Three New Howard Hughes Medical Institute Investigators Named

PASADENA, Calif.--Every three years, the Howard Hughes Medical Institute (HHMI) appoints the nation's most creative biomedical scientists as investigators, giving them millions of dollars to unfetter their ambitious research plans. This year, three of the 56 newly named HHMI investigators come from the California Institute of Technology.

David Chan, Michael Elowitz, and Grant Jensen were each chosen for their potential to "bring new and innovative ways of thinking about biology to the HHMI community," says Thomas R. Cech, president of HHMI. "They are poised to advance scientific knowledge dramatically in the coming years, and we are committed to providing them with the freedom and flexibility to do so," he adds.

Chan, an associate professor of biology, specializes in how mitochondria--often called the powerhouses of biological cells--interact with each other. While this field, called mitochondrial dynamics, is still in its infancy, its implications are far-reaching. Chan has found that the loss of mitochondrial dynamics in mice, for example, leads to defects in placental tissue, in neurons in the cerebellum, and in skeletal muscle. He also studies the connection between accumulating damage in human mitochondria and the process of aging.

"I was surprised and very honored to be selected as an HHMI investigator. I am deeply grateful to advisors and colleagues who supported my career and encouraged me to apply," Chan says. "This appointment will help us to aggressively pursue ongoing projects in the lab, and also to expand into a couple of new, exciting areas in mitochondrial biology."

Biology and physics form a natural combination for Michael Elowitz, who builds genetic circuits and inserts them into living bacteria. The bacteria execute the tasks they are programmed to do, such as blinking on and off like a twinkling light. As an assistant professor of biology and applied physics and a Bren Scholar, Elowitz is fundamentally interested in how cells' own genetic circuits dictate what type of cells they become.

In work that overturned the steadfast notion that genes and networks of genes operate in a predictable and fixed fashion, he and his colleagues showed that key properties of the cell--like how actively it turns out different proteins--are intrinsically random. To show that randomness is used to more accurately control the shapes and patterns that make organisms work, Elowitz is turning to larger and more complex animal cells. "I'm grateful to HHMI for the amazing opportunity this appointment presents to focus as much as possible on research. The funds will enable us to explore new directions, especially allowing us to expand approaches we've previously developed primarily in bacteria to mammalian cells."

Assistant Professor of Biology Grant Jensen combines emerging electron microscope technologies with biology to image biological structures that could, until recently, only be imagined. One example of such a structure is the motor that drives the flagella of spirochete bacteria. Jensen has also shown key structures of proteins in HIV and has demonstrated that, contrary to long-held convictions, bacteria have a cytoskeleton.

Going beyond the static images, Jensen has created animations for biological processes. Applying the same technology used in movies, he showed the process of HIV maturation and bacterial motility. "It has been exciting to begin thinking of the additional research we will now be able to do," says Jensen of the award. "We're going to move more quickly now into complementing our current electron microscopical methods with light microscopy, and also begin modeling our hypotheses computationally."

The selection of Chan, Elowitz, and Jensen brings to 10 the total number of HHMI investigators at Caltech, eight of whom are among the 36 total faculty of the Division of Biology. The HHMI promotes its principle of "people, not projects" by appointing scientists as investigators, rather than awarding research grants. Investigators are urged to take risks, to explore unproven avenues, and to embrace the unknown, even if it means uncertainty or the chance of failure.

A nonprofit medical research organization, HHMI was established in 1953 by the aviator-industrialist Howard Hughes. The institute, headquartered in Chevy Chase, Maryland, is one of the largest philanthropies in the world, with an endowment of $18.3 billion at the close of the 2007 fiscal year. HHMI spent $599 million in support of biomedical research and $86 million for support of a variety of grants programs in fiscal year 2007.

For more information on HHMI and this year's investigator's, please visit: http://www.hhmi.org/news/20080527.html

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Elisabeth Nadin
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New Rosen Bioengineering Center Funded

PASADENA, Calif.- Seeing a burgeoning new research field at the interface of biology and engineering, the Benjamin M. Rosen Family Foundation of New York has donated $18 million to the California Institute of Technology to establish the Donna and Benjamin M. Rosen Bioengineering Center.

"Ben and Donna Rosen are recognizing how critical bioengineering is to the future of Caltech, science, and society, and they also appreciate the power an endowment can have in sustaining such an initiative," said Caltech President Jean-Lou Chameau. "The Institute is fortunate to have them as friends."

The Rosen Center will advance both basic scientific exploration and development of engineering analysis and synthetic approaches. Innovations in these areas are resulting in rugged and inexpensive diagnostic devices, in new insights into the functioning of the heart, and in the engineering of molecular devices capable of recognizing and responding to disease processes in individual cells.

Bioengineering developed at Caltech in recognition of the fact that biology is becoming more accessible to approaches that are commonly used in engineering, including mathematical modeling, systems theory, computation, and abstraction-based synthesis. At each level of organization, from the molecule to the cell to the organ, the accelerating pace of discovery in the biological sciences reveals new design principles that are of fundamental importance in understanding living organisms, and that will have important practical applications in future synthetic biological and biomedical systems and devices.

"Bioengineering arose at Caltech from the grassroots efforts of a handful of committed faculty coming together to establish a graduate option with great enthusiasm," said Scott Fraser, the Anna L. Rosen Professor of Biology and professor of bioengineering, who will lead the new center. "This gift will endow the program allowing it to foster the most innovative collaborative research. Such funding fuels innovation by offering support to venturesome efforts far earlier than would be possible through conventional granting agencies."

"There are a few times in history when diverse sciences, technologies and researchers fortuitously come together at the same time and at the same place to make possible great achievements for mankind," said Rosen. "This is one of those times, and Caltech is one of those places. We're honored to be able to play a small part in helping start this exciting new Caltech Bioengineering Initiative."

According to Ed Stolper, Caltech's provost, "Our current challenge is to provide an intellectual and programmatic focus for our growing teaching and research programs in bioengineering, spanning synthetic, systems, and computational biology; biomechanics and bio-inspired design; and development of novel biotechnologies. The Rosen Center will provide such a focus and critical support for these activities, which span many of the Institute's existing programs."

"Caltech's Bioengineering Center will foster the foundational work that will blossom into the next generation of tissue regeneration and diagnostic instrumentation," said Fraser. "The results of these innovations will make tools once considered too futuristic for anything but science fiction films into practical devices that can be carried in a physician's rear pocket."

Ben Rosen was founding chairman of Compaq Computer Corp. and a founding partner of Sevin Rosen Funds, a venture capital firm that has provided initial financing for more than 100 technology companies. Previously, he was vice president and senior electronics analyst at Morgan Stanley & Co., and before that he was an electronics engineer at Raytheon and Sperry Gyroscope. In 1992, Computerworld chose Rosen as one of 25 people in the computer industry "who changed the world." Rosen joined Caltech's board of trustees in 1986 and became chairman in 2001. He is also a member of the board of overseers and managers of Memorial Sloan-Kettering Cancer Center, a member of the board of overseers of Columbia Business School, and a director of the New York Philharmonic. Rosen earned a bachelor's degree in electrical engineering at Caltech in 1954. He also earned a master's in electrical engineering from Stanford and an MBA from Columbia University.

Donna Rosen was the former owner/director of Galerie Simonne Stern in New Orleans for 23 years until she moved to New York in 2002. She pioneered the New Orleans Warehouse District as the "Art District of New Orleans." She is a national trustee of the New Orleans Museum of Art; vice chairman of the board of American Friends of the British Museum; board member of The Society of Memorial Sloan-Kettering Cancer Hospital; and trustee of Second Stage Theater.

 

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Jill Perry
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One of Five Centers of Excellence for Predictive Science

PASADENA, Calif.--With a $17 million grant from the National Nuclear Security Administration (NNSA), the California Institute of Technology becomes one of five new centers of excellence that will focus on the emerging field of predictive science.

Michael Ortiz, the Dotty and Dick Hayman Professor of Aeronautics, professor of mechanical engineering, and director of Caltech's new Predictive Science Academic Alliance Program (PSAAP) Center, says Caltech will focus its efforts on the high-energy density dynamic response of materials, with demonstrations of hypervelocity impact response.

Hypervelocity impact is central to a number of scientific and application areas, including the design of protective shields for space structures and the understanding of meteorite impact cratering, Ortiz says. Accurate computer simulation is critical to the understanding of experiments that involve velocities reaching 10 kilometers per second, pressures in the megabar range, and extraordinarily high temperatures and deformation rates.

"The range of complex physics that is set in motion during hypervelocity impact is staggering," Ortiz remarks. "It includes melting, vaporization, and plasmas; hydrodynamic instabilities, mixed-phase flows, and mixing; and fracture, fragmentation, spall, and ejecta.

"The modeling and simulation of each of these phenomena in isolation is a scientific challenge in itself, but the predictive simulation of their coupled integral behavior is truly at the grand-challenge level and provides an exceedingly exacting test of predictive science."

Predictive science is the application of verified and validated computational simulations to predict the behavior of complex systems where routine experiments are not feasible. The research effort, which involves Caltech and four other selected PSAAP centers, will focus on unclassified applications of interest to NNSA and its three national laboratories: Lawrence Livermore National Laboratory, Los Alamos National Laboratory, and Sandia National Laboratories.

"At the core of this game-changing 'predictive science' paradigm shift is the ability to quantify uncertainties in the performance of complex systems by means of concerted and highly integrated experimental, computational, and analytical programs," Ortiz remarks.

The PSAAP centers, named by NNSA on March 7, will develop models and software for their large-scale simulations, as well as methods associated with the emerging disciplines of verification and validation and uncertainty quantification. The centers will be administered by the office of Advanced Simulation and Computing (ASC), which has funded the ASC Center at Caltech for the past 10 years.

"Caltech is in a unique position to advance the field of predictive science because of its culture of close interdisciplinary work among its faculty and research groups, exemplified by the highly successful ASC center led by Dan Meiron, and because of its longstanding tradition of approaching modeling and simulation at its most fundamental level," Ortiz says.

Experiments will be performed at experimental facilities in Caltech's Graduate Aeronautical Laboratories (GALCIT), including the newly-constructed Small Particle Hypervelocity Impact Range (SPHIR), notes Ares Rosakis, the von Kármán Professor of Aeronautics, professor of mechanical engineering, and director of GALCIT.

The executive director of Caltech's PSAAP Center is Mark Stalzer, executive director of Caltech's Center for Advanced Computing Research (CACR). The PSAAP Center will coordinate activities in areas including computational fluid dynamics, led by Dan Meiron, the Jones Professor of Applied and Computational Mathematics and Computer Science; computational science and engineering, led by CACR's principal computational scientist, Michael Aivazis; experimental science, led by Rosakis; solid dynamics and materials, led by Ortiz; and uncertainty quantification, led by Houman Owhadi, assistant professor of applied and computational mathematics and control and dynamical systems.

For further details on PSAAP, visit http://www.sandia.gov/NNSA/ASC/univ/psaap.html. 

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Elisabeth Nadin
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Mechanical Engineers Defy Gravity

PASADENA, Calif., and Cape Canaveral, Fl.--On the day that California Institute of Technology mechanical-engineering students will fling projectiles through the air in their annual design competition, two Caltech mechanical-engineering alumni will hurtle through space on the shuttle Endeavor.

The theme of this year's ME 72 Engineering Design Contest, the culmination of an engineering design laboratory for undergraduate students, is "fire and fly." It is fitting for a day on which astronauts and Caltech alumni Garrett Reisman and Robert Behnken lift off on the Endeavor space shuttle as part of a seven-man team en route to the International Space Station. The competition will be held on Tuesday, March 11, at 1 p.m. on Caltech's North Athletic Field, and the shuttle is scheduled for liftoff from Cape Canaveral, Florida.

Chris Brennen, Caltech's Hayman Professor of Mechanical Engineering, helped guide the ME 72 students through their test phases. He'll be at the shuttle launch on the day of their competition, but he remarks, "I was deeply torn between attending the space-shuttle launch and the ME 72 final contest." Reisman was his former student who became a close friend and married another mechanical engineering grad, Simone Francis.

Reisman, a space station flight engineer, will remain at the International Space Station for about six months and Behnken will return home after 16 days in orbit. A third Caltech alumnus, Greg Chamitoff, will then climb aboard Endeavor for the next launch, scheduled for March 28.

Brennen has close ties to NASA. He advised the agency on the shuttle's liquid-oxygen pumps and developed a lab at Caltech for creating and testing the main engine turbo pumps. When that facility was decommissioned several years ago, NASA disassembled it and moved it to the Marshall Space Flight Center in Huntsville, Alabama.

Brennen has spent much of his career investigating phenomena related to fluid flow, which he says was particularly useful in prepping students for ME 72 this year. "This year's ME 72 is different from previous contests because it involves some aerodynamics and fluid dynamics. It requires significantly more analysis of the mechanics of the device and the flight of the projectile in order to maximize the performance," he says.

On contest day, Brennen leaves the students in the hands of Joel Burdick, a professor of mechanical engineering and bioengineering at Caltech, who also helped them prepare. "We've had two contests already and tested and made adjustments. They're ready to go," Brennen says.

The competition centers on two basic constructions. The first is a ground-level launching device. The second is its 50-gram payload, "a projectile or flying device that will rise from a ground-level launcher, fly over a rope hurdle and then glide or be projected as far as possible over clear ground," according to the project description.

What happens after launch will be anybody's guess. In accordance with ME 72 tradition, the students may turn their machines on each other, navigating the airborne projectiles via remote control to tackle opponents' devices. According to the contest rules, "special admiration and an extra bonus" go to those payloads that land in a specially marked, two-meter-wide circular region beyond the basic target zone.

For further contest specifications, visit http://robotics.caltech.edu/~me72/. For more on Endeavor, go to http://www.nasa.gov/mission_pages/shuttle/main/. 

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Elisabeth Nadin
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New Method for Creating Tough Metallic Glass Composites

PASADENA, Calif.--Scientists at the California Institute of Technology have developed a new strategy for creating "liquid metal" that makes it able to bend significantly without breaking, while retaining a strength twice that of titanium. It is among the toughest, or least brittle, known materials, and could be used anywhere that strong metal alloys are traditionally found, but may prove most useful in the aerospace industry, where lower density means fuel savings.

When commercialized metallic glass known as Liquidmetal and Vitreloy hit the market several years ago in the forms of golf clubs and baseball bats, it was too brittle to withstand much duress. Now, says Douglas Hofmann, a Caltech materials science graduate student and lead author of a paper presenting the method for making the new material, it can be made to flex and can be produced at relatively low cost. "Metallic glasses now have among the highest toughness of any materials," he says.

Like window glass, metallic glass has no crystalline structure, but it is made with combinations of zirconium, titanium, copper, nickel, platinum, or other metals. Although the random arrangement of elements makes the material as strong as some of the strongest known metals, it also makes it very brittle. Most other metals deform plastically, meaning that under a heavy load, the deformation before ultimate fracture is permanent. Metallic glass behaves like an elastic band, which regains its original shape when released, but snaps when stretched past a certain point. A piece of metallic glass with any substantial thickness shattered easily when it was bent, and, Hofmann points out, "you couldn't build a bridge out of it. It breaks with no visual precursor.

"Many researchers in metallic glasses are trying to make them useful in structural applications," Hofmann says. He and his colleagues at Caltech have finally accomplished exactly that. They experimented with different combinations of metals to create a new version by manipulating the ratios of starting materials. They were guided by previous work by coauthor William Johnson, Caltech's Mettler Professor of Engineering and Applied Science, and his collaborators. Over the past two decades, these scientists had found that ductility--the ability of a material to deform in tension before breaking--was linked to the formation of branching, crystalline structures called dendrites within the metallic glass.

The team experimented first with the size of the dendrites. Hofmann and Johnson started by noting that when metallic glasses are bent, 10-nanometer-wide features called shear bands rip right through glass that is thicker than one millimeter, but are stabilized in thin glass. "The bending experiments told us that the size of the particles we need to add is proportional to the length scale of the shear bands before they become catastrophic," Hofmann describes.

In this time of exploding interest in nanotechnology, Hofmann was surprised to find that the dendrites had to be on the order of hundreds of microns in size, many thousands of times the size of the shear bands. The second major insight was that they also had to be softer than the surrounding metallic glass.

Because they are crystalline, the dendrites deform plastically, and their size blocks a single shear band from growing into a catastrophic crack. "It takes more energy to move a shear band forward than it takes to form a new shear band," notes Hofmann. "We took an alloy that broke with one shear band and made it make countless shear bands.

"We took a metallic glass, which is considered a brittle material, and showed that by making a designed composite out of it, we can span the entire space of toughness," Hofmann remarks. "The tougher it is, the harder it is to drive a crack through it. Now we have ductility and toughness," he claims.

Because the new metallic glass is tough and strong and has relatively low density, its obvious applications would be in any structure that incorporates titanium. In aerospace technology, these properties are crucial to minimizing weight and saving fuel costs.

But, says Hofmann, "we're not trying to replace titanium; we're trying to find applications where a stronger material would be useful," particularly because the material is still difficult to make. Still, he points to one particularly alluring quality: "you can use less of it because it's stronger."

The paper appears in the February 28 issue of the journal Nature. All experiments were performed in Caltech's Keck Laboratory of Engineering Materials. The other authors are material scientists Jin-Yoo Suh, Aaron Wiest, and Gang Duan, Caltech graduate students; Mary-Laura Lind, a visiting scientist; and Marios D. Demetriou, a senior research fellow. 

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Elisabeth Nadin
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New Technique Makes Tissues Transparent

PASADENA, Calif.-- If humans had see-through skin like a jellyfish, spotting disease like cancer would be a snap: Just look, and see a tumor form or grow.

But humans, of course, are not remotely diaphanous. "The reason a person is not transparent is that their tissues are highly scattering," sending light waves careening through the tissue instead of straight through, as they would through the tissue of that jellyfish, explains Changhuei Yang of the California Institute of Technology.

This scattering, in addition to rendering all of us opaque, makes the detection of disease a much trickier issue, requiring a host of diagnostic tests and procedures. But not, perhaps, for much longer, thanks to a new optical trick developed by Yang, an assistant professor of electrical engineering and bioengineering, and his colleagues, that counteracts the scattering of light and removes the distortion it creates in images.

A study describing the process appears in the February issue of the journal Nature Photonics.

It is well known that light scattering in a material is not exactly the random and unpredictable process one might imagine. In fact, scattering is deterministic, which means that the path that a beam of light takes as it traverses a particular slice of tissue and bounces and rebounds off of individual cells, is entirely predictable; if you again bounce light through that same swath of cells, it will scatter in exactly the same way.

The process is even reversible; if the individual photons of light that scattered through the tissue could be collected and sent back through the tissue, they'd bounce back along the same path and converge at the original spot from which they were sent. "The process is similar to the scattering of billiard balls on a pool table. If you can precisely reverse the paths and velocities of the billiard balls, you can cause the billiard balls to reassemble themselves into a rack," Yang explains.

Yang, along with his colleagues at Caltech, École Polytechnique Fédérale de Lausanne in Switzerland, and MIT, exploited this phenomenon to offset the murky nature of our tissues.

Their technique, called turbidity suppression by optical phase conjugation (TSOPC), is surprisingly simple. The scientists used a holographic crystal to record the scattered light pattern emerging from a 0.46-mm-thick piece of chicken breast. They then holographically played the pattern back through the tissue section to recover the original light beam. "This is similar to grabbing hold of the direction of time flow and turning it around; the time-reversed photons must retrace their trajectories through the tissue," Yang says. "The task is formidable though, as this is comparable to starting with a rack of 10 to the 18th power billiard balls (or photons), scattering them around the table, and attempting to reassemble them into a rack."

"Until we did this study, it wasn't clear that the effect will be observable with biological tissues. We were pleasantly surprised that the effect was readily observable and remarkably robust," Yang says. "This study opens up numerous possibilities in the use of optical time reversal in biomedicine."

One possible use of the technique is in photodynamic therapy, in which a highly focused beam of light is aimed at cancerous cells that have absorbed cell-killing light-sensitive compounds. When the light hits the cells, the compounds are activated and destroy the cells. Photodynamic therapy is most effective in treating cancers on the skin surface. Yang's technique, however, offers a way to concentrate light onto cancer-killing compounds located more deeply within tissue.

Yang's idea is to inject strongly light-scattering particles that are coated with light-activated cancer-killing drugs into diseased tissue. Shine a beam of light into the tissue, and it would be reflected off the scattering compounds as it bounces through the tissue. Some of the scattered light would return to the source, where it could be recorded as a hologram.

This hologram would contain information about the path that the scattered light took through the tissue, and, in effect, describe the optimal path BACK toward the light-scattering molecule--and the cancer-killing compounds. Playing back the signal with a stronger burst of light will then activate the therapeutic drugs, which kill the cancer cells.

In addition, the technique could offer a way to power miniature implants buried deep within tissues. "If you take a quick survey of what is out there at present, you will see that implants are fairly large," Yang says. "For example, a pacemaker is about the size of a cell phone. Why are they so big? A large part of the reason is because they need to carry their own power sources."

The key to making smaller implants, then--say, the size of a pen tip--is to eliminate the power sources. "I think implants that carry photovoltaic receivers are particularly promising," he says. "The effect can be applied to tailor light-delivery mechanisms to efficiently channel light into tissues and onto these implants."

Zahid Yaqoob, a postdoctoral fellow in electrical engineering at Caltech, performed most of the experiments reported in the paper. The other authors of the paper are Demetri Psaltis, professor of optics and dean of engineering, École Polytechnique Fédérale de Lausanne in Switzerland, and Michael S. Feld, a professor of physics at MIT. 

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Kathy Svitil
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Programming Biomolecular Self-Assembly Pathways

PASADENA, Calif.--Nature knows how to make proteins and nucleic acids (DNA and RNA) dance to assemble and sustain life. Inspired by this proof of principle, researchers at the California Institute of Technology have demonstrated that it is possible to program the pathways by which DNA strands self-assemble and disassemble, and hence to control the dynamic function of the molecules as they traverse these pathways.

The team invented a versatile DNA motif with three modular domains that can be made to interact with complementary domains in other species of the same motif. Rewiring these relationships changes the dynamic function of the system. To make it easier to design such systems, the researchers developed a graphical abstraction of the motif that can be used to write "molecular programs." As described in the January 17 issue of the journal Nature, the team experimentally demonstrated the execution of four such programs, each illustrating a different class of dynamic function.

The study was performed by a team of four at Caltech: Niles Pierce, associate professor of applied and computational mathematics and bioengineering; Peng Yin, senior postdoctoral scholar in bioengineering and computer science; Harry Choi, graduate student in bioengineering; and Colby Calvert, research technician.

Programming pathways is a bit like planning a road trip. The final destination might be important, but the true enjoyment is picking and traveling the route. In the test tube, the goal is not solely to direct the molecules to assemble into a target structure, but to engage them in a sequence of maneuvers so as to implement a prescribed dynamic function before the system reaches equilibrium. The energy to power the reactions is stored in the molecules themselves. Each molecule is initially trapped in a high-energy state so that it can release this energy as it engages in handshakes with other molecules.

A molecular program is written and executed in four steps. First, the intended assembly and disassembly pathways are described using a graphical abstraction called a "reaction graph." This molecular program is then translated into molecular mechanisms described at the level of base pairing between individual complementary bases. Computational design algorithms developed in the group are then used to encode this mechanism into the DNA sequences. Finally, the program is executed by mixing the physical molecules.

To demonstrate this approach, the team experimentally demonstrated a variety of dynamic functions: catalytic formation of branched junctions, cross-catalytic circuitry with exponential system kinetics, triggered dendritic growth of molecular "trees," and autonomous locomotion of a molecular bipedal walker.

As Pierce describes it, these results take them closer to achieving a long-term goal of creating a "compiler for biomolecular function"--an automated design tool that takes as input a molecular program and provides as output a set of biomolecules that execute the desired function. He remarks, "It's about time for the stone age of molecular compilers to begin." 

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Elisabeth Nadin
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Ortiz Wins Inaugural Prize in Solid Mechanics

PASADENA, Calif.--Michael Ortiz, the Hayman Professor of Aeronautics and Mechanical Engineering at the California Institute of Technology, is the first winner of the Rodney Hill Prize in Solid Mechanics. The newly established international prize, which will be awarded every four years, is also the first of its kind in this field.

The Hill Prize, sponsored by scientific publisher Elsevier Limited and awarded under the auspices of the International Union of Theoretical and Applied Mechanics, will be bestowed in August 2008 at the Union's 22nd Congress in Adelaide, Australia. Ortiz will receive a plaque and $25,000.

Ortiz is being recognized for several contributions within the past decade, among them a new method for computing plastic deformation. His Caltech colleague, mechanics and materials science professor Kaushik Bhattacharya, describes Ortiz's formulation as "a combination of the cutting edge of mechanics and the cutting edge of mathematics." Plastic deformation reshapes a material without breaking it, like stretching a piece of Silly Putty, in incremental steps. Ortiz developed the incremental variational principle, which allows the computation of plastic deformations as they proceed. "These processes immediately affect applications ranging from the most mundane engineering to the kind of sophisticated things that go into modern manufacturing," says Bhattacharya.

Another of Ortiz's contributions, which he calls the quasi-continuum method, was developed in collaboration with Rob Phillips, professor of applied physics and mechanical engineering at Caltech, while they were both at Brown University. The method forms a bridge between the way engineers describe mechanical properties of materials at the scale of the atom and the way they describe these properties at a larger scale.

Atomistic physics, at the scale of nanometers, applies quantum mechanics to the study of how energy interacts with matter. At the scale of micrometers, continuum mechanics treats an object's substance, or matter, as uniformly changing, and a different set of physical rules applies. The crux of the problem, says Bhattacharya, is that "the way we describe the physics at the atomistic scale is different from how we describe it at the continuum scale. But the properties you observe at the larger scale are the sum total of all the properties at every scale leading up to it. This formula unites the scales.

"The quasi-continuum method is the first rigorous way of approaching this problem," Bhattacharya notes. "Most approaches are ad hoc. This is a method that goes down to fundamental physics and mathematics to do it in a seamless manner. It has beautiful mathematics and physics in it and has a really fantastic computational structure. It was so far ahead of its time when they started doing this around 10 years ago. When you see it you say, 'That's exactly the way to do it!'"

Ortiz says he feels greatly honored to win the prize because of the recognition that it brings to theoretical and computational mechanics. "I have always enjoyed working closely with mathematicians, physicists, and chemists, and I hope that this prize will underscore the importance of those collaborations," he says. "I am greatly indebted to my brilliant students, who have been an inexhaustible source of energy and enthusiasm; to my colleagues and collaborators over the years, from whom I have learned most of what I know; and to my family for their constant and unconditional support."

According to Bhattacharya, the Hill Prize is intended to be the first highly and internationally visible prize for all of mechanics. Its analogue for fluid mechanics, the Batchelor Prize, was created at the same time and awarded to Caltech alumnus Howard Stone, the Joseph Professor of Engineering and Applied Mathematics at Harvard University.

About Ortiz's achievement Bhattacharya says, "I was not surprised that he won, because Michael is that caliber a person. He is extraordinarily creative. Every time you talk to him he has a new idea, and his ideas are really radical departures from what people have done in the field."

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Elisabeth Nadin
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Pulselike and Cracklike Ruptures in Earthquake Experiments

Lab experiments that mimic the way the ground moves during destructive earthquakes require some sophisticated equipment, and they yield valuable insights. Caltech scientists studying how sliding motion spreads along a fault interface conducted a series of experiments involving ultrafast digital cameras and high-speed laser velocimeters to replicate a range of realistic fault conditions.

The team documented for the first time a systematic variation in earthquake rupture patterns called pulselike and cracklike ruptures. The experiments also revealed that both types of ruptures can transition to a state known as supershear speed, which generates its own characteristic ground shaking. The results appeared in the November 27 issue of the journal Proceedings of the National Academy of Sciences.

The scientists include Xiao Lu, graduate student in aeronautics; Nadia Lapusta, assistant professor of mechanical engineering and geophysics; and Ares Rosakis, the von Kármán Professor of Aeronautics and Mechanical Engineering and director of the Graduate Aeronautical Laboratories.

Simple theoretical models of earthquake ruptures show they slide like a crack--the entire length of the fault slides for just about as long as the earthquake lasts. But slip models used by seismologists to match records of ground motions from past earthquakes have suggested a different mode of rupture, one that moves like a pulse. A pulse of slip would travel down the length of a fault like a ripple passing over the surface of a pond, with all motion contained in the ripple, and the fault surface "healing" in its wake.

The forces that build up on either side of a fault, known as tectonic loading, can vary greatly and lead to different types of fault slip behavior. "Numerical calculations of earthquake ruptures that use friction laws guided by laboratory experiments produce both crack- and pulselike modes, depending on how loaded the fault is," says Lapusta. "We set out to test the predictions of these calculations in our experimental study." Pulse modes are predicted by calculations where faults are less loaded, but to make a fault slip under these conditions, models have to assume that fault friction decreases as the fault slip gets faster. This behavior, called rate-weakening friction, has been of long-standing interest to Lapusta and to Thomas Heaton, professor of engineering seismology, whose influential work on slip pulses demonstrated their short duration, and who proposed rate-weakening friction as a likely explanation.

The experiments began with a 9.5-millimeter-thick photoelastic plate sliced at an angle through its length, simulating a fault in Earth's crust. Pressure on the two sides of the fault was applied incrementally at an angle to build up the different components of loading. To trigger an earthquake rupture, a nickel wire the diameter of a human hair was embedded in the plate interface and then electrically discharged, creating a small explosion followed by a spontaneously spreading rupture. Lasers measured the relative movements on each side of the fault after the shock, and a high-speed camera captured the movements in 5-microsecond intervals. The mini-explosions were repeated for various orientations of tectonic loading.

The experimental setup mimics conditions under which very large earthquakes rupture Earth's crust along major strike-slip faults like California's San Andreas fault or the Kunlun fault in northern Tibet. The initial experimental design was devised by Rosakis; Smits Professor of Geophysics, Emeritus Hiroo Kanamori; and their joint graduate student Kaiwen Xia, who is now a professor at the University of Toronto.

The new experimental results support the models that suggest faults can have pulselike ruptures. "This is the first time we observed this spontaneous pulselike rupture in an experiment that mimics crustal earthquakes. We proved its existence," says Lu.

The experiments also documented under what conditions pulselike ruptures arise. When the plate interface was oriented at a 70-degree angle to the direction of compression, the rupture propagated as a narrow pulse. At smaller angles, the pulses got wider, until they transitioned into cracklike sliding modes. These experimental observations demonstrate the role that tectonic loading plays in how earthquakes rupture, and imply that real faults are governed by rate-weakening friction.

Another experimental result is related to earthquake rupture speeds. Calculations since the 1970s have predicted phenomena known as supershear bursts, which would cause destructive, high-frequency ground motions. Rosakis, Kanamori, and Xia have demonstrated such bursts in their experiments in recent years. Supershear bursts were shown to have caused damage during the 1979 Imperial Valley, 1992 Landers, and 1999 Izmit, Turkey, earthquakes.

In the experiment by Lu, Lapusta, and Rosakis, supershear propagation is seen to arise during both pulselike and cracklike earthquake ruptures. "That's new--nobody has seen before that either of those modes could transition to supershear," says Rosakis. Shock waves generated by supershear propagation generate more ground shaking, he adds, and notes that with more details about exactly how earthquakes rupture, scientists can devise more sophisticated ways for buildings to survive the specific types of shaking that arise.

Writer: 
Elisabeth Nadin
Writer: 

Genetic Underpinnings of Wood Digestion by Termite Gut Microbes Revealed

PASADENA, Calif.--When termites are chewing on your home, your immediate thought probably isn't "I wonder how they digest that stuff?" But biologists have been gnawing on the question for more than a century. The key is not just the termite, but what lives in its gut. A multitude of genes from the microbes populating the hindgut of a termite have been sequenced and analyzed, and the findings reported today in the journal Nature.

California Institute of Technology associate professor of environmental microbiology Jared Leadbetter led a team of researchers from other universities, private industry, and the Department of Energy (DOE) in uncovering the genetic underpinnings and the roles of bacteria in wood digestion by "higher termites." These insects abound in tropical and subtropical ecosystems. What the team found, says Leadbetter, is "a comprehensive set of blueprints for the bacteria that help dismantle wood."

Prior to this study, only one gene--in the insect itself--had been connected to the termite's rare ability to digest and nourish itself with wood, a substance that is energy-rich but hard to break down. It had also long been suspected that the 250 bacterial species that crowd the pinhead volume of a higher termite's hindgut might be directly involved in the process. But there was no way of knowing their roles for sure, because most of the organisms die quickly when removed from their host. Although the first bacterium genome was sequenced in 1994, it was a few years before scientists even considered sequencing entire communities of multiple species of organisms.

Leadbetter and his colleagues proposed to the DOE Joint Genome Institute (JGI) that the gut community of the Costa Rican termite Nasutitermes be examined because it is abundant and it plays significant roles in the wood degradation that helps to renew ecosystems. Leadbetter joined forces with collaborators at JGI, Verenium Corporation's San Diego facilities, and INBio, the National Biodiversity Institute of Costa Rica. They sequenced and analyzed more than 80,000 genes encoded by many of the hindgut bacteria species. "This was a fairly risky project when we proposed it," says Leadbetter, because "in these abundant tropical termites, there was no compelling evidence that these microbes play direct roles in cellulose degradation."

When the results started coming in, "we all breathed a big sigh of relief, because it turned out to be a gold mine in there," Leadbetter says. They found nearly 1,000 genes that underlie roles in breaking down two of wood's main components, cellulose and xylan, into their component sugars. The degradation of cellulose and xylan requires an arsenal of enzymes because of the huge diversity of biochemical bonds in wood. "This isn't some soft paper or grass we're talking about," says Leadbetter. "It's a hard substrate." Wood is made of three tightly intertwined compounds; taking it apart is a challenge, and termites are among the few known animals that can do it.

Leadbetter and his colleagues hope to eventually uncover exactly how each gene is involved in degrading wood, and where the energy the termite derives from the wood goes. This has recently become a focus of interest for those interested in developing an effective, industrial method to convert wood into ethanol. The challenge lies in events at the start of the process, like those involved in breaking down cellulose and xylan. Leadbetter and his colleagues believe that by investigating the genes that underlie these primary reactions, better ways of manufacturing biofuel can eventually be developed.

The study also identified nearly 100 different species of bacteria called spirochetes that belong to the genus Treponema. This membership makes them closely related to the bacterium that causes syphilis and to other spirochetes implicated in Lyme disease and gum disease. In termites, though, the findings show that these spirochetes actually benefit the health of their hosts. The genome sequencing also showed that the spirochetes are active in processes that generate hydrogen, an energy-rich gas, from wood. Certain genes also indicate that gut spirochetes can essentially taste or smell hydrogen and will swim either to or from its sources in the gut. In general, Leadbetter says, it looks like "these bacteria differ from those that dominate the gut tracts of humans and other mammals in their broad capacity to swim in response to diverse chemical stimuli. This behavior may be relevant to effective wood degradation."

Other Caltech authors of the paper are Eric Matson, a postdoctoral scholar in environmental science and engineering; Xinning Zhang, a graduate student in environmental science and engineering; and Elizabeth Ottesen, a graduate student in biology. Group leaders are Dan Robertson of Verenium Corporation, Phil Hugenholtz of the JGI, Giselle Tamayo of INBio, and Eric Mathur, formerly of Diversa (now at Synthetic Genomics).

Writer: 
Elisabeth Nadin
Writer: 

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