadth of research capability will undoubtedly allow us to increase output and reduce overall costs, which will bring us to commercial viability. Our confidence in this project is enhanced with the participation of project director, Ellen Stechel, who has spearheaded the concept from the beginning, along with her colleagues Gary Dirks, William Brandt and the ASU LightWorks team."
AORA Solar is currently operating two additional research facilities, one located in a solar research park in Almeria, Spain, and the original unit in Israel. These systems can be controlled remotely via computer, a unique capability that provides innovative options for possibilities in the U.S. and, indeed, around the world, including developing countries.
The ASU/AORA collaborative relationship will not only bring ASU closer to its goal of becoming carbon neutral by 2025, but it will also benefit students and researchers across multiple fields of study.
"This is another instance in which ASU has brought in cutting-edge technology that its students can learn from and help perfect," said Sethuraman "Panch" Panchanathan, senior vice president of Office of Knowledge Enterprise Development at ASU. "With this collaboration, the university has established a commitment to integrate students, faculty and staff into research on the Solar Tulip design to bring 24-hour solar/renewable technology to commercialization."
"The AORA/ASU collaboration provides a multitude of possibilities looking forward," said Gary Dirks, director of ASU LightWorks. "It is a perfect example of industry and academia coming together and leveraging their unique strengths to create collaborative projects that propel new and viable technology into our energy future. The Solar Tulip has enormous potential, both at ASU and beyond."
AORA Solar has contracted with GreenFuel Technologies, a Phoenix-based General Contractor specializing in environmental energy projects, to construct the research plant at the ASU campus. The groundbreaking is expected to occur in April, with the anticipated operation date to be sometime in the late September/early October time frame. AORA Solar and ASU look forward to welcoming university peers, along with the public, to a ribbon-cutting event at the Tulip's completion.
"We are pleased to host the Solar Tulip at the ASU Tempe campus," said John Riley, sustainability operations officer at ASU. "It is a visually iconic piece of technology, helping to illustrate the way ASU is a destination place for state-of-the-art research and facilities."
This collaboration was advanced by Arizona State University LightWorks, a research initiative that unites resources and researchers across ASU to confront global energy challenges. The LightWorks team provided the vision of required research, identified the multiple research windows in which AORA will participate and is intimately involved in moving the project from concept to fruition. With a proven track record of swiftly and strategically partnering with a diverse set of institutions, LightWorks continues to help overcome challenges in the fields of solar power, sustainable fuels and energy policy. To learn more about ASU LightWorks, visit asulightworks.com.
Office of Knowledge Enterprise Development
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March 11, 2014
ASU chemistry grad appointed as WPI's first female president
Laurie Leshin has helped send robots to Mars, overseen NASA's largest science center, commanded research on human space exploration, and even has a piece of the solar system named after her.
The 48-year-old geochemist and space scientist's next mission: leading Worcester Polytechnic Institute as the first woman president in its 149-year history.
"My favorite thing in the world is learning new things and meeting new people. It's like candy to me," said Leshin, who is currently a dean at Rensselaer Polytechnic Institute in New York. Leshin said she hopes to "turn up the volume" on the "many things WPI already has going for it."
A self-described "space nerd," Leshin shares a birthday with astronaut Neil Armstrong and is a member of the team that launched the Mars Curiosity rover mission.
Once asked by an interviewer about her propensity for referring to Curiosity as a "she," Leshin said it was "because she's smart and good-looking."
Though WPI is small in size, its stature has been growing recently, thanks in part to its research in the booming robotics field.
Its ties to NASA include hosting a major robotics contest for student teams in conjunction with the space agency.
And in December, WPI researchers finished seventh in a prestigious robot throwdown run by the Pentagon's Defense Advanced Research Projects Agency that featured teams running a 330-pound humanoid robot through emergency rescue situations.
The WPI team finished ahead of teams from NASA's own Johnson Space Center and the Advanced Technology Laboratories of space giant Lockheed Martin.
Leshin is scheduled to officially take over as WPI's 16th president in July, in time for the start of the school's next academic year.
School officials said she was the "unanimous first choice" of university trustees, who spent six months sifting among 200 candidates for the position. She joined Rensselaer in 2011.
She replaces Dennis D. Berkey who stepped down in May after leading WPI for nine years.
Her prodigious scientific pedigree includes several senior-level administrative positions at NASA, including helping to oversee the agency's human spaceflight activities.
She also helped run the Goddard Space Flight Center in Maryland, a massive facility that conducts research on space and builds spacecraft, instruments, and new technology.
The Goddard center is named after Robert Hutchings Goddard, a WPI alumnus who built and launched the world's first liquid-fueled rocket from a farm in Auburn, Mass., in 1926.
Among Leshin's many awards and honors is something few others are likely to duplicate: She has a patch of outer space with her name on it. "4922 Leshin" is a several-mile long strip of matter in the so-called main belt of asteroids that are roughly located between the planets Mars and Jupiter.
The International Astronomical Union named the asteroid in recognition of her contributions to planetary science.
Leshin said she first discovered her love for space at age 10 when she read a copy of Time magazine on her mother's kitchen table in her hometown of Tempe, Ariz. The magazine showed pictures of the surface of Mars taken by NASA spacecraft in the Viking program.
"It looked a lot like the desert landscape around where I grew up," she recalled.
Leshin earned a bachelor's degree in chemistry from Arizona State University in 1987 before later earning a master's and a doctorate in geochemistry from California Institute of Technology.
She is married to astrophysicist and former NASA official Jon Morse. And her scientific specialty sounds other-worldy -cosmochemistry; according to her biography, while at NASA, she was "primarily interested in deciphering the record of water on objects in our solar system."
"Laurie Leshin is impressive by any measure," said the chairman of WPI's trustees, Warner Fletcher. "She is an academic who understands the role of -and the potential for -academia in the larger world. She is well positioned to take WPI to an even higher level of excellence and prominence."
WPI is small in comparison to engineering powerhouses such as the Massachusetts Institute of Technology and Stanford University -about 4,000 undergraduates and some 1,900 full- and part-time graduate students.
But it has been rising in prominence.
In 2009, NASA awarded a WPI team $500,000 for its winning entry in a contest to build a robot that could move lunar soil.
WPI dominated the contest by building "Moonraker 2.0," a robot that moved about 960 pounds of dirt within 30 minutes.
And its showing in the DARPA robot challenge in December was good enough to put WPI in the finals of the competition, battling it out with MIT and a prestigious team of Japanese scientists for a $2 million prize.
Leshin cited the "high quality" WPI faculty and students and the school's "distinct interdisciplinary project-based approach to learning."
She said the project-based curriculum at WPI reminds her of how NASA operates
An avid Twitter user, Leshin uses social media to communicate with students, faculty, and others in her field. On Tuesday, she received dozens of messages on Twitter offering congratulations.
"I'm up 1,000 followers today," Leshin said, laughing. "It's amazing."
Michael B. Farrell of the Globe staff contributed to this report. Matt Rocheleau can be reached at firstname.lastname@example.org. For more coverage of area colleges and universities, visit boston.com/yourcampus.
February 18, 2014
ASU hosts You Be The Chemist Challenge
Middle school students from across Maricopa County showed off their knowledge of chemistry concepts by competing for a spot in the Chemical Educational Foundation's 10th annual National You Be The Chemist Challenge on Tuesday on the Tempe campus. Chemistry professor Jennifer Green hosted the event.
BIYA Global and Brenntag Pacific Inc. also sponsored the competition.
CEF is a nationally recognized nonprofit organization meant to boost education in science.
The event is an academic challenge that uses the structure of a competition to encourage middle school students to explore important chemistry concepts, scientific discoveries and laboratory concepts. CEF outreach assistant Elena Lien said ASU would host the local competition and the winner would go on to compete in the state competition and eventually the national competition.
The competition hosted by ASU was the Maricopa County Challenge.
"Around 25,000 middle school students compete," she said. "This isn't a science fair; it's structured a lot like the National Spelling Bee."
Lien said CEF organizes and hosts the National Challenge in Philadelphia. Each state winner will receive an all-expenses-paid trip to the competition in June.
"This year is extra special because the competition is celebrating its 10th anniversary," she said.
The Challenge program relies on partnerships with community members who seek to support student engagement with science.
Participation in the challenge is open to middle school students across the U.S. CEF produces the study materials and questions for each level of the competition. Students have the chance to study material on the CEF website.
The questions align with Next Generation Science Standards. They include basic science concepts that appear in many state assessments.
A team of chemical industry members, professors and curriculum specialists develop the questions.
Challenge questions and materials also integrate language arts and history concepts, which present chemistry questions in an educational and entertaining format.
CEF Executive Director John Rice said the challenge enlivens the learning engagement for students.
"CEF is continually impressed by Challenge participants' grasp of scientific concepts and dedication to expanding their science knowledge," he said. "As CEF celebrates the 10th anniversary of the Challenge, we are eager to see how past and future participants will contribute their talents to the scientific community."
The top four participants in the local challenge received gift cards, trophies and other prizes.
The competition consisted of six rounds plus a practice round. There were four introductory rounds, a semi-final round and a championship round.
Participants were given clickers and instructed to answer chemistry questions formatted in a multiple choice setting. They were later given dry-erase boards to write their answers on in the final rounds.
This year, 15 students participated in the local challenge. Various numbers of students were eliminated after each introductory round, leaving four students to compete in the semi-final round and eventually two students in the championship round.
Center for Educational Excellence member Cheryl Hogan said those who tied were to compete in a lightning round.
"I think it's really great to see these children have such great interest in chemistry and sciences," she said.
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|An artificial photosynthetic reaction center containing a bioinspired electron relay (yellow) mimics some aspects of photosynthesis.
February 18, 2014
Artificial leaf jumps developmental hurdle
In a recent early online edition of Nature Chemistry, ASU scientists, along with colleagues at Argonne National Laboratory, have reported advances toward perfecting a functional artificial leaf.
Designing an artificial leaf that uses solar energy to convert water cheaply and efficiently into hydrogen and oxygen is one of the goals of BISfuel-the Energy Frontier Research Center, funded by the Department of Energy, in the School of Molecular Sciences at Arizona State University.
Hydrogen is an important fuel in itself and serves as an indispensible reagent for the production of light hydrocarbon fuels from heavy petroleum feed stocks. Society requires a renewable source of fuel that is widely distributed, abundant, inexpensive and environmentally clean.
Society needs cheap hydrogen.
"Initially, our artificial leaf did not work very well, and our diagnostic studies on why indicated that a step where a fast chemical reaction had to interact with a slow chemical reaction was not efficient," said ASU chemistry professor Thomas Moore. "The fast one is the step where light energy is converted to chemical energy, and the slow one is the step where the chemical energy is used to convert water into its elements viz. hydrogen and oxygen."
The researchers took a closer look at how nature had overcome a related problem in the part of the photosynthetic process where water is oxidized to yield oxygen.
"We looked in detail and found that nature had used an intermediate step," said Moore. "This intermediate step involved a relay for electrons in which one half of the relay interacted with the fast step in an optimal way to satisfy it, and the other half of the relay then had time to do the slow step of water oxidation in an efficient way."
They then designed an artificial relay based on the natural one and were rewarded with a major improvement.
Seeking to understand what they had achieved, the team then looked in detail at the atomic level to figure out how this might work. They used X-ray crystallography and optical and magnetic resonance spectroscopy techniques to determine the local electromagnetic environment of the electrons and protons participating in the relay, and with the help of theory (proton coupled electron transfer mechanism), identified a unique structural feature of the relay. This was an unusually short bond between a hydrogen atom and a nitrogen atom that facilitates the correct working of the relay.
They also found subtle magnetic features of the electronic structure of the artificial relay that mirrored those found in the natural system.
Not only has the artificial system been improved, but the team understands better how the natural system works. This will be important as scientists develop the artificial leaf approach to sustainably harnessing the solar energy needed to provide the food, fuel and fiber that human needs are increasingly demanding.
ASU chemistry professors involved in this specific project include Thomas Moore, Devens Gust, Ana Moore and Vladimiro Mujica. The department is a unit of the College of Liberal Arts and Sciences. Key collaborators in this work are Oleg Poluektov and Tijana Rajh from Argonne National Laboratory.
This work would not have been possible without the participation of many scientists driven by a common goal and coordinated by a program such as the Energy Frontier Research Center to bring the right combination of high-level skills to the research table.
The Department of Chemisry and Biocehmistry is an academic unit in ASU's College of Liberal Arts and Sciences.
Jenny Green, firstname.lastname@example.org
School of Molecular Sciences
January 29, 2014
X-ray lasers get to the heart of the matter: Fromme & Spence research highlighted in current issue of Nature
In the foothills above Palo Alto, California, physicists have set up an extreme obstacle course for some of the world's fastest electrons. First the particles are accelerated through a 3-kilometre vacuum pipe to almost the speed of light. Then they slam through a gauntlet of magnets that forces them into a violent zigzag. They respond with a blast of X-rays so fierce it could punch through steel.
But the scientists at the SLAC National Accelerator Laboratory have no interest in weaponry. Their machine, one of the world's most powerful X-ray free-electron lasers (XFELs), is a tool for studying challenging forms of matter, whether compressed to the kind of pressures and temperatures found deep inside a star, or folded into the complex tangle of a protein molecule.
Richard P. Van Duyne, Charles E. and Emma H. Morrison Professor of Chemistry, Professor of Biomedical Engineering, and Professor in the Applied Physics program at Northwestern University, to give Spring Eyring Lectures
"Molecular Plasmonics: Nanoscale Spectroscopy and Sensing"
7:30 PM, PSH-151
"New Tools for the Study of Single Molecule Chemistry at the Atomic Length Scale and Femtosecond Time Scale"
3:40 PM, PSH-151
Professor Van Duyne discovered surface-enhanced Raman spectroscopy (SERS), invented nanosphere lithography (NSL), and developed ultrasensitive nanosensors based on localized surface plasmon resonance (LSPR) spectroscopy.
His research interests include all forms of surface-enhanced spectroscopy, plasmonics, nanoscale biosensors, atomic layer deposition (ALD), atomic force microscopy (AFM), scanning tunneling microscopy (STM), ultra-high vacuum (UHV) STM, UHV-tip-enhanced Raman spectroscopy (UHV-TERS), and surface-enhanced femtosecond stimulated Raman spectroscopy (SE-FSRS).
Professor Van Duyne has been recognized for his accomplishments with several recent honors including the American Chemical Society's E. Bright Wilson Award in Spectroscopy, (2014), the Charles Mann Award in Applied Raman Spectroscopy, from the Society of Applied Spectroscopy (2014), and the Sir George Stokes Award, Royal Society of Chemistry (2013). He was made an Honorary Member of the Society of Applied Spectroscopy last year. In 2011 Van Duyne made the Thomson Reuters list of top 100 chemists over the period 2000-2010 as ranked by the impact of their published research.
Other awards include the Charles N. Reilley Award, Society for Electroanalytical Chemistry (2011); Election to the US National Academy of Sciences (2010); Award in Analytical Chemistry, American Chemical Society (2010); Bomem-Michelson Award, Coblentz Society (2010); Ellis R. Lippincott Award, Optical Society of America (2008); Professeur invite classe exceptionnelle- University Pierre et Marie Curie, Paris (2008); Special Creativity Award, National Science Foundation (2007); L'Oreal Art and Science of Color Prize (2006); Nobel Laureate Signature Award for Graduate Education, American Chemical Society (2005); Election to the American Academy of Arts and Sciences (2004); and The Earle K. Plyler Prize for Molecular Spectroscopy, American Physical Society (2004).
Van Duyne received his B.Sc. degree from Rensselaer Polytechnic Institute (1967) and a PhD. degree in analytical chemistry from the University of North Carolina (1971).
More information on EYRING LECTURERS
|ASU researchers Dingjie Wang and Garrett Nelson insert a lipid cubic phase injector containing tiny crystals of G protein-coupled receptors into the sample chamber during an experiment at the Linac Coherent Light Source's Coherent X-ray Imaging instrument station.
Photo by: Fabricio Sousa/SLAC
January 6, 2014
ASU researchers report major advance in human proteins
A group of researchers from Arizona State University is part of a larger team reporting a major advance in the study of human proteins that could open up new avenues for more effective drugs of the future. The work is being reported in this week's Science magazine.
In the paper, "Serial femtosecond crystallography of G-protein-coupled receptors," the team reports it has been successful in imaging, at room temperature, the structure of G protein-coupled receptors (GPCR) with the use of an X-ray free-electron laser.
GPCRs are highly diverse membrane proteins that mediate cellular communication. Because of their involvement in key physiological and sensory processes in humans, they are thought to be prominent drug targets.
The method described in the paper was applied for the first time to this important class of proteins, for which the 2012 Nobel Prize was awarded to Brian Kobilka and Robert Lefkowitz, said John Spence, an ASU Regents' Professor of physics. Spence is also the director of science at National Science Foundation's BioXFEL Science and Technology Center, and a team member on the Science paper.
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"These GPCRs are the targets of a majority of drug molecules," Spence said, but they are notoriously difficult to work with. This is the first time structural observations of the GPCRs have been made at room temperature, allowing researchers to overcome several disadvantages of previous imaging methods of the proteins.
"Normally, protein crystallography is performed on frozen samples, to reduce the effects of radiation damage," Spence said, "but this new work was based on an entirely new approach to protein crystallography, called SFX (Serial Femtosecond Crystallography), developed jointly by ASU, the Deutsches Elektronen-Synchrotron (DESY) and the SLAC National Accelerator Laboratory.
"This method uses brief pulses of X-rays instead of freezing the sample to avoid damage, and so it reveals the structure which actually occurs in a cell at room temperature, not the frozen structure," Spence added. "The 50 femtosecond pulses (120 per second) 'outrun' radiation damage, giving a clear picture of the structure before it is vaporized by the beam."
The femtosecond crystallography technique could enable researchers to view molecular dynamics at a time-scale never observed before. Spence said the method basically operates by collecting the scattering for the image so quickly that images are obtained before the sample is destroyed by the X-ray beam.
By "outrunning" radiation-damage processes in this way, the researchers can record the time-evolution of molecular processes at room temperature, he said.
Spence said ASU played a crucial role in the project described in Science, through the invention by ASU physics professor Uwe Weierstall of an entirely new device for sample delivery suited to this class of proteins.
The lipic cubic phase (LCP) injector that Weierstall developed replaces the continuous stream of liquid (which sends a continuously refreshed stream of proteins across the pulsed X-ray beam) with a slowly moving viscous stream of "lipid cubic phase solution," which has the consistency of automobile grease.
"We call it our 'toothpaste jet,'" Spence said.
He added that the LCP solves three problems associated with previous SFX work, which made this new work possible:
- The viscosity slows the flow rate so the crystals emerge at about the same rate as the X-ray pulses come along, hence no protein is wasted. This is important for the study of human protein, which is more costly than diamond on a per gram basis.
- The "hit rate" is very high. Nearly all X-ray pulses hit protein particles.
- Most important, LCP is itself a growth medium for protein nanocrystals.
"A big problem with the SFX work we have been doing over the past four years is that people did not know how to make the required nanocrystals," Spence said. "Now it seems many can be grown in the LCP delivery medium itself."
The international team reporting the advance in Science includes researchers from the Scripps Research Institute, La Jolla, Calif.; the Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany; the Department of Physics and the School of Molecular Sciences at ASU, Tempe, Ariz.; SLAC National Accelerator Laboratory, Menlo Park, Calif.; Trinity College, Dublin, Ireland; Uppsala University, Sweden; University of Hamburg, Germany; and Center for Ultrafast Imaging, Hamburg, Germany.
The collaboration between the team at ASU and the research groups at the Scripps Research Institute led by Professor Vadim Cherzov was initiated by Petra Fromme at ASU as a collaboration between two of the membrane protein centers of the Protein Structure Initiative of the National Institute of Health (PSI:Biology)-the Center for Membrane Proteins in Infectious Diseases (MPID) at ASU and Trinity College Dublin led by Petra Fromme, and the GPCR Network at Scripps led by Prof. Ray Stevens.
Fromme led the ASU group that helped plan the experiments, characterize the samples and assist with data collection. Other members of the ASU team include Daniel James, Dingjie Wang, Garrett Nelson, Uwe Weierstall, Nadia Zatsepin, Richard Kirian, Raimund Fromme, Shibom Basu, Christopher Kupitz, Kimberley Rendek, Ingo Grotjohann and John Spence.
|New technology, developed in the lab of Mark Hayes, using microscale electric field gradients now can tell the difference between good and bad bacteria in minutes from extremely small samples. Shown are generic E. coli and bacteria populations isolated on a microdevice.
December 2, 2013
Sorting good germs from bad, in the bacterial world
Arizona State University scientists have developed a microfluidic chip, which can sort good germs from bad.
Your intestines are home to about 100 trillion bacteria. That's more than the number of cells that comprise the entire human body. Armies of bacteria sneak into our bodies the moment we are born, uninvited but necessary guests.
For the most part, these bacteria are industrious and friendly. Some of them are even beneficial, helping with digestion and producing vitamins. A few miscreants, though, will kill us if we let them stay.
Sometimes the difference between harmless and harmful is miniscule. Take E. coli for instance. Billions of E. coli organisms live in the average person's intestines. They go about their business causing no trouble whatsoever. However, one particular strain of E. coli, O157:H7, causes about 2,000 hospitalizations and 60 deaths in the U.S. every year. The differences between this strain and others are detectable only at the molecular level.
But how do we separate friend from foe? Determining whether or not bacteria are harmful usually requires growing cultures from food or infected patients. This is a time-consuming process that must be carried out in a laboratory. Since an estimated 9.4 million cases of food-borne illness occur each year in the U.S., we stand to gain much from new technologies that can rapidly identify microorganisms.
Scientists at Arizona State University's School of Molecular Sciences, in the College of Liberal Arts and Sciences, have developed a new device that could significantly speed up the identification process for harmful bacteria and other microorganisms. The team, led by Professor Mark A. Hayes, hopes to create handheld, battery-operated devices that could deliver answers in minutes, instead of days.
Identification takes place within a microscopically small channel in a chip made from glass or silicone polymer. The microchannel features saw-tooth shapes that allow researchers to sort and concentrate microbes based on their unique electrical properties.
The phenomenon that makes this work is called dielectrophoresis, which involves an applied voltage that exerts force upon the bacteria. This force acts like a coin-sorter, causing bacteria to become trapped at different points along the channel. Where they stop, and at what voltage, depends on their molecular and electrical properties.
Using this approach, Hayes's team including graduate student, Paul V. Jones, has separated extremely similar bacteria-pathogenic and nonpathogenic strains within the single species, E. coli. Their results have recently been published in "Online First" on SpringerLink and in the journal Analytical and Bioanalytical Chemistry.
"The fact that we can distinguish such similar bacteria has significant implications for doctors and health officials," says Hayes. He explains, "that scientists have struggled to find ways to rapidly identify bacteria. E. coli O157:H7 is very similar in size and shape to other subtypes of the bacteria. But unlike many of the others it has the ability to produce shiga-like toxin, a protein that breaks down blood vessel walls in the digestive tract."
Fortunately, all of these bacterial strains also possess subtle, but telltale differences in the proteins and other molecules that they express on their surface. According to Professor Hayes, dielectrophoresis is well suited to probe these phenotypic differences.
The researchers used an ordinary strain of E. coli along with two pathogenic varieties. They injected the cells into each channel and simply applied voltage to drive the cells downstream. The geometric features of the channel shape the electric field, creating regions of different intensity. This field creates the dielectrophoretic force that allows some cells to pass, while trapping others based on their phenotype.
So far, the device has only been used to test pure cultures of bacteria, but they hope soon to test complex mixtures of particles that are found in nature or the human body.
The next step is to create cheap, portable devices that would enable point-of-care or field based analysis. Such a device would require no time-consuming culturing or other tests, which would allow rapid response to disease or contamination, hopefully saving lives.
This work was supported by the NIH National Institute of Allergy and Infectious Diseases (grant number: 5R03AI099740-02).
Jenny Green, firstname.lastname@example.org
School of Molecular Sciences
read "ASU researchers on verge of medical breakthrough" on KTAR News
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