Caltech Names Six Distinguished Alumni

Caltech has announced that Eric Betzig (BS '83), Janet C. Campagna (MS '85), Neil Gehrels (PhD '82), Carl V. Larson (BS '52), Thomas J. "Tim" Litle IV (BS '62), and Ellen D. Williams (PhD '82) are this year's recipients of the Distinguished Alumni Award.

First presented in 1966, the award is the highest honor the Institute bestows upon its graduates. It is awarded in recognition of a particular achievement of noteworthy value, a series of such achievements, or a career of noteworthy accomplishment. Presentation of the awards will be given on Saturday, May 21, 2016, as part of Caltech's Seminar Day.

The 2016 Distinguished Alumni Award recipients are

Eric Betzig (BS '83, Physics)

Physicist; Group Leader, Janelia Research Campus, Howard Hughes Medical Institute

Betzig is being recognized for his groundbreaking contributions to microscopy. He pioneered a method known as single-molecule microscopy, or "nanoscopy," which allows cellular structures at the nanoscale to be observed using optical microscopy. For the work, he shared the Nobel Prize in Chemistry in 2014.

Janet C. Campagna (MS '85, Social Science)

CEO, QS Investors

Campagna is being recognized for her contributions to quantitative investment and for her leadership in the financial industry. Campagna is the founder of QS Investors, LLC, a leading customized solutions and global quantitative equities provider. She is responsible for all business, strategic, and investment decisions within QS Investors. 

Neil Gehrels (PhD '82, Physics)

Chief of the Astroparticle Physics Laboratory, NASA's Goddard Space Flight Center

Gehrels is being recognized for his scientific leadership in the study of gamma ray bursts as well as for his significant contributions to high-energy astrophysics, infrared astronomy, and instrument development.

Carl V. Larson (BS '52, Mechanical Engineering)

Larson is being recognized for his accomplished career in the electronics industry. Over the course of three decades, Larson has held numerous and diverse leadership roles in fields ranging from engineering to marketing. He is also being celebrated for his sustained commitment to the research, students, and alumni of Caltech.

Thomas J. "Tim" Litle IV  (BS '62, Engineering and Applied Science)

Founder and Chairman, Litle & Co.

Litle is being recognized for his revolutionary contributions to commerce. Through innovations such as the presorted mail program he developed for the U.S. Postal Service and the three-digit security codes on credit cards, Litle has made global business more efficient and secure.

Ellen D. Williams (PhD '82, Chemistry)

Director, Advanced Research Projects Agency-Energy (ARPA-E)

Williams is being recognized for her sustained record of innovation and achievement in the area of structural surface physics. She founded the Materials Research Science and Engineering Center at the University of Maryland and was the chief scientist for BP. She now serves as director of the Advanced Research Project Agency (ARPA-E) in the U.S. Department of Energy.

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The awardees range from the class of 1952 to the class of 1983, across a wide range of divisions.

Counting Molecules with an Ordinary Cell Phone

Diagnostic health care is often restricted in areas with limited resources, because the procedures required to detect many of the molecular markers that can diagnose diseases are too complex or expensive to be used outside of a central laboratory. Researchers in the lab of Rustem Ismagilov, Caltech's Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering and director of the Jacobs Institute for Molecular Engineering for Medicine, are inventing new technologies to help bring emerging diagnostic capabilities out of laboratories and to the point of care. Among the important requirements for such diagnostic devices is that the results—or readouts—be robust against a variety of environmental conditions and user errors.

To address the need for a robust readout system for quantitative diagnostics, researchers in the Ismagilov lab have invented a new visual readout method that uses analytical chemistries and image processing to provide unambiguous quantification of single nucleic-acid molecules that can be performed by any cell-phone camera.

The visual readout method is described and validated using RNA from the hepatitis C virus—HCV RNA—in a paper in the February 22 issue of the journal ACS Nano.

The work utilizes a microfluidic technology called SlipChip, which was invented in the Ismagilov lab several years ago. A SlipChip serves as a portable lab-on-a-chip and can be used to quantify concentrations of single molecules. Each SlipChip encodes a complex program for isolating single molecules (such as DNA or RNA) along with chemical reactants in nanoliter-sized wells. The program also controls the complex reactions in each well: the chip consists of two plates that move—or "slip"—relative to one another, with each "slip" joining or separating the hundreds or even thousands of tiny wells, either bringing reactants and molecules into contact or isolating them. The architecture of the chip enables the user to have complete control over these chemical reactions and can prevent contamination, making it an ideal platform for a user-friendly, robust diagnostic device.

The new visual readout method builds upon this SlipChip platform. Special indicator chemistries are integrated into the wells of the SlipChip device. After an amplification reaction—a reaction that multiplies nucleic-acid molecules—wells change color depending on whether the reaction in it was positive or negative. For example, if a SlipChip is being used to count HCV RNA molecules in a sample, a well containing an RNA molecule that amplified during the reaction would turn blue; whereas a well lacking an RNA molecule would remain purple.

To read the result, a user simply takes a picture of the entire SlipChip using any camera phone. Then the photo is processed using a ratiometric approach that transforms the colors detected by the camera's sensor into an unambiguous readout of positives and negatives.

Previous SlipChip technologies utilized a chemical that would fluoresce when a reaction took place within a well. But those readouts can be too subtle for detection by a common cell-phone camera or can require specific lighting conditions. The new method provides guidelines for selecting indicators that yield color changes compatible with the color sensitivities of phone cameras, and the ratiometric processing removes the need for a user to distinguish colors by sight.

"The readout process we developed can be used with any cell-phone camera," says Jesus Rodriguez-Manzano, a postdoctoral scholar in chemical engineering and one of two first authors on the paper. "It is rapid, automated, and doesn't require counting or visual interpretation, so the results can be read by anyone—even users who are color blind or working under poor lighting conditions. This robustness makes our visual readout method appropriate for integration with devices used in any setting, including at the point of care in limited-resource settings. This is critical because the need for highly sensitive diagnostics is greatest in such regions."

The paper is titled "Reading Out Single-Molecule Digital RNA and DNA Isothermal Amplification in Nanoliter Volumes with Unmodified Camera Phones." In addition to Rodriguez-Manzano, Mikhail Karymov is also a first author. Other Caltech coauthors include Stefano Begolo, David Selck, Dmitriy Zhukov, and Erik Jue. The work was funded by grants from the Defense Advanced Research Projects Agency, the National Institutes of Health, and an Innovation in Regulatory Science Award from the Burroughs Wellcome Fund. Microfluidic technologies developed by Ismagilov's group have been licensed to Emerald BioStructures, RainDance Technologies, and SlipChip Corp., of which Ismagilov is a founder.

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The new visual readout method to count individual nucleic-acid molecules within a sample can be performed by any cell-phone camera.
Monday, February 29, 2016

Modeling molecules at the microscale

Considering the Future

Science and Society conference to honor Nobel Laureate Ahmed Zewail

Can we find life on other planets? Can we bridge the economic divide between rich and poor? Can we engineer the human body to live longer than our genes currently allow, and should we even attempt such a thing?

On February 26, some of the nation's leading scientists and researchers—including five Nobel laureates, two of whom are from Caltech—will gather at Caltech to discuss some of the most perplexing questions facing humanity. During a one-day conference titled "Science and Society," they will address an eclectic mix of topics ranging from current efforts to reduce global poverty to the mechanical workings of clocks so accurate that they lose less than a second every 300 million years.

The conference has been organized in honor of Ahmed Zewail, Caltech's Linus Pauling Professor of Chemistry and professor of physics, who was the sole recipient of the 1999 Nobel Prize in Chemistry for his development of the field of femtochemistry. Zewail, who also serves as director of Caltech's Physical Biology Center for Ultrafast Science and Technology, has lived the concept that science should drive the betterment of society, not only in his academic life, but in his advocacy as a U.S. science envoy to the Middle East and scientific advisor to the United Nations, and as a leader within his native Egypt, as exemplified by the role he played both during and after the Egyptian revolution of 2011.

"Science plays a vital role in helping people live better lives and helping humanity understand its place in the universe, and it's a rare treat for so many distinguished people to gather in one place to discuss these fascinating topics," says Zewail. "The theme that will shine through in this conference is that a passion for science, combined with a sense of optimism, can make the almost-impossible possible."

The conference, which will be held in Beckman Auditorium, will include speakers from Caltech, Stanford, the University of Maryland, and the Jet Propulsion Laboratory. Caltech's president, Thomas F. Rosenbaum, and provost, Edward Stolper, as well as Jacqueline Barton, chair of the Division of Chemistry and Chemical Engineering, and Fiona Harrison, the Kent and Joyce Kresa Leadership Chair of the Division of Physics, Mathematics and Astronomy, will open the conference; Rosenbaum will also provide concluding remarks at the end of the day.

The other speakers will include Caltech Nobel laureate David Baltimore, who will talk about "The Future of Medicine" and the CRISPR technology that is now teaching scientists how to "edit" a person's genes, an undertaking that raises a host of ethical questions. "Since medicine has brought us from a life expectancy of 45 years to one of 77 in the last century, it is reasonable to expect medicine will be able to extend it to 85 or even 100," says Baltimore, the Robert Andrews Millikan Professor of Biology. "But to go much beyond that, we would need to think about altering our genes. Should we think about that?"

William Phillips, a physicist at the National Institute of Standards and Technology and a Nobel laureate, will give a talk titled "Time, Einstein, and the Coolest Stuff in the Universe." His discussion will focus on how scientists are using supercold atoms to "allow tests of some of Einstein's strangest predictions" and to create supremely accurate atomic clocks, which, he says, "are essential to industry, commerce, and science." Phillips is also a Distinguished University Professor at the University of Maryland, College Park.

JPL director Charles Elachi will predict—in his talk about "The Future of Space Exploration"—that, during the next decade, we will establish permanent scientific stations on Mars and engage in a search for present or past ocean life on the moons of Europa, Enceladus, and Titan. Elachi believes that, in the near future, "we will also be imaging and characterizing planets around neighboring stars to see if we are alone."

Roger Kornberg, Nobel laureate and the Mrs. George A. Winzer Professor in Medicine at the Stanford School of Medicine, will discuss "The End of Disease." His talk will look at the challenges faced by the scientific community from both "biomedical and political myopia," while also considering the capacity and power of physics, chemistry, and biology to bring modern medicine forward.

A. Michael Spence, a Nobel laureate from the Stanford Graduate School of Business who will speak on "Inequality and World Economics," believes the integration of the world economy has helped reduce global income inequality on a "massive scale." Nonetheless, he says, the economic divide between rich and poor is getting larger within many countries, including virtually all developed nations. In his lecture, Spence says, he will try "to unpack the contributing factors to this inequality, its results, and how to respond effectively to this trend."

And Caltech's H. Jeff Kimble, the William L. Valentine Professor and professor of physics, will be focusing on "startling advances in quantum physics"—specifically, how the complex correlations that arise among many strongly interacting quantum objects has and can continue to shape computation, communication, and the health of physics and society more generally. 

Visit the Science and Society Conference website for more information about the event and to register and receive updates.

Written by Alex Roth

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Considering the Future
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On February 26, some of the nation's leading scientists and researchers will gather at Caltech to discuss some of the most perplexing questions facing humanity.
Wednesday, February 17, 2016
Noyes 147 (J. Holmes Sturdivant Lecture Hall) – Arthur Amos Noyes Laboratory of Chemical Physics

The Magic of Inquiry—from high school fundamentals to authentic research projects

Where Is Solar Energy Headed?

In a new paper in ScienceNate Lewis, the George L. Argyros Professor of Chemistry at Caltech, reviews recent developments in solar-energy utilization and looks at some of the challenges and opportunities that lie ahead in the research and development of solar-electricity, solar-thermal, and solar-fuels technologies. Read the full paper.

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Friday, January 29, 2016
Center for Student Services 360 (Workshop Space) – Center for Student Services

Course Ombudsperson Training, Winter 2016

Van Lehn Named to Forbes's 30 Under 30 List

Postdoctoral scholar Reid Van Lehn has been named to Forbes's annual 30 Under 30 list in the science category. The list honors 30 outstanding individuals under 30 years old in 20 different categories, from venture capital to sports to science. Van Lehn was recognized for his research on chemically engineered nanoparticles and their interactions with cell membranes.

"I'm honored to be included amongst this impressive list of scientists—both those named this year and in prior years," Van Lehn says. "I know many dedicated researchers both at Caltech and elsewhere who are deserving of such accolades, and I feel very fortunate to have been recognized for my contributions. I would especially like to thank my colleagues and advisors, who have had a profound effect on my education and research and have been immensely supportive throughout my career."

Van Lehn uses molecular simulation to study what happens when synthetic molecules—engineered nanoparticles injected into the body—and biological molecules interact with cell membranes. During his graduate work at MIT, he discovered a mechanism by which certain kinds of nanoparticles insert themselves into cell membranes, a finding that could have implications in novel drug delivery pathways. As a postdoc in Professor of Chemistry Tom Miller's group at Caltech, Van Lehn uses simulations to study how membrane proteins integrate into cell membranes via a protein-conducting channel called the Sec translocon.

This fall, Van Lehn will join the faculty at the University of Wisconsin–Madison, in its Department of Chemical and Biological Engineering. His research will focus on developing and utilizing new simulation methods to understand the interactions of bioactive materials and engineer novel nanoparticles for therapeutic applications.

When not in the lab, Van Lehn can be found avidly playing or watching sports. "I hail from Pittsburgh, so I primarily follow the Pittsburgh Steelers, Penguins, and Pirates," he says. "I also play pickup Ultimate Frisbee, and I can occasionally be seen being horribly outplayed in pickup basketball."

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Arnold and Mabel Beckman Foundation Furthers Legacy of Support

A $10 million gift from the Arnold and Mabel Beckman Foundation has created an endowment that will provide year-in, year-out support to graduate students at Caltech. Augmented by $5 million from the Gordon and Betty Moore Graduate Fellowship Match, the grant establishes the Beckman-Gray Graduate Student Fellowship Fund at Caltech.

The fellowships honor the foundation's cofounder Arnold O. Beckman (PhD '28) and its former chair, Harry B. Gray, who is the Arnold O. Beckman Professor of Chemistry and founding director of the Beckman Institute at Caltech.

Read the full story at giving.caltech.edu

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The Arnold and Mabel Beckman Foundation helps to create a fellowship fund for graduate students

Toward Liquid Fuels from Carbon Dioxide

In the quest for sustainable alternative energy and fuel sources, one viable solution may be the conversion of the greenhouse gas carbon dioxide (CO2) into liquid fuels.

Through photosynthesis, plants convert sunlight, water, and CO2 into sugars, multicarbon molecules that fuel cellular processes. CO2 is thus both the precursor to the fossil fuels that are central to modern life as well as the by-product of burning those fuels. The ability to generate synthetic liquid fuels from stable, oxygenated carbon precursors such as CO2 and carbon monoxide (CO) is reminiscent of photosynthesis in nature and is a transformation that is desirable in artificial systems. For about a century, a chemical method known as the Fischer-Tropsch process has been utilized to convert hydrogen gas (H2) and CO to liquid fuels. However, its mechanism is not well understood and, in contrast to photosynthesis, the process requires high pressures (from 1 to 100 times atmospheric pressure) and temperatures (100–300 degrees Celsius).

More recently, alternative conversion chemistries for the generation of liquid fuels from oxygenated carbon precursors have been reported. Using copper electrocatalysts, CO and CO2 can be converted to multicarbon products. The process proceeds under mild conditions, but how it takes place remains a mystery.

Now, Caltech chemistry professor Theo Agapie and his graduate student Joshua Buss have developed a model system to demonstrate what the initial steps of a process for the conversion of CO to hydrocarbons might look like.

The findings, published as an advanced online publication for the journal Nature on December 21, 2015 (and appearing in print on January 7, 2016), provide a foundation for the development of technologies that may one day help neutralize the negative effects of atmospheric accumulation of the greenhouse gas CO2 by converting it back into fuel. Although methods exist to transform CO2 into CO, a crucial next step, the deoxygenation of CO molecules and their coupling to form C–C bonds, is more difficult.

In their study, Agapie and Buss synthesized a new transition metal complex—a metal atom, in this case molybdenum, bound by one or more supporting molecules known as ligands—that can facilitate the activation and cleavage of a CO molecule. Incremental reduction of the molecule leads to substantial weakening of the C–O bonds of CO. Once weakened, the bond is broken entirely by introducing silyl electrophiles, a class of silicon-containing reagents that can be used as surrogates for protons.

This cleavage results in the formation of a terminal carbide—a single carbon atom bound to a metal center—that subsequently makes a bond with the second CO molecule coordinated to the metal. Although a carbide is commonly proposed as an intermediate in CO reductive coupling, this is the first direct demonstration of its role in this type of chemistry, the researchers say. Upon C–C bond formation, the metal center releases the C2 product. Overall, this process converts the two CO units to an ethynol derivative and proceeds easily even at temperatures lower than room temperature.

"To our knowledge, this is the first example of a well-defined reaction that can take two carbon monoxide molecules and convert them into a metal-free ethynol derivative, a molecule related to ethanol; the fact that we can release the C2 product from the metal is important," Agapie says.

While the generated ethynol derivative is not useful as a fuel, it represents a step toward being able to generate synthetic multicarbon fuels from carbon dioxide. The researchers are now applying the knowledge gained in this initial study to improve the process. "Ideally, our insight will facilitate the development of practical catalytic systems," Buss says.

The scientists are also working on a way to cleave the C–O bond using protons instead of silyl electrophiles. "Ultimately, we'd like to use protons from water and electron equivalents derived from sunlight," Agapie says. "But protons are very reactive, and right now we can't control that chemistry."

The research in the paper, "Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site," was funded by Caltech and the National Science Foundation.

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Caltech researchers gain insight into carbon monoxide coupling, one carbon atom at a time

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