Friday, February 13, 2015
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Backpocket Barnburner: A Lightning Quick Overview of Educational Theory

Caltech Professors Named Fellows of the AAAS

Caltech Professor of Astronomy George Djorgovski and chemist Bruce Brunschwig are among the 401 newly elected fellows of the American Association for the Advancement of Science (AAAS) for 2014.

The AAAS was formed in 1848 with the mission of "advancing science, engineering, and innovation throughout the world for the benefit of all people." The annual tradition of electing fellows began in 1874 to recognize scientists for their contributions toward this mission.

"The AAAS performs an essential role of promoting and protecting science and its benefits for society. This has never been more important than it is now," says Djorgovski, director of the Center for Data-Driven Discovery at Caltech. He was elected by his scientific peers to the AAAS's Section on Astronomy for his "leadership of the Virtual Observatory and the emerging field of astroinformatics, and considerable body of work on surveys and transient discovery." Astronomical data is exponentially growing in complexity and volume; the Virtual Observatory is an open, web-based research environment intended to organize, maintain, and explore the rich information content within these datasets.

"Science is being transformed by computing and information technology, and astronomy has been at the forefront of these developments," says Djorgovski.

Brunschwig, director of the Molecular Materials Research Center (MMRC) at Caltech, was elected to the AAAS's Section on Chemistry for his "pioneering contributions to the theoretical and physical understanding of electron transfer and its application to artificial photosynthesis." The MMRC is home to state-of-the-art instrumentation that facilitates cutting-edge interdisciplinary research in the fields of chemistry, surface science, and materials science. The center currently hosts myriad projects, including work on artificial photosynthesis and solar energy conversion.

"Bruce Brunschwig is a model for us to aspire to with his dedication to scholarship and his natural curiosity and inquisitiveness," says Brunschwig's colleague Nate Lewis, the George L. Argyros Professor of Chemistry at Caltech and the scientific director of the Joint Center for Artificial Photosynthesis. "His election as a fellow to the AAAS is well deserved."

Caltech is currently home to 42 fellows of the AAAS.

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Saturday, January 24, 2015
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The personal side of science

Wednesday, February 4, 2015
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Wednesday, February 18, 2015
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HALF TIME: A Mid-Quarter Meetup for TAs

How Do You Make a Greasy Protein?

Watson Lecture Preview

Every cell is encapsulated and protected by a thin membrane made of greasy molecules called lipids. Assemblies of equally greasy protein molecules span the membrane, forming passageways that control the flow of signaling molecules that, in turn, direct the cell's activities. Because of these proteins' key role in cell-to-cell communication, they have become a prime target for drug design. Professor of Biochemistry Bil Clemons is among those working out the structures of these proteins and, more fundamentally, the biological processes behind them. Clemons will discuss how cells assemble these proteins, and how they deliver them to the membrane, at 8 p.m. on Wednesday, January 7, in Caltech's Beckman Auditorium. Admission is free.

 

Q: What do you do?

A: I am nominally a structural biologist, but I'm really a crystallographer. We purify a protein in solution and then try to crystallize it, which is really, really hard. When we succeed, we make X-ray diffraction patterns of the crystals and work backwards from those patterns to calculate the precise position of every atom. This allows us to make a blueprint for the molecule, and the blueprint helps us understand how the molecule does what it does. That's my group's real interest—figuring out the biological mechanisms that underlie how a protein works. We want to understand, on a molecular level, the processes by which these proteins are targeted and inserted into the membrane.

Proteins are long chains of amino acids that assume very specific three-dimensional shapes, or conformations. The proteins we work on contain hundreds of amino acids and thousands of individual atoms. These proteins interact with other molecules as they do their jobs. When they do, their conformations change, so a large part of our work is trying to understand all these different interactions and motions.

A crystal contains millions of copies of the same molecule held in exactly one conformation, so in that sense, a crystal structure is just one snapshot of a series of biological motions. Eventually we'd like to make movies of all the conformational changes that occur during these interactions—or at least render the important frames. It's almost like producing a cheap cartoon, where the lead animator draws a few key cels, and the rest is filled in later.

 

Q: What do you get from a crystal structure?

A: We get the first glimpse of how something works. Every crystal structure provides a huge amount of information. The beauty of structural biology is that we get to be the first people to peek under the hood of a protein and draw a three-dimensional map of what we see. Science is vast, and most people work in very narrow fields, doing mechanistic studies and drug discovery and all sorts of things. Structural biologists create the platform for everyone else's studies.

 

Q: How did you get into this line of work?

A: Well, I'd like to say it was a series of happy accidents. I've always been passionate about science. In my heart, I think I was born a scientist. I always wanted to know how everything worked, and biochemistry fascinated me. There was so much complexity—so many ways to ask questions.

At Virginia Tech, I was lucky enough to have an undergraduate adviser, Walt Niehaus, who encouraged me to do research in his group. There was really no looking back after that. I just thought, "Wow. This is really fun. I like doing this." Meanwhile, I was paying my way through school. My senior year I was the student manager of one of the food-service facilities. I was working nearly 40 hours a week managing 40 employees plus spending another 20 hours in the lab and 20 hours in school. I wasn't able to look past that to what my future might be, but Walt pushed me to apply for grad school. It was eye-opening the first time he suggested I could do this for a living.

Walt's research was in basic biochemistry. There weren't any structural biologists at Virginia Tech at the time, but the Howard Hughes Medical Institute sent us a booklet with stereo pictures of protein structures. I thought, "You've got to be kidding me. We can look at these things in 3-D?" It blew my mind. So I went to grad school at the University of Utah to be a crystallographer, and I earned my PhD working on the molecular machinery responsible for making proteins. Then I did my postdoctoral work at Harvard Med, trying to understand the complex process of getting greasy membrane proteins into cell membranes. We solved the structure of an important piece of the puzzle there, and now that I'm at Caltech, which has major strengths in X-ray crystallography, we're filling in the details of the bigger picture.

 

 

Named for the late Caltech professor Earnest C. Watson, who founded the series in 1922, the Watson Lectures present Caltech and JPL researchers describing their work to the public. Many past Watson Lectures are available online at Caltech's iTunes U site.

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Douglas Smith
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Tuesday, December 2, 2014
Guggenheim 101 (Lees-Kubota Lecture Hall)

PUSD: Annual Open Enrollment

New Center Supports Data-Driven Research

With the advanced capabilities of today's computer technologies, researchers can now collect vast amounts of information with unprecedented speed. However, gathering information is only one half of a scientific discovery, as the data also need to be analyzed and interpreted. A new center on campus aims to hasten such data-driven discoveries by making expertise and advanced computational tools available to Caltech researchers in many disciplines within the sciences and the humanities.

The new Center for Data-Driven Discovery (CD3), which became operational this fall, is a hub for researchers to apply advanced data exploration and analysis tools to their work in fields such as biology, environmental science, physics, astronomy, chemistry, engineering, and the humanities.

The Caltech center will also complement the resources available at JPL's Center for Data Science and Technology, says director of CD3 and professor of astronomy George Djorgovski.

"Bringing together the research, technical expertise, and respective disciplines of the two centers to form this joint initiative creates a wonderful synergy that will allow us opportunities to explore and innovate new capabilities in data-driven science for many of our sponsors," adds Daniel Crichton, director of the Center for Data Science and Technology at JPL.

At the core of the Caltech center are staff members who specialize in both computational methodology and various domains of science, such as biology, chemistry, and physics. Faculty-led research groups from each of Caltech's six divisions and JPL will be able to collaborate with center staff to find new ways to get the most from their research data. Resources at CD3 will range from data storage and cataloguing that meet the highest "housekeeping" standards, to custom data-analysis methods that combine statistics with machine learning—the development of algorithms that can "learn" from data. The staff will also help develop new research projects that could benefit from large amounts of existing data.

"The volume, quality, and complexity of data are growing such that the tools that we used to use—on our desktops or even on serious computing machines—10 years ago are no longer adequate. These are not problems that can be solved by just buying a bigger computer or better software; we need to actually invent new methods that allow us to make discoveries from these data sets," says Djorgovski.

Rather than turning to off-the-shelf data-analysis methods, Caltech researchers can now collaborate with CD3 staff to develop new customized computational methods and tools that are specialized for their unique goals. For example, astronomers like Djorgovski can use data-driven computing in the development of new ways to quickly scan large digital sky surveys for rare or interesting targets, such as distant quasars or new kinds of supernova explosions—targets that can be examined more closely with telescopes, such as those at the W. M. Keck Observatory, he says.

Mary Kennedy, the Allen and Lenabelle Davis Professor of Biology and a coleader of CD3, says that the center will serve as a bridge between the laboratory-science and computer-science communities at Caltech. In addition to matching up Caltech faculty members with the expertise they will need to analyze their data, the center will also minimize the gap between those communities by providing educational opportunities for undergraduate and graduate students.

"Scientific development has moved so quickly that the education of most experimental scientists has not included the techniques one needs to synthesize or mine large data sets efficiently," Kennedy says. "Another way to say this is that 'domain' sciences—biology, engineering, astronomy, geology, chemistry, sociology, etc.—have developed in isolation from theoretical computer science and mathematics aimed at analysis of high-dimensional data. The goal of the new center is to provide a link between the two."

Work in Kennedy's laboratory focuses on understanding what takes place at the molecular level in the brain when neuronal synapses are altered to store information during learning. She says that methods and tools developed at the new center will assist her group in creating computer simulations that can help them understand how synapses are regulated by enzymes during learning.

"The ability to simulate molecular mechanisms in detail and then test predictions of the simulations with experiments will revolutionize our understanding of highly interconnected control mechanisms in cells," she says. "To some, this seems like science fiction, but it won't stay fictional for long. Caltech needs to lead in these endeavors."

Assistant Professor of Biology Mitchell Guttman says that the center will also be an asset to groups like his that are trying to make sense out of big sets of genomic data. "Biology is becoming a big-data science—genome sequences are available at an unprecedented pace. Whereas it took more than $1 billion to sequence the first genome, it now costs less than $1,000," he says. "Making sense of all this data is a challenge, but it is the future of biomedical research."

In his own work, Guttman studies the genetic code of lncRNAs, a new class of gene that he discovered, largely through computational methods like those available at the new center. "I am excited about the new CD3 center because it represents an opportunity to leverage the best ideas and approaches across disciplines to solve a major challenge in our own research," he says.

But the most valuable findings from the center could be those that stem not from a single project, but from the multidisciplinary collaborations that CD3 will enable, Djorgovski says. "To me, the most interesting outcome is to have successful methodology transfers between different fields—for example, to see if a solution developed in astronomy can be used in biology," he says.

In fact, one such crossover method has already been identified, says Matthew Graham, a computational scientist at the center. "One of the challenges in data-rich science is dealing with very heterogeneous data—data of different types from different instruments," says Graham. "Using the experience and the methods we developed in astronomy for the Virtual Observatory, I worked with biologists to develop a smart data-management system for a collection of expression and gene-integration data for genetic lines in zebrafish. We are now starting a project along similar methodology transfer lines with Professor Barbara Wold's group on RNA genomics."

And, through the discovery of more tools and methods like these, "the center could really develop new projects that bridge the boundaries between different traditional fields through new collaborations," Djorgovski says.

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Caltech and City of Hope Formalize Collaboration

Caltech and City of Hope have signed a memorandum of understanding, formalizing a relationship that encourages researchers from the two institutions to collaborate and share resources in the interest of furthering both basic scientific research and translational projects—those with a medical application.

"Bringing together Caltech and City of Hope researchers will surely result in transformative science and hopefully also new approaches to medical care," says Jacqueline K. Barton, the Arthur and Marian Hanisch Memorial Professor of Chemistry and chair of the Division of Chemistry and Chemical Engineering at Caltech.

"The complementary nature of this partnership is a natural fit between our two institutions," says David Horne, vice provost and associate director of the Beckman Research Institute at City of Hope. "The translational opportunities in therapeutics and devices have never been greater, and this partnership comes at an opportune time to advance health care in oncology, diabetes, and HIV, which are City of Hope's major focus areas."

As a result of the new agreement, City of Hope researchers will have access to several unique Caltech facilities, including the Molecular Observatory, an X-ray crystallography resource with an automated beamline at the Stanford Synchrotron Radiation Laboratory; the Center for Catalysis and Chemical Synthesis, a synthetic-chemistry center that offers robotic instrumentation for high-throughput screening and analysis of chemical entities; and the Center for the Chemistry of Cellular Signaling, which analyzes the systems of molecules that dictate how cells behave and react to their surroundings.

Likewise, Caltech scientists and engineers will be able to access City of Hope's array of core research services, including resources such as the Pathology Core, a facility that provides access to preserved tumors and normal tissues; the Analytical Pharmacology Core Facility, which conducts pharmacokinetic and pharmacodynamic studies for chemotherapy clinical trials and peer-reviewed preclinical studies; the Animal Tumor Model Core, which creates various cancer models in mice for testing novel experimental therapies; and the Translational Research Laboratory, which helps with the design of clinical trials and basic research studies using samples from clinical trials.

"This is a very timely event, and I see it as building a bridge between Caltech and City of Hope that is natural both in proximity and in the way we complement each other," says Peter Dervan, Caltech's Bren Professor of Chemistry. "Caltech has always been very strong in basic fundamental research. But today, Caltech scientists and engineers are genuinely interested in taking the discoveries that we make in chemistry, biochemistry, biology, and bioengineering to real-world practical applications. City of Hope is a renowned medical research center that is only 20 minutes away and can work with us collaboratively on these translational problems. This is going to be a win-win partnership."

The memorandum establishes the Arthur D. Riggs Distinguished Lectureship series, which will bring scientists from across the country to speak at Caltech and City of Hope on current projects in basic research as well as on efforts to predict, prevent, diagnose, treat, and cure such diseases as cancer, diabetes, and HIV.

The first lecture in that series will be delivered on Wednesday, November 19, by a distinguished molecular biologist who knows both Caltech and City of Hope well: Riggs himself. Riggs completed his doctoral work in biochemistry at Caltech in 1966; at City of Hope, he is now a professor of cancer biology and chair of the Department of Diabetes and Metabolic Diseases Research as well as director emeritus of the Beckman Research Institute at City of Hope.

"We are really excited that Art has agreed to be the kickoff lecturer," says Dervan. "By sharing interest in the lectures, researchers at Caltech and City of Hope will share ideas, and I think at the end of the day we're going to be sharing students—postdoctoral coworkers and graduate students—on collaborative projects."

Riggs's lecture, " Reflections on a Career of Collaboration, Mostly with Caltech," will begin at 4 p.m. in Gates Annex 22 at Caltech and is open to the public.

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Kimm Fesenmaier
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Wednesday, October 29, 2014
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