Chemistry & Biochemistry News
|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
Department of Chemistry and Biochemistry
|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 Department of Chemistry and Biochemistry 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 Department of Chemistry and Biochemistry (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
Department of Chemistry and Biochemistry
|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 Department of Chemistry and Biochemistry 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 Department of Chemistry and Biochemistry 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 Department of Chemistry and Biochemistry 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
Department of Chemistry and Biochemistry
"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 Department of Chemistry and Biochemistry 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.
Sarah Auffret, firstname.lastname@example.org
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, Department of Chemistry and Biochemistry, 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.
Amelia Huggins, firstname.lastname@example.org
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.
Reach the reporter at email@example.com or follow her on twitter @kelciegrega
|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 Department of Chemistry and Biochemistry 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
Department of Chemistry and Biochemistry
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.
Skip Derra, email@example.com
"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 Department of Chemistry and Biochemistry 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 Department of Chemistry and Biochemistry, 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
Department of Chemistry and Biochemistry
read "ASU researchers on verge of medical breakthrough" on KTAR News
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