Caltech Senior Wins Churchill Scholarship

Caltech senior Andrew Meng has been selected to receive a Churchill Scholarship, which will fund his graduate studies at the University of Cambridge for the next academic year. Meng, a chemistry and physics major, was one of only 14 students nationwide who were chosen to receive the fellowship this year.

Taking full advantage of Caltech's strong tradition of undergraduate research, Meng has worked since his freshman year in the lab of Nate Lewis, the George L. Argyros Professor and professor of chemistry. Over the course of three Summer Undergraduate Research Fellowships (SURFs) and several terms in the lab, Meng has investigated various applications of silicon microwire solar cells. Lewis's group has shown that arrays of these ultrathin wires hold promise as a cost-effective way to construct solar cells that can convert light into electricity with relatively high efficiencies.

Meng, who grew up in Baton Rouge, Louisiana, first studied some of the fundamental limitations of silicon microwires in fuel-forming reactions. In these applications, it is believed that the microwires can harness energy from the sun to drive chemical reactions such as the production of hydrogen and oxygen from splitting water. Meng's work showed that the geometry of the microwires would not limit the fuel-forming reaction as some had expected.

More recently, Meng has turned his attention to using silicon microwires to generate electricity. He is developing an inexpensive electrical contact to silicon microwire chips, using a method that facilitates scale-up and can be applied to flexible solar cells.

"Andrew is one of the best undergraduates that I have had the pleasure of working with in over a decade," says Lewis. "He excels in academics, in leadership, and in research. I believe he is truly worthy of the distinction of receiving a Churchill Fellowship. " 

As he pursues a Master of Philosophy degree in chemistry at the University of Cambridge over the next year, Meng will work in the group of theoretical chemist Michiel Sprik. He plans to apply computational methods to his studies of fuel-forming reactions using solar-energy materials.

"I'm very grateful for this opportunity to learn a computational perspective, since up until now I've been doing experimental work," Meng says. "I'm very excited, and most importantly, I'd like to thank Caltech and all of my mentors and co-mentors, without whom I would not be in this position today."

According to the Winston Churchill Foundation's website, the Churchill Scholarship program "offers American citizens of exceptional ability and outstanding achievement the opportunity to pursue graduate studies in engineering, mathematics, or the sciences at Cambridge. One of the newer colleges at the University of Cambridge, Churchill College was built as the national and Commonwealth tribute to Sir Winston, who in the years after the Second World War presciently recognized the growing importance of science and technology for prosperity and security. Churchill College focuses on the sciences, engineering, and mathematics." The first Churchill Scholarships were awarded in 1963, and this year's recipients bring the total to 479 Churchill Scholars.

Each year, a select group of universities, including Caltech, is eligible to nominate students for consideration for the scholarship. Meng is the seventh Caltech student to have won the award since the year 2000. A group of Caltech faculty members and researchers work with Lauren Stolper, director of fellowships advising, to identify and nominate candidates. This year, the members of the group were Churchill Scholar alumni John Brady, the Chevron Professor of Chemical Engineering and professor of mechanical engineering; Mitchio Okumura, professor of chemical physics; Alan Cummings, senior research scientist; and Eric Rains, professor of mathematics.

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Arnold Awarded National Medal of Technology and Innovation

Frances H. Arnold, a leader in the field of protein engineering and a member of the faculty at Caltech, was one of 11 inventors to be awarded the 2011 National Medal of Technology and Innovation. President Barack Obama presented Arnold with the medal on February 1 in a ceremony in the East Room of the White House.

Watch the video from the event.

 
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Jorgensen Laboratory Awarded LEED Platinum Certification

The recent renovations of the Jorgensen Laboratory included many upgrades that were designed to reflect Caltech's commitment to sustainability. Now the building has achieved LEED Platinum certification, the highest honor of the U.S. Green Building Council.

"Achieving Platinum certification on this building was particularly rewarding given the fact that the building will serve as a studio for sustainable energy research," says John Onderdonk, director of sustainability programs at Caltech.

LEED—Leadership in Energy and Environmental Design—is a voluntary program that provides verification of green building design through a survey of prerequisites and guideline credits. To obtain LEED certification, a building must earn a minimum of 40 points on a 110-point LEED rating system scale. Jorgensen received 87 points—80 is the minimum needed for Platinum certification—for its conservation features, which include a "green" roof, natural ventilation systems, use of on-campus solar photovoltaic power, and low-flow water fixtures, among other environmentally conscious details.

Jorgensen is one of 20 LEED Platinum-certified higher-education lab buildings in the country, and one of seven in the state. It is the second higher-education lab building in the state to receive LEED Platinum certification under the current rating system. Caltech's renovation of the Linde + Robinson Lab also received LEED Platinum status last year.

The Jorgensen Lab officially opened in October 2012 and houses scientists who are focused on clean-energy research

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Friday, January 25, 2013
Annenberg 121

Course Ombudspeople Lunch

TEDxCaltech: Surmounting the Blood-Brain Barrier

This week we will be highlighting the student speakers who auditioned and were selected to give five-minute talks about their brain-related research at TEDxCaltech: The Brain, a special event that will take place on Friday, January 18, in Beckman Auditorium. 

In the spirit of ideas worth spreading, TED has created a program of local, self-organized events called TEDx. Speakers are asked to give the talk of their lives. Live video coverage of the TEDxCaltech experience will be available during the event at http://tedxcaltech.caltech.edu.

The brain needs its surroundings to be just right. That is, unlike some internal organs, such as the liver, which can process just about anything that comes its way, the brain needs to be protected and to have a chemical environment with the right balance of proteins, sugars, salts, and other metabolites. 

That fact stood out to Caltech MD/PhD candidate and TEDxCaltech speaker Devin Wiley when he was studying medicine at the Keck School of Medicine of USC. "In certain cases, one bacterium detected in the brain can be a medical emergency," he says. "So the microenvironment needs to be highly protected and regulated for the brain to function correctly."

Fortunately, a semipermeable divide, known as the blood-brain barrier, is very good at maintaining such an environment for the brain. This barricade—made up of tightly packed blood-vessel cells—is effective at precisely controlling which molecules get into and out of the brain. Because the blood-brain barrier regulates the molecular traffic into the brain, it presents a significant challenge for anyone wanting to deliver therapeutics to the brain. 

At Caltech, Wiley has been working with his advisor, Mark Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering, to develop a work-around—a way to sneak therapeutics past the barrier and into the brain to potentially treat neurologic diseases such as Alzheimer's and Parkinson's. The scientists' strategy is to deliver large-molecule therapeutics (which are being developed by the Davis lab as well as other research groups) tucked inside nanoparticles that have proteins attached to their surface. These proteins will bind specifically to receptors on the blood-brain barrier, allowing the nanoparticles and their therapeutic cargo to be shuttled across the barrier and released into the brain.

"In essence, this is like a Trojan horse," Wiley explains. "You're tricking the blood-brain barrier into transporting drugs to the brain that normally wouldn't get in."

During his five-minute TEDxCaltech talk on Friday, January 18, Wiley will describe this approach and his efforts to design nanoparticles that can transport and release therapeutics into the brain.

For Wiley, the issue of delivering therapeutics to the brain is more than a fascinating research problem. His grandmother recently passed away from Alzheimer's disease, and his wife's grandmother also suffers from the neurodegenerative disorder.

"This is something that affects a lot of people," Wiley says. "Treatments for cardiovascular diseases, cancer, and infectious diseases are really improving. However, better treatments for brain diseases are not being discovered as quickly. So what are the issues? I want to tell the story of one of them."

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Caltech Chemical Engineer Frances Arnold Awarded National Medal of Technology and Innovation

PASADENA, Calif.—Frances H. Arnold, a leader in the field of protein engineering and a member of the faculty at the California Institute of Technology (Caltech) has been named one of 11 inventors who are the recipients of the 2011 National Medal of Technology and Innovation. The announcement was made by the White House on December 21.

Arnold, who is the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering, and Biochemistry at Caltech, pioneered methods of "directed evolution" that are now widely used to create biological catalysts for use in industrial processes, including the production of fuels and chemicals from renewable resources. In a process akin to breeding by artificial selection, directed evolution uses mutation and screening to optimize the amino-acid sequence of a protein and give it new capabilities or improve its performance. 

Arnold says her work is strongly motivated by a desire to find ways to produce fuels that can help lower carbon dioxide emissions. "I would like my children to grow up in a world that is even better than the one that I grew up in," she says. "For that to happen, we have to stop wasting precious resources and learn to live in a sustainable fashion. Biology can and should be one of the solutions."

Arnold's award brings to 13 the number of Caltech faculty members, alumni, and trustees who have received the National Medal of Technology and Innovation.

"Professor Arnold's work has led to a radical transformation in the way people understand protein engineering and what it can accomplish," says Caltech president Jean-Lou Chameau. "We are very proud of all that Professor Arnold has achieved and celebrate this recognition of her contributions." 

The National Medal of Technology and Innovation was established by Congress in 1980, and complements the older National Medal of Science. The U.S. Department of Commerce's Patent and Trademark Office administers the medal on behalf of the White House.

The White House also announced the winners of the 2011 National Medal of Science. A Caltech alumnus and former chair of the Division of Biology, Leroy Hood, was among the 12 awardees. His citation brings the number of Caltech faculty members and alumni to have received the National Medal of Science to 57.

"I am proud to honor these inspiring American innovators," said President Barack Obama in the press release. "They represent the ingenuity and imagination that has made this Nation great—and they remind us of the enormous impact a few good ideas can have when these creative qualities are unleashed in an entrepreneurial environment."

Arnold says her discoveries and accomplishments were made possible by her position at Caltech, whose structure encourages work that crosses traditional disciplinary boundaries. Indeed, her work spans chemistry, bioengineering, biochemistry, molecular biology, microbiology, and chemical engineering.

She also thanks her colleagues and students. "I'm thrilled because this is a recognition not just of my work, but of the work of many people around the world who have developed and applied these methods," Arnold says. "I've also been privileged to work with a brilliant and enthusiastic group of young people over the years."

Arnold received her undergraduate degree in mechanical and aerospace engineering at Princeton University in 1979. She became interested in protein engineering during graduate school at UC Berkeley at the beginning of the biotechnology revolution, when she realized that the then-new methods of genetic engineering offered a path to solving pressing human problems using biology.

"It was clear that being able to rewrite the code of life signified a future full of fantastic technological possibilities," she says. "I wanted to be on board."

Arnold received her PhD in 1985 and arrived at Caltech as a visiting associate in 1986. She joined the faculty as an assistant professor the following year and became associate professor in 1992, professor in 1996, and Dickinson Professor in 2000. She has been honored with many awards, including the 2011 Charles Stark Draper Prize, and holds the rare distinction of having been elected to all three branches of the National Academies—the National Academy of Engineering (2000), the Institute of Medicine (2004), and the National Academy of Sciences (2008).

"Frances has made critically important contributions through her development of directed evolution," says Jacqueline Barton, chair of the Division of Chemistry and Chemical Engineering at Caltech. "It is outstanding that this work is being recognized through the National Medal."

Arnold and her fellow medal recipients will receive their awards at a White House ceremony in early 2013. 

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Unlocking New Talents in Nature

Caltech protein engineers create new biocatalysts

PASADENA, Calif.—Protein engineers at the California Institute of Technology (Caltech) have tapped into a hidden talent of one of nature's most versatile catalysts. The enzyme cytochrome P450 is nature's premier oxidation catalyst—a protein that typically promotes reactions that add oxygen atoms to other chemicals. Now the Caltech researchers have engineered new versions of the enzyme, unlocking its ability to drive a completely different and synthetically useful reaction that does not take place in nature. 

The new biocatalysts can be used to make natural products—such as hormones, pheromones, and insecticides—as well as pharmaceutical drugs, like antibiotics, in a "greener" way.

"Using the power of protein engineering and evolution, we can convince enzymes to take what they do poorly and do it really well," says Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry at Caltech and principal investigator on a paper about the enzymes that appears online in Science. "Here, we've asked a natural enzyme to catalyze a reaction that had been devised by chemists but that nature could never do."

Arnold's lab has been working for years with a bacterial cytochrome P450. In nature, enzymes in this family insert oxygen into a variety of molecules that contain either a carbon-carbon double bond or a carbon-hydrogen single bond. Most of these insertions require the formation of a highly reactive intermediate called an oxene.

Arnold and her colleagues Pedro Coelho and Eric Brustad noted that this reaction has a lot in common with another reaction that synthetic chemists came up with to create products that incorporate a cyclopropane—a chemical group containing three carbon atoms arranged in a triangle. Cyclopropanes are a necessary part of many natural-product intermediates and pharmaceuticals, but nature forms them through a complicated series of steps that no chemist would want to replicate.

"Nature has a limited chemical repertoire," Brustad says. "But as chemists, we can create conditions and use reagents and substrates that are not available to the biological world."

The cyclopropanation reaction that the synthetic chemists came up with inserts carbon using intermediates called carbenes, which have an electronic structure similar to oxenes. This reaction provides a direct route to the formation of diverse cyclopropane-containing products that would not be accessible by natural pathways. However, even this reaction is not a perfect solution because some of the solvents needed to run the reaction are toxic, and it is typically driven by catalysts based on expensive transition metals, such as copper and rhodium. Furthermore, tweaking these catalysts to predictably make specific products remains a significant challenge—one the researchers hoped nature could overcome with evolution's help.

Given the similarities between the two reaction systems—cytochrome P450's natural oxidation reactions and the synthetic chemists' cyclopropanation reaction— Arnold and her colleagues argued that it might be possible to convince the bacterial cytochrome P450 to create cyclopropane-bearing compounds through this more direct route.  Their experiments showed that the natural enzyme (cytochrome P450) could in fact catalyze the reaction, but only very poorly; it generated a low yield of products, didn't make the specific mix of products desired, and catalyzed the reaction only a few times. In comparison, transition-metal catalysts can be used hundreds of times. 

That's where protein engineering came in. Over the years, Arnold's lab has created thousands of cytochrome P450 variants by mutating the enzyme's natural sequence of amino acids, using a process called directed evolution. The researchers tested variants from their collections to see how well they catalyzed the cyclopropane-forming reaction. A handful ended up being hits, driving the reaction hundreds of times. 

Being able to catalyze a reaction is a crucial first step, but for a chemical process to be truly useful it has to generate high yields of specific products. Many chemical compounds exist in more than one form, so although the chemical formulas of various products may be identical, they might, for example, be mirror images of each other or have slightly different bonding structures, leading to dissimilar behavior. Therefore, being able to control what forms are produced and in what ratio—a quality called selectivity—is especially important.

Controlling selectivity is difficult. It is something that chemists struggle to do, while nature excels at it. That was another reason Arnold and her team wanted to investigate cytochrome P450's ability to catalyze the reaction.

"We should be able to marry the impressive repertoire of catalysts that chemists have invented with the power of nature to do highly selective chemistry under green conditions," Arnold says.

So the researchers further "evolved" enzyme variants that had worked well in the cyclopropanation reaction, to come up with a spectrum of new enzymes. And those enzymes worked—they were able to drive the reaction many times and produced many of the selectivities a chemist could desire for various substrates.  

Coelho says this work highlights the utility of synthetic chemistry in expanding nature's catalytic potential. "This field is still in its infancy," he says. "There are many more reactions out there waiting to be installed in the biological world."

The paper, "Olefin cyclopropanation via carbene insertion catalyzed by engineered cytochrome P450 enzymes," was also coauthored by Arvind Kannan, now a Churchill Scholar at Cambridge University; Brustad is now an assistant professor at the University of North Carolina at Chapel Hill. The work was supported by a grant from the U.S. Department of Energy and startup funds from UNC Chapel Hill.

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Credit: Benjamin Deverman/Caltech

Gene therapy for boosting nerve-cell repair

Caltech scientists have developed a gene therapy that helps the brain replace its nerve-cell-protecting myelin sheaths—and the cells that produce those sheaths—when they are destroyed by diseases like multiple sclerosis and by spinal-cord injuries. Myelin ensures that nerve cells can send signals quickly and efficiently.

Credit: L. Moser and P. M. Bellan, Caltech

Understanding solar flares

By studying jets of plasma in the lab, Caltech researchers discovered a surprising phenomenon that may be important for understanding how solar flares occur and for developing nuclear fusion as an energy source. Solar flares are bursts of energy from the sun that launch chunks of plasma that can damage orbiting satellites and cause the northern and southern lights on Earth.

Coincidence—or physics?

Caltech planetary scientists provided a new explanation for why the "man in the moon" faces Earth. Their research indicates that the "man"—an illusion caused by dark-colored volcanic plains—faces us because of the rate at which the moon's spin rate slowed before becoming locked in its current orientation, even though the odds favored the moon's other, more mountainous side.

Choking when the stakes are high

In studying brain activity and behavior, Caltech biologists and social scientists learned that the more someone is afraid of loss, the worse they will perform on a given task—and that, the more loss-averse they are, the more likely it is that their performance will peak at a level far below their actual capacity.

Credit: NASA/JPL-Caltech

Eyeing the X-ray universe

NASA's NuSTAR telescope, a Caltech-led and -designed mission to explore the high-energy X-ray universe and to uncover the secrets of black holes, of remnants of dead stars, of energetic cosmic explosions, and even of the sun, was launched on June 13. The instrument is the most powerful high-energy X-ray telescope ever developed and will produce images that are 10 times sharper than any that have been taken before at these energies.

Credit: CERN

Uncovering the Higgs Boson

This summer's likely discovery of the long-sought and highly elusive Higgs boson, the fundamental particle that is thought to endow elementary particles with mass, was made possible in part by contributions from a large contingent of Caltech researchers. They have worked on this problem with colleagues around the globe for decades, building experiments, designing detectors to measure particles ever more precisely, and inventing communication systems and data storage and transfer networks to share information among thousands of physicists worldwide.

Credit: Peter Day

Amplifying research

Researchers at Caltech and NASA's Jet Propulsion Laboratory developed a new kind of amplifier that can be used for everything from exploring the cosmos to examining the quantum world. This new device operates at a frequency range more than 10 times wider than that of other similar kinds of devices, can amplify strong signals without distortion, and introduces the lowest amount of unavoidable noise.

Swims like a jellyfish

Caltech bioengineers partnered with researchers at Harvard University to build a freely moving artificial jellyfish from scratch. The researchers fashioned the jellyfish from silicon and muscle cells into what they've dubbed Medusoid; in the lab, the scientists were able to replicate some of the jellyfish's key mechanical functions, such as swimming and creating feeding currents. The work will help improve researchers' understanding of tissues and how they work, and may inform future efforts in tissue engineering and the design of pumps for the human heart.

Credit: NASA/JPL-Caltech

Touchdown confirmed

After more than eight years of planning, about 354 million miles of space travel, and seven minutes of terror, NASA's Mars Science Laboratory successfully landed on the Red Planet on August 5. The roving analytical laboratory, named Curiosity, is now using its 10 scientific instruments and 17 cameras to search Mars for environments that either were once—or are now—habitable.

Credit: Caltech/Michael Hoffmann

Powering toilets for the developing world

Caltech engineers built a solar-powered toilet that can safely dispose of human waste for just five cents per use per day. The toilet design, which won the Bill and Melinda Gates Foundation's Reinventing the Toilet Challenge, uses the sun to power a reactor that breaks down water and human waste into fertilizer and hydrogen. The hydrogen can be stored as energy in hydrogen fuel cells.

Credit: Caltech / Scott Kelberg and Michael Roukes

Weighing molecules

A Caltech-led team of physicists created the first-ever mechanical device that can measure the mass of an individual molecule. The tool could eventually help doctors to diagnose diseases, and will enable scientists to study viruses, examine the molecular machinery of cells, and better measure nanoparticles and air pollution.

Splitting water

This year, two separate Caltech research groups made key advances in the quest to extract hydrogen from water for energy use. In June, a team of chemical engineers devised a nontoxic, noncorrosive way to split water molecules at relatively low temperatures; this method may prove useful in the application of waste heat to hydrogen production. Then, in September, a group of Caltech chemists identified the mechanism by which some water-splitting catalysts work; their findings should light the way toward the development of cheaper and better catalysts.

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In 2012, Caltech faculty and students pursued research into just about every aspect of our world and beyond—from understanding human behavior, to exploring other planets, to developing sustainable waste solutions for the developing world.

In other words, 2012 was another year of discovery at Caltech. Here are a dozen research stories, which were among the most widely read and shared articles from Caltech.edu.

Did we skip your favorite? Connect with Caltech on Facebook to share your pick.

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Theodor Agapie Wins American Chemical Society Award

Theodor Agapie, assistant professor of chemistry at Caltech, has received the 2013 Award in Pure Chemistry from the American Chemical Society (ACS). The award will be presented at the national meeting of the ACS in New Orleans in April.

ACS is recognizing Agapie for his laboratory research on inorganic compounds. According to Agapie, his lab is working toward developing catalysts for artificial photosynthesis, a promising area of research into sustainable energy.

"I am very honored and thrilled to have received this award, particularly because I think it provides recognition for the efforts of my entire research team," says Agapie. "I have been lucky to work with a group of very talented young scientists who made the discoveries noted in this award."

Agapie, a native of Romania, received his bachelor's degree from MIT in 2001 and his PhD from Caltech in 2007. He has been an assistant professor at Caltech since early 2009. Since joining Caltech's faculty, Agapie has been named a Searle Scholar, a Sloan Research Fellow, and the recipient of a National Science Foundation CAREER Award. The Award in Pure Chemistry comes with a $5,000 prize and travel expenses for the upcoming national meeting of the American Chemical Society.

 

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Tuesday, April 9, 2013
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