Caltech and UCSD Researchers Shed Light on How Proteins Find Their Shapes

The researchers bring together theoretical models and experimental data to explain protein folding

PASADENA, Calif.--Researchers from the California Institute of Technology (Caltech) and the University of California at San Diego (UCSD) have brought together UCSD theoretical modeling and Caltech experimental data to show just how amino-acid chains might fold up into unique, three-dimensional functional proteins.

Their insights were recently published in the February 10 issue of the Proceedings of the National Academy of Sciences (PNAS).

The paper details the matching of a series of protein-folding models created by the UCSD team (led by Peter Wolynes, UCSD professor of chemistry and biochemistry and physics) with experimental data gathered using a novel technique created by the Caltech team (led by Faculty Associate in Chemistry Jay Winkler and Harry Gray, Caltech's Arnold O. Beckman Professor of Chemistry and founding director of the Beckman Institute).

The Winkler-Gray method of watching proteins as they crumple and fold involves the use of a picosecond camera that captures fluorescent flashes as a laser pulse excites a donor probe, which emits light and transfers that light to an acceptor probe. The distance between the donor and acceptor change as the amino-acid chain transforms itself into a three-dimensional protein.

In the PNAS paper, the two groups combined the Caltech experimental technique--first described in a 2002 paper published in the Journal of the American Chemical Society--with Wolynes's protein-folding models to see if they could come up with the precise folding pattern of cytochrome c, a protein that is part of the mitochondrial electron-transfer chain that turns food into cellular energy.

At first the models and the experimental data seemed to be describing two entirely different things, according to Winkler. "The researchers had to account for charge-charge interactions between amino acids that appear to be important--the way that like charges repel and opposite charges attract," he explains. "And they had to consider the hydrophobic interactions--the way that oily parts of the proteins like to stick together but are repelled by the watery parts. When their models took account of these interactions, it fit the experimental data."

"It was the first time anyone has been able to develop a theoretical model able to account for the results we've been getting with our time-resolved energy-transfer experiments," adds Gray.

Other coauthors on the PNAS paper, entitled "Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles," are Patrick Weinkam from UCSD and Ekaterina Pletneva, formerly at Caltech and now at Dartmouth College.

This work was supported by grants from the National Institutes of Health and by a National Science Foundation Center for Theoretical Biological Physics grant.

Lori Oliwenstein

Self-Regulating Molecular "Transformers" Control the Intracellular Delivery of Proteins

PASADENA, Calif.--Scientists from the California Institute of Technology (Caltech) have uncovered the Transformer like properties of molecules responsible for carrying and depositing proteins to their correct locations within cells. The research could eventually lead to novel treatments for diseases that result from flaws in protein delivery as well as the development of new types of antibiotics.

Shu-ou Shan, an assistant professor of chemistry at Caltech, and her colleagues looked specifically at a pair of proteins that sort cellular proteins and deliver them to their destinations--a process that is essential for establishing and maintaining cellular organization. The proteins, known as the signal recognition particle (SRP) and the SRP receptor (SR), are responsible for shuttling more than a third of all cellular proteins to their targets, including the insulin protein. The SRP/SR system is present in all three kingdoms of life, from humans and other animals, to plants and fungi, to bacteria and primitive archaean organisms.

By tracking the movement of fluorescently tagged molecules, Shan and her colleagues were able to track the behavior of SRP and SR during the protein pick-up and delivery process.

They found that the binding of a protein cargo by the SRP molecule triggered the accelerated assembly of a molecular complex containing SRP, the cargo, and the SR protein. The SRP-SR complex then delivered the cargo to the cell membrane. Once there, the SRP-SR complex spontaneously changed its shape and deposited the cargo at the membrane, like a tiny Transformer toy morphing from a semi-truck delivering goods into a forklift that unloads them. The scientists described their discovery in a recent paper in the Proceedings of the National Academy of Sciences.

"The Transformer analogy is very appropriate," says Shan. "The 'truck' is able to sense that cargo has been loaded and starts the engine running without instructions from a driver. It can also sense that it has arrived at the destination and, without workers coming to unload the goods, is able to switch on another system to do that by itself." This self-sufficient system, she says, represents "a new way that biology builds switches to regulate complex cellular pathways."

Shan and colleagues also found that the presence of protein cargo delays the breakdown of a small-molecule energy carrier called guanosine triphosphate, or GTP, from which the SRP and SR harvest the energy to form a complex with each other and to undergo all their molecular transformations. "GTP hydrolysis is like a timer that allows the SRP-SR complex to exist for a specified period of time before turning it off. By delaying this timer, the SRP-SR complex persists about 10 times longer than it would without the cargo. This ensures that there is sufficient time for the cargo to be properly delivered to the membrane," Shan says.

"Understanding which steps are important for protein delivery by the SRP could allow the development of medications that prevent diseases that result from defects in the pathway," Shan says. For example, prion disease can be caused by tiny snippets of misfolded prion proteins that accumulate in the cytoplasm of cells when the SRP pathway does not work properly. The accumulation of cytoplasmic prions leads to the degeneration of neurons, and the eventual death of the affected organism."

The research could also lead to the development of novel artificial delivery systems that can shuttle particular proteins to specific locations, and may spur the design of new types of antibiotics that target the SRP protein in bacteria. Blocking the bacterial SRP will indeed kill bacteria, Shan says, but because humans have SRP proteins, it "will also likely affect the operation of cells in your body. Detailed mechanistic studies are required to figure out the difference between the mammalian and the bacteria SRP pathway, and find places to intervene where the bacterial SRP is uniquely susceptible."

Shan's paper, "Multiple conformational switches in a GTPase complex control co-translational protein targeting," was coauthored by Xin Zhang, a graduate student at Caltech, and Christiane Schaffitzel and Nenad Ban from the Swiss Federal Institute of Technology. The work was funded by the National Institutes of Health and the Swiss National Science Foundation.



Kathy Svitil

Caltech 4D Microscope Revolutionizes the Way We Look at the Nano World

PASADENA, Calif.-- More than a century ago, the development of the earliest motion picture technology made what had been previously thought "magical" a reality: capturing and recreating the movement and dynamism of the world around us. A breakthrough technology based on new concepts has now accomplished a similar feat, but on an atomic scale--by allowing, for the first time, the real-time, real-space visualization of fleeting changes in the structure and shape of matter barely a billionth of a meter in size.

Such "movies" of atomic changes in materials of gold and graphite, obtained using the technique, are featured in a paper appearing in the November 21 issue of the journal Science. (4D microscopy videos can be viewed at A patent on the conceptual framework of this approach was granted to the California Institute of Technology (Caltech) in 2006.

The new technique, dubbed four-dimensional (4D) electron microscopy, was developed in the Physical Biology Center for Ultrafast Science and Technology, directed by Ahmed Zewail, the Linus Pauling Professor of Chemistry and professor of physics at Caltech, and winner of the 1999 Nobel Prize in Chemistry.

Zewail was awarded the Nobel Prize for pioneering the science of femtochemistry, the use of ultrashort laser flashes to observe fundamental chemical reactions--atoms uniting into molecules, then breaking apart back into atoms--occurring at the timescale of the femtosecond, or one millionth of a billionth of a second. The work "captured atoms and molecules in motion," Zewail says, akin to the freeze-frame stills snapped by 19th-century photographer Eadweard Muybridge of a galloping horse (which proved for the first time that a horse does indeed lift all four hooves off the ground as it gallops) and other moving objects.

Snapshots of molecules in motion "gave us the time dimension," Zewail says, "but what we didn't have was the dimensions of space, the structure. We didn't know what the horse looked like. Did it have a long tail? Beautiful eyes? My dream since 1999 was to come up with a way to look not just at time but also at the spatial domain; to see the architecture of a complex system at the atomic scale, as it changes over time, be it for physical or biological matter."

Scientists can observe the static structure of objects with a resolution that is better than a billionth of a meter in length using electron microscopes, which generate a stream of individual electrons that scatter off objects to produce an image. Electrons are used to visualize the smallest of objects, on the atomic scale, because the wavelength of the radiation source used by a microscope must be shorter than the space between the atoms. This can be accomplished using electrons, and in particular--because the wavelength of an electron shrinks as its velocity increases--by electrons that have been accelerated to dizzying speeds.

But just having electrons isn't sufficient to capture the behavior of atoms in both space and time; the electrons have to be carefully doled out, so that they arrive at the sample at specific time intervals. Zewail and his colleagues have achieved this by introducing the fourth dimension of time into high-resolution electron microscopy, in what has been termed ultrafast "single-electron" imaging, where every electron trajectory is precisely controlled in time and space.

The resulting image produced by each electron represents a femtosecond still at that moment in time. Like the frames in a film, the sequential images generated by many millions of such images can be assembled into a digital movie of motion at the atomic scale.

As reported in the Science paper, Zewail and colleagues applied their new 4D electron microscopy to observe the behavior of the atoms in superthin sheets of gold and graphite. Graphite, the material in pencils, consists of layers of carbon atoms locked into a sheet-like array. The atoms move in a unique and coherent way on the femtosecond timescale.

However, the researchers found that on a slightly longer, picosecond (one thousandth of a billionth of a second) scale, the graphite nanosheets produce sound waves. In the images, they directly visualized the elastic movements of the sheets and determined the force holding them together, which is described by a stress-strain property known as "Young's modulus." The 4D movies produced from the frames revealed the behavior in space and time.

In a second paper in the current issue of the journal Nano Letters, Zewail and his colleagues described their visualization of the changes in a nanometer-thick graphite membrane on a longer time scale, up to a thousandth of a second. The researchers first blasted the sample with a pulse of heat. The heated carbon atoms began to vibrate in a random, nonsynchronized fashion. Over time, however, the oscillations of the individual atoms became synchronized as different modes of the material locked in phase, emerging to become a heartbeat-like "drumming." Digital video, slowed down more than a billion times, illustrates this nano-drumming mechanical phenomenon, which displays a well-defined resonance that is nearly 100 times higher than can be detected by the human eardrum.

"With this 4D imaging technique, atomic-scale motions, which lead to structural, morphological, and nanomechanical phenomena, can now be visualized directly, and hopefully understood," says Zewail, who is now expanding the research to biological imaging within cells in collaboration with Grant Jensen, an associate professor of biology at Caltech.

The researchers are currently using the 4D microscope to image the components of cells, such as proteins and ribosomes, the cellular machinery that makes proteins. They have already produced images of a stained rat cell and, more recently, of a protein crystal and cell in vitreous water. "The goal is to enhance the structural resolution in the images of these biomaterials by taking single-pulse snapshots before they move or deteriorate, and to follow their dynamics in real time," Zewail says.

In a recent commentary on the development, Sir John Thomas of Cambridge University, who is a world-renowned expert in electron microscopy, said the invention and its applications are "revolutionary." "The door is now open for myriad explorations in the physical and biological sciences," Thomas added.

"The sequences of images produced by this technique are remarkable," says David Tirrell, chair of Caltech's Division of Chemistry and Chemical Engineering. "They not only provide unprecedented insights into molecular and materials behavior--they do so in an especially satisfying fashion by allowing direct observation of complex structural changes in real space and real time. These experiments will lead us to fundamentally new ways of thinking about molecules and materials."

"Advances in imaging, concepts, and technology for visualization are fundamental to progress in diverse scientific and engineering fields," says Edward M. Stolper, Caltech's provost. "Caltech has made a commitment to leadership across the many physical and biological disciplines in which imaging plays a critical role. Ahmed's pioneering work is trailblazing new frontiers of science and technology."

Two centers supported the development of this technology: the Laboratory for Molecular Science, funded by the National Science Foundation, and the Physical Biology Center, funded by Gordon and Betty Moore Foundation. The work was also supported by grants from the Air Force Office of Scientific Research, the National Science Foundation, and the National Institutes of Health.



Kathy Svitil

Four Caltech Faculty Members Named Among 100 Chemical Engineers of the Modern Era

American Institute of Chemical Engineers lauds Frances Arnold, Mark Davis, Julia Kornfield, and John Seinfeld

PASADENA, Calif.--Four members of the 11-member chemical engineering faculty at the California Institute of Technology (Caltech) were honored by the American Institute of Chemical Engineers (AIChE) in their list of 100 Chemical Engineers of the Modern Era, published in the October issue of their magazine, Chemical Engineering Progress.

"Now in its second century, the chemical engineering profession--like the Institute--has been shaped and sustained by the achievements, leadership and imagination of thousands of engineers," the AIChE wrote in introducing its list.

The four Caltech chemical engineers named were

* Frances H. Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering and Biochemistry, who was recognized for "research on engineering biological systems, particular proteins and genetic regulatory networks, (e.g., using novel enzymes to catalyze cellulose hydrolysis)." The AIChE also noted that Arnold is the only woman to have been elected to all three branches of the National Academies: the National Academy of Engineering (in 2000), the Institute of Medicine (in 2004), and the National Academy of Sciences (in 2008).

* Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering, who was recognized for "pioneering work in new catalytic materials and chemical sensors using ceramics and electronic materials."

* Julia A. Kornfield, professor of chemical engineering, who was recognized for "work on polymer blend dynamics; flow alignment of liquid-crystalline and block polymers; physical aspects of new biomedical materials."

* John H. Seinfeld, the Louis E. Nohl Professor and professor of chemical engineering, who was recognized for "developing first models describing urban air quality" and for being "one of first to describe linkage between urban ozone and global climate change."

"I'm very proud that my colleagues have been recognized in this way by the most important professional organization in the field of chemical engineering. Their selection reflects well on the Caltech approach to things, which is to stay small while maintaining the highest possible standards in education and research," says David Tirrell, chair of Caltech's Division of Chemistry and Chemical Engineering.

"At Caltech, I'm inspired to work on the hardest problems, because the students here can solve them," adds Frances Arnold. "This honor, awarded to almost half our department, certainly recognizes that."

# # #


Lori Oliwenstein
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Caltech Engineers Build First-Ever Multi-Input "Plug-and-Play" Synthetic RNA Device

Could one day be used to detect tumor cells or create targeted gene therapies

PASADENA, Calif.--Engineers from the California Institute of Technology (Caltech) have created a "plug-and-play" synthetic RNA device--a sort of eminently customizable biological computer--that is capable of taking in and responding to more than one biological or environmental signal at a time.

In the future, such devices could have a multitude of potential medical applications, including being used as sensors to sniff out tumor cells or determine when to turn modified genes on or off during cancer therapy.

A synthetic RNA device is a biological device that uses engineered modular components made of RNA nucleotides to perform a specific function--for instance, to detect and respond to biochemical signals inside a cell or in its immediate environment.

Created by Caltech's Christina Smolke, assistant professor of chemical engineering, and Maung Nyan Win, postdoctoral scholar in chemical engineering, the device is made up of modules comprising the RNA-based biological equivalents of engineering's sensors, actuators, and information transmitters. These individual components can be combined in a variety of different ways to create a device that can both detect and respond to what could conceivably be an almost infinite number of environmental and cellular signals.

This modular device processes these inputs in a manner almost identical to the logic gates used in computing; it can perform AND, NOR, NAND, and OR computations, and can perform signal filtering and signal gain operations. Smolke and Win's creation is the first RNA device that can handle more than one incoming piece of biological information. "There's been a lot of work done in single-input devices," notes Smolke. "But this is the first demonstration that a multi-input RNA device is possible."

Their work was published in the October 17 issue of the journal Science.

The modular--or plug-and-play--nature of the device's design also means that it can be easily modified to suit almost any need. "Scientists won't have to redesign their system every time they want the RNA device to take on a new function," Smolke explains. "This modular framework allows you to quickly put a device together, then just as easily swap out the components for other ones and get a completely different kind of computation. We could generate huge libraries of well-defined sensors and assemble many different tailored devices from such component libraries."

Although the work in the Science paper was done in yeast cells, Smolke says they have already shown that they can translate to mammalian cells as well. This makes it possible to consider using these devices in a wide variety of medical applications.

For instance, ongoing work in Smolke's laboratory is looking at the packaging of these RNA devices--configured with the appropriate sensor modules--in human T cells. The synthetic device would literally be placed within the cell to detect certain signals--say, one or more particular biochemical markers that are given off by tumor cells. If those biomarkers were present, the RNA device would signal the T cell to spring into action against the putative tumor cell.

Similarly, an RNA device could be bundled alongside a modified gene as part of a targeted gene therapy package. One of the problems gene therapy faces today is its lack of specificity--it's hard to make sure a modified gene meant to fix a problem in the liver reaches or is inserted in only liver cells. But an RNA device, Smolke says, could be customized to detect the unique biomarkers of a liver cell--or, better yet, of a diseased liver cell--and only then give the modified gene the go-ahead to do its stuff.

The work described in this paper, "Higher-Order Cellular Information Processing with Synthetic RNA Devices," was supported by grants from the Center for Biological Circuit Design at the California Institute of Technology, the Arnold and Mabel Beckman Foundation, and the National Institutes of Health. Smolke and Win have a patent application pending on their synthetic RNA device.

For more information on Smolke's work, visit

Lori Oliwenstein
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Caltech Researcher Awarded $10 Million Grant

PASADENA, Calif.-- Brian M. Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry at the California Institute of Technology (Caltech), has been awarded a $10 million grant from the King Abdullah University of Science and Technology (KAUST).

Stoltz, whose work is focused on developing new strategies for the synthesis of complex molecules with interesting structural, biological, and physical properties that may lead to useful biological and medical applications, is one of 12 international scientists chosen to receive the award as part of the KAUST Global Research Partnership (GRP) Investigator competition. The GRP program is designed to fund research in areas of science and technology that are of particular importance to Saudi Arabia and the region, such as water desalination, renewable and sustainable next-generation energy sources, salt-tolerant plants, durable and environmentally friendly construction materials, and solar technology.

Each investigator was scrutinized by a panel of 14 world-renowned scientists, including Caltech's former provost Steven E. Koonin, chief scientist at British Petroleum, and evaluated based on their record of achievement to date and the relevance of their proposed research to the mission areas of KAUST, which include energy and environment; materials science and bioengineering; biosciences; and applied mathematics and computational science.

Stoltz was recognized for his efforts to discover and develop new oxidation reaction processes of potential utility for the chemical, polymer, and pharmaceutical industries. The new methods employ organometallic catalysts in conjunction with molecular oxygen, instead of the toxic metals that are normally used. These new catalytic reactions also provide avenues of reactivity that are simply unavailable using older techniques.

"Caltech is honored that KAUST and its committee of esteemed scientists selected Brian Stoltz after their extensive search for the world's most promising science and technology researchers," says Caltech president Jean-Lou Chameau. "This generous award will significantly advance Brian's efforts in chemical synthesis and nontoxic catalysts, and also reminds us of the global impact that our scientists are making with their research," adds Chameau.

"This is an enormous boost for our research program and my students and I couldn't be happier that the KAUST GRP has entrusted us with this honor," Stoltz says. "I am excited to work with KAUST and be a part of this very unique endeavor. It will be an exciting time here and at KAUST!"

Each investigator will spend at least three weeks per year on the KAUST campus in Saudi Arabia, participating in the research and academic life of the University.

KAUST is an international graduate-level research university, "dedicated to inspiring a new age of scientific achievement in the Kingdom, across the region and around the globe," being built on the Red Sea at Thuwal, approximately 50 miles north of Saudi Arabia's second-largest city, Jeddah. The 36-million-square-meter core campus is set to open in September 2009. For more information, visit

With an outstanding faculty, including five Nobel laureates, and such off-campus facilities as the Jet Propulsion Laboratory, Palomar Observatory, and the W. M. Keck Observatory, the California Institute of Technology is one of the world's major research centers. Caltech offers instruction in science and engineering for a student body of approximately 900 undergraduates and 1,200 graduate students who maintain a high level of scholarship and intellectual achievement. Caltech is a private university in Pasadena, California. For more information, visit

Kathy Svitil
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Caltech Engineers Build Mini Drug-Producing Biofactories in Yeast

PASADENA, Calif.-- Researchers at the California Institute of Technology have developed a novel way to churn out large quantities of drugs, including antiplaque toothpaste additives, antibiotics, nicotine, and even morphine, using mini biofactories--in yeast. 

A paper describing the research, now available online, will be featured as the cover article of the September issue of Nature Chemical Biology.

Christina D. Smolke, an assistant professor of chemical engineering at Caltech, along with graduate student Kristy Hawkins, genetically modified common baker's yeast (Saccharomyces cerevisiae) so that it contained the genes for several plant enzymes. The enzymes allow the yeast to produce a chemical called reticuline, which is a precursor for many different classes of benzylisoquinoline alkaloid (BIA) molecules. The BIA molecules are a large group of chemically intricate compounds, such as morphine, nicotine, and codeine, which are naturally produced by plants.

BIA molecules exhibit a wide variety of pharmacological activities, including antispasmodic effects, pain relief, and hair growth acceleration. Other BIAs have shown anticancer, antioxidant, antimalarial, and anti-HIV potential.

"There are estimated to be thousands of members in the BIA family, and having a source for obtaining large quantities of specific BIA molecules is critical to gaining access to the diverse functional activities provided by these molecules," says Smolke, whose lab focuses on using biology as a technology for the synthesis of new chemicals, materials, and products. However, the natural plant sources of BIAs accumulate only a small number of the molecules, usually "end products" like morphine and codeine that, while valuable, can't be turned into other compounds, thus limiting the availability of useful new products.

To their reticuline-producing yeast, Smolke and Hawkins added the genes for other enzymes, from both plants and humans, which allowed the yeast to efficiently generate large quantities of the precursors for sanguinarine, a toothpaste additive with antiplaque properties; berberine, an antibiotic; and morphine.

The researchers are now in the process of engineering their yeast so that they will turn these precursor molecules into the final, pharmacologically useful molecules. "But even the intermediate molecules that we are producing can exhibit important and valuable activities, and a related area of research will be to examine more closely the pharmacological activities of these metabolites and derivatives now that pure sources can be obtained," says Smolke, who estimates that her system could be used for the large-scale manufacture of BIA compounds in one to three years.

Smolke and Hawkins also plan to extend their research to the production of BIAs that don't normally exist in nature.

"If one thinks of these molecules as encoding functions that are of interest to us, the ability to produce nonnatural alkaloids will provide access to more diverse functions and activities. By expanding to nonnatural alkaloids, we can search for molecules that provide enhanced activities, new activities, and not be limited by the activities that have been selected for in nature," says Smolke.

"Our work has the potential to result in new therapeutic drugs for a broad range of diseases. This work also provides an exciting example of the increased complexity with which we are engineering biological systems to address global societal challenges," she says.

The research was supported by the Center for Biological Circuit Design at Caltech and the National Institutes of Health.


Kathy Svitil
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Caltech Scientists Awarded $20 Million to "Power the Planet"

PASADENA, Calif.--In the dreams of Harry Gray, Beckman Professor of Chemistry at the California Institute of Technology, the future energy needs of the world are met with solar-fuel power plants. Now, a $20 million award from the Chemical Bonding Center (CBC), a National Science Foundation (NSF) Division of Chemistry program, will help bring this dream one step closer to reality.

In 2005, NSF granted three Phase I CBC awards. Gray formed a group of Caltech and MIT scientists who spent the $1.5 million and three years of Phase I conducting initial research and establishing public outreach plans for their idea.

Of the three Phase I projects, Caltech's is the only one to advance to Phase II, a $20 million, five-year extension. "We have added outstanding investigators from many other institutions to our Caltech-MIT team in order to ramp up our efforts in Phase II of the 21st century grand challenge to make solar fuels using materials made from Earth-abundant elements," says Gray.

In Phase I, the Caltech-MIT alliance, called "Powering the Planet," proposed to develop nanoscale materials to make fuel from sunlight and water. They designed a nanorod-catalyst water splitter that incorporates a membrane to separate the oxygen- and hydrogen-making parts of the system.

Nathan Lewis, Caltech's Argyros Professor and professor of chemistry, and chemist Bruce Brunschwig, a Member of Caltech's Beckman Institute (BI) and Director of the Materials Resource Center for the BI, headed a group of students and postdocs who began working on a silicon nanorod-studded plastic sheet to harvest sunlight. The hydrogen-making catalyst team was headed by Gray, Jay Winkler (a Caltech faculty associate in chemistry), and Jonas Peters (a former Caltech chemistry professor now at MIT). Research with the goal of finding efficient catalysts for the oxidation of water to oxygen was led by MIT scientists Dan Nocera, a former graduate student of Gray's, and Christopher Cummins.

With a conceptual design in place, and with promising results in all three investigation areas, the alliance expanded--18 senior researchers at 12 institutions signed on to compete for Phase II of the CBC award and participate in testing and refining the nanoscale water-splitting device.

Luis Echegoyen, Director of the NSF Division of Chemistry, says, "The Division of Chemistry is pleased and excited to establish this new CBC devoted to elucidating some basic science aspects of solar energy research. This center and its excellent team of researchers will enable NSF to partner with the scientific community to explore fundamental aspects of solar-driven splitting of water into hydrogen and oxygen."

The CBC Program is designed to support the formation of centers that can address long-term, high-risk, and high-impact basic chemical research problems. The centers are expected to be responsive to rapidly emerging opportunities and make full use of cyberinfrastructure to enhance collaborations.

"We are excited about our prospects, as we are lucky to have a very talented and dedicated group of students and postdocs who are ready and able to tackle the fundamental chemistry problems that must be solved before it will be feasible to produce clean solar fuels on a large scale," Gray adds. The Phase II award may be extended for an additional five years.

For more information on the award, visit


Elisabeth Nadin

Zhen-Gang Wang Receives Feynman Prize for Excellence in Teaching

PASADENA, Calif.--Zhen-Gang Wang favors the tried-and-true chalkboard for his classroom lectures on thermodynamics and polymer physics. The clarity of these lessons and the admiration of his students have won him this year's Feynman Prize for Excellence in Teaching at the California Institute of Technology.

"What I teach is traditional topics, so I use traditional means," remarks Wang, a professor of chemical engineering at Caltech, adding that he was very pleasantly surprised by the news. "Excellent board work" is just one of many praises listed in student evaluations of Wang's classes. "He engaged me as no lecturer ever had before," says Andrew Downard, who came to Caltech from Notre Dame University for graduate studies in chemical engineering. "The class is a journey to seek the truth with basic postulates and a passionate expert in the field to help steer us."

The Feynman Prize is Caltech's most prestigious teaching honor. With it comes a $3,500 cash award and an equivalent raise in annual salary. Winners are selected by a committee of students, former winners, and other faculty.

Wang started teaching at Caltech 17 years ago, having never before taught or even served as a teaching assistant. He knew he was in trouble after his first class, in statistical mechanics: "The level was unreasonably high--the scores on exams were very low. I learned over the years to adjust the level of the presentation," he remembers. "You have to really understand the material well, from several different angles, and then find the best angle that would be suitable for the students."

The hard work paid off, and across the board Wang's students admire his "uncanny ability to cut to the heart of a question and provide an answer based on fundamentals," according to one. They appreciate how he challenges them to sharpen their questions, and how he "sets the intellectual bar high" but gives them the means to reach it.

"I love teaching," says Wang, adding that he finds a sense of nobleness through training the next generation of scientists and engineers. "I enjoy research and I am devoted to it, but it feels more like a hobby. But my research is theoretical; it doesn't have an immediate impact on society. Through teaching, I feel like I'm having a more direct impact."

"Zhen-Gang is already quietly becoming one of the legends of Caltech," raves Julie Kornfield, a professor of chemical engineering at Caltech who nominated Wang for the prize. "He profoundly affects our students and transforms the way they think. To me he represents the essence of what Caltech is all about."

The Feynman Prize is named after legendary Caltech physics professor Richard Feynman, who wrote, "I don't believe I can do without teaching," in his book Surely You're Joking, Mr. Feynman! The prize is endowed through the generosity of Ione and Robert E. Paradise and an anonymous local couple, to annually honor a professor who demonstrates unusual ability, creativity, and innovation in undergraduate and graduate classroom or laboratory teaching.

Elisabeth Nadin
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Caltech Professor Frances H. Arnold Elected to the National Academy of Sciences

PASADENA, Calif.-- Frances H. Arnold of the California Institute of Technology has been elected to the National Academy of Sciences, an honor considered to be one of the highest accolades in the scientific world. Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering and Biochemistry, is also a member of the National Academy of Engineering and the Institute of Medicine, making her one of only eight living individuals to have been elected to all three branches of the National Academies, and the only woman.

Arnold was elected for integrating fundamentals in molecular biology, genetics, and bioengineering to the benefit of life science and industry. Her research has revolutionized protein engineering and its applications to biotechnology, addressing central issues in protein design and the evolution of new biocatalysts.

She is one of the pioneers in the use of "directed evolution" to improve proteins and other biological molecules for commercial applications. Directed evolution applies the principles of breeding, but to molecules rather than animals or plants. Using these methods, Arnold has been able to generate proteins with a variety of useful features, like improved stability and the ability to function in nonnatural environments.

The practical applications of this research are very broad and include making enzymes that can effectively break down cellulose, the key structural component of plant cell walls, which would allow the efficient production of cellulosic biofuels.

"I am thrilled to have this recognition, and validation, of our efforts to use evolution to engineer biology," Arnold says. "At Caltech I have been able to work with great students and colleagues from disparate disciplines, who have helped me find new ways to look at problems. Caltech is both immensely stimulating and very supportive."

"Frances's work has changed the way we think about biological engineering, and her methods have been adopted by hundreds of laboratories around the world. It's a beautiful example of a new idea that proved to be almost immediately applicable to a broad range of fundamental and practical problems," says David A. Tirrell, the Ross McCollum-William H. Corcoran Professor and professor of chemistry and chemical engineering, and chair of the Division of Chemistry and Chemical Engineering at Caltech. "We're very proud of what Frances and her students have accomplished."

The National Academy of Sciences is a private organization of scientists and engineers dedicated to the furtherance of science and its use for the general welfare. It was established in 1863 by a congressional act of incorporation signed by Abraham Lincoln that calls on the academy to act as an official adviser to the federal government, upon request, in any matter of science or technology.

The election of Arnold brings the total Caltech membership to 75 faculty and three trustees.

Kathy Svitil
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