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California Institute of Technology

California Institute of Technology

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The California Institute of Technology (Caltech) is a private research university situated in Pasadena, California. Caltech has six academic divisions with strong emphasis on science and engineering. Its 124-acre primary campus is located approximately 11 mi northeast of downtown Los Angeles.

Founded as a preparatory and vocational school by Amos G. Throop in 1891, the college attracted leading early 20th-century scientists such as Robert Andrews Millikan and George Ellery Hale. Despite its relatively small size, 31 Caltech alumni and faculty have won the Nobel Prize and 66 have won the United States National Medal of Science or Technology. There are 110 faculty members who have been elected to the National Academies. Caltech managed $333 million in sponsored research in 2011 and $1.76 billion for its endowment in 2012.

Caltech was ranked first in the 2012–2013 Times Higher Education World University Rankings for the second year running, as well as ranking first in Engineering & Technology and Physical Sciences.

Honors: A Technology Powerhouse

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Caltech News

Caltech News

New chemistry professor is at the frontier of new visualization toolsNews Writer: Whitney Clavin Lu WeiCredit: Caltech

Caltech's new assistant professor of chemistry Lu Wei is pushing the boundaries of imaging cells. She is developing new spectroscopy and microscopy techniques to track molecules in real time inside cells, and to visualize them in dozens of different colors. Though her primary focus is to create next-generation tools for biologists, Wei also plans to apply these tools to the complex environments of biological samples, such as brain tissues.

Wei grew up in the city of Wuhan in central China. She received her BS from Nanjing University in 2010 and her PhD from Columbia University in 2015. She came to Caltech as a visiting associate in 2017 and became an assistant professor in 2018.

We sat down with Wei to talk about her chemistry research and to learn more about one of her favorite Pasadena-area restaurants.

What kinds of microscopy techniques are you developing?

We make use of physical chemistry principles to develop microscopy methods that enable us to visualize the dynamics inside cells.

One method we are working on is vibrational spectroscopy, where we detect the vibrations of certain chemical bonds. For example, we have utilized a class of small chemical tags—such as those with certain types of carbon bonds, including carbon-carbon triple bonds—to detect small biomolecules of interest in live cells. Because these chemical bonds are not normally found in cells, and because they vibrate at a special frequency where none of the molecules in cells vibrate, they can be specifically tracked. We can attach these tiny chemical tags to small biomolecules of interest such as neurotransmitters, nucleic acids, and amino acids, to visualize where these small molecules are in living cells.

How does this technique differ from others used for imaging cells?

A common method in bioimaging is fluorescence microscopy, which involves the protein called green fluorescent protein, or GFP, which was the subject of the 2008 Nobel Prize in Chemistry. GFP glows with a green color and is therefore used as a tag to visualize the insides of cells. However, GFP is a large molecule and is mostly suitable for tagging proteins. Using it as a tag for smaller biomolecules poses the risk of changing the properties of these functional molecules in cells. Our method better retains the properties of these small molecules.

What are some applications of this technique?

We can use our microscopy methods on all kinds of biological tissues to understand activities inside the very complex environments of cells. For example, one application of our method in neurobiology is to visualize the metabolism that goes on in brain tissues involved in degenerative diseases. Because our tools are devised for living cells, they can help us and other researchers trace and understand the changes in metabolic dynamics of diseased brain tissues with high spatial and temporal precision. This will help us gain more insight into the causes and possible treatments for these diseases.

What other methods are you working on?

We want to be able to visualize multiple components in a cellular environment at the same time. This would allow us to understand the relationships and interactions of a variety of the machineries inside cells. We have developed a laser-based microscopy technique called pre-resonance Raman spectroscopy that allows us to achieve a multicolor imaging capability. As a comparison, in fluorescence imaging, the spectral lines—the signatures from the different molecules—are broad and therefore easily overlap with each other, and this limits the total number of molecules that can be resolved in the visible-light range. With our Raman spectroscopy technique, we have created molecules with sharp peaks, allowing us to view them in up to 24 colors.

So far, we can visualize eight colors—corresponding to eight kinds of biomolecules participating in cellular activity at a time in a cell or tissue. These targets include proteins like alpha-tubulin, which makes up microtubules, major structural components of cells. We expect to be able to do even more colors in the near future.Our general goal is to push the frontiers of bioimaging. We want to be able to visualize something that we couldn't see before.

How do you like Caltech so far?

I really like being at a small campus, where basically anywhere is within a 10-minute walk. It's very convenient for talking to other people and setting up interdisciplinary collaborations. It's a dream place to be for any scientist.

How do you like Pasadena?

It's a really nice place, the climate is great, and I like the food. We just went to a nice place for dinner in Arcadia called Meizhou Dongpo with some faculty. Meizhou is a place in Sichuan Province in China and Dongpo was a very famous Chinese poet who also happened to be a good cook, so that's why the restaurant is named after him. There is a lot of good Chinese food around here!

Fri, 16 Nov 2018
New insights into how an ordinary stem cell becomes a powerful immune agentNews Writer: Lori Dajose This "heat map" figure shows how removing Bcl11b affects gene expression at the stage when Bcl11b first begins to work. Each column of colored lines shows data from a different mouse, and the key at the bottom shows whether the mouse had both copies of its Bcl11b gene intact (+/+), just one copy intact (+/-), or both copies deleted (KO). Each horizontal line represents a gene—red indicates expression increased, blue indicates expression decreased.Credit: Courtesy of Maile Romero-WolfThe Big Question

How do individual developing cells choose and commit to their "identity"—to become, for example, an immune cell, or a muscle cell, or a neuron?

The Background

T-lymphocytes are cells in the immune system that act as "intelligence agents"—they circulate throughout the body, detect threats, and determine what kind of response the immune system should make. These cells are crucial in certain cancer therapies in which they are persuaded to attack cancerous cells.

When a stem cell finalizes its decision to develop into a T-lymphocyte, a particular gene called Bcl11b turns on and stays on. There is a drastic difference in gene expression patterns and in developmental options between cells that have activated Bcl11b and those that haven't. The gene's activation signals a turning point, a commitment to the T-lymphocyte developmental path. But what is Bcl11b doing to create such profound changes?

The Discoveries

Now, a Caltech-led team of scientists has revealed the mechanisms that enable Bcl11b to affect gene regulation in order to control a cell's commitment to developing into a T-lymphocyte. The work was done in the laboratory of Ellen Rothenberg, Albert Billings Ruddock Professor of Biology. A paper describing the research appeared online on October 30 in the journal Nature Immunology.

"These findings should be valuable both for immunologists seeking to understand the diversity and stability of different immune cell types and for researchers interested in how to read the regulatory code in the genome and use it to predict development," says Rothenberg. "Our findings emphasize that development does not just turn on and off single regulatory factors, but also it makes new ensembles of regulatory factors available to modify the action of pre-existing factors. Our study shows that it is the ensembles of these factors that are crucial to characterize in order to explain the cells' behavior."

The Impact

Bcl11b and its partners play roles not only in a variety of immune functions but also in the processes that prevent the development of leukemia. These new findings should offer ways to one day improve cell engineering and possibly even to reverse some tumor characteristics.

The Details

Bcl11b is a gene regulation protein: It binds to specific regions on the genome in order to modulate gene expression—that is, to tune up or down the levels of particular genes. The Bcl11b gene is activated for the first time in a cell's lifetime as an immature stem cell goes through a "commitment" process of becoming a T-lymphocyte, and the gene continues to be expressed throughout the cell's lifetime. This new research demonstrates how the Bcl11b protein works to enforce commitment and, more broadly, how the genome controls development.

The first question Rothenberg and her team sought to answer was where on the genome Bcl11b works. The Bcl11b protein is found "hanging around," binding to DNA throughout the genome, Rothenberg says, but the target genes for which Bcl11b binding actually impacts gene expression were not clear before this work. The new research demonstrates, however, that the question could be answered by looking at how Bcl11b operates as a partner of other proteins in gene-regulation complexes. It is not sufficient to simply find locations on the genome where Bcl11b directly binds—the best clues have come from identifying sites where Bcl11b protein is needed to "recruit" other partner proteins to bind with it.

Secondly, the team showed that Bcl11b works indirectly to affect a complex cascade of gene regulation in order to force a cell to commit to the T-lymphocyte developmental path. For example, a gene called E2A, active during immune cell development, produces a protein with totally different functions than Bcl11b. Though Bcl11b does not directly bind to the E2A gene, the new research shows that Bcl11b indirectly helps E2A by suppressing another protein which actively interferes with E2A.

"Bcl11b has direct and indirect partnerships with other proteins throughout the genome—it can directly increase or decrease their production, which in turn indirectly tunes the levels of other affected proteins," says Rothenberg. "Gene regulatory protein activities depend not only on their own expression but also on the presence or absence of other factors that collaborate with them in a network. These dynamic partnerships are crucial to explain development."

The paper is titled "Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16." The first authors are Hiroyuki Hosokawa, former Caltech senior postdoctoral scholar now at Tokai University School of Medicine in Japan, and Maile Romero-Wolf, research technician assistant. Other co-authors are Mary Yui, research professor of biology and biological engineering; Jonas Ungerbäck, a former Caltech postdoctoral scholar now at Lund University in Sweden; research technician associate Maria Quiloan; Masaki Matsumoto and Keiichi Nakayama of Kyushu University in Japan; and Tomoaki Tanaka of Chiba University in Japan. Funding was provided by the Manpei Suzuki Diabetes Foundation, the U.S. Public Health Service, Grants-in-Aid for Advanced Research and Development Programs for Medical Innovation, the Takeda Science Foundation, the SENSHINE Medical Research Foundation, the Swedish Research Council, the California Institute of Regenerative Medicine Bridges to Stem Cell Research Program, the Louis A. Garfinkle Memorial Laboratory Fund and the Al Sherman Foundation, the provost and Division of Biology and Biological Engineering at Caltech, and the Albert Billings Ruddock Professorship.

Related Links: How a Thieving Transcription Factor Dominates the Genome
Thu, 15 Nov 2018
A candidate progenitor star to a "type Ic" supernova has been identified for the first timeNews Writer: Whitney Clavin This artist’s concept illustrates a possible progenitor star to supernova 2017ein—a blue supergiant star that once existed inside a cluster of young stars in the spiral galaxy NGC 3938, located 65 million light-years away. It would have exploded as a supernova in 2017.Credit: NASA, ESA, and J. Olmsted (STScI)

Supernovas are the deathly explosions of massive stars. One of the ways that astronomers look for clues about how these stars blow up is to go hunting for what's known as the progenitor to a supernova—the star before it died. They comb through archival telescope images and try to pinpoint the location and identity of the star before it blasted apart. Now, for the first time, a Caltech-led team has likely found such a progenitor for a supernova class known as "type Ic" (pronounced "one-C"). Of all the classes of supernovas, this is the only one that did not have a known progenitor until now and thus its identification was thought of as something of a Holy Grail by astronomers. 

The type Ic supernova, called SN 2017ein, was initially discovered in May 2017 by researchers using the Tenagra Observatories in Arizona. It is located in a spiral galaxy called NGC 3938, about 65 million light-years away. The Caltech astronomy team was able to track down this supernova's progenitor using archival images from NASA's Hubble Space Telescope, taken in 2007.

"An alert was sent out when the supernova was initially found," says Schuyler Van Dyk, a staff scientist at IPAC, a science and data center for astronomy at Caltech. "You can't sleep once that happens and have to mobilize to try to find the progenitor to the explosion. Within a few weeks after the supernova was discovered, we found a candidate using both new and archival Hubble images." Van Dyk is lead author of a paper about the findings, published this summer in The Astrophysical Journal. "The new images were essential for pinpointing the candidate progenitor's location."

The progenitor is hot and luminous and is thought to be either a single hefty star 48 or 49 times the mass of our sun or a massive binary star system in which the star that exploded weighs between 60 and 80 solar masses.

"Type Ic supernovas occur with the most massive of stars," says Van Dyk. "But we were surprised by how massive this one appears to be, and especially by the possibility of a massive double-star system as the progenitor. Although theories have existed for the last three decades that type Ic supernovas could be the explosions of very massive single stars, alternative, more recent theories point toward stars of lower mass in binary systems as being the origins of these explosions."

Other supernova classes include type Ia, which occur when white dwarfs in binary star systems explode (cosmologists used these to discover that our universe is not only expanding but accelerating apart). Type II, type Ib, and Ic supernovas occur when massive stars collapse at the end of their lives, forming neutron stars or black holes. Type Ib and Ic differ from type II in that their progenitor stars lose outer envelopes of material around their central cores before exploding. Type Ib and Ic supernovas differ from each other slightly in chemical composition. 

Piecing together how each of these supernova types occurs provides a better understanding of the evolution of the most massive stars in our universe. 

"The origins of such explosions are relevant to the entire astronomical community, not just supernova researchers," says Ori Fox from the Space Telescope Science Institute (STScI), a co-author on the study. "The results have implications on ideas from star formation to stellar evolution and feedback into the galaxy."

"Astronomers have been trying to find this progenitor for some 20 years," says Van Dyk. "Humans wouldn't be here without supernovas—they make the chemical elements from which we are made." 

The astronomers say that they should be able to confirm with certainty whether they have identified the correct progenitor to the type Ic explosion within a few years, using Hubble or the upcoming NASA James Webb Space Telescope, set to launch in 2021. As the supernova fades as expected, the astronomers will have a clearer view of the area around it. If the luminous progenitor candidate was correctly identified in archival images, then it will have vanished and should not be seen in the new images. If the scientists still see the candidate progenitor, that means it was misidentified and some other hidden star was the culprit. 

The study, titled, "SN 2017ein and the Possible First Identification of a Type Ic Supernova Progenitor," was funded by NASA, the National Science Foundation, the Tabasgo Foundation, the Christopher R. Redlich Fund, and the Miller Institute for Basic Research in Science.

Related Links: News release and images for SN 2017ein from Hubble Space Telescope
Wed, 14 Nov 2018
An artist's concept of interstellar asteroid 1I/2017 U1 ('Oumuamua) as it passed through the solar system after its discovery in October 2017. Observations of 'Oumuamua indicate that it must be very elongated because of its dramatic variations in brightness as it tumbled through space.Credit: European Southern Observatory / M. Kornmesser

In November 2017, scientists pointed NASA's Spitzer Space Telescope toward the object known as 'Oumuamua—the first known interstellar object to visit our solar system. The infrared-sensing Spitzer was one of many telescopes pointed at 'Oumuamua in the weeks after its discovery that October.

'Oumuamua was too faint for Spitzer to detect when it looked more than two months after the object's closest approach to Earth in early September. However, the "non-detection" puts a new limit on how large the strange object can be. The results are reported in a new study published today in The Astronomical Journal and coauthored by scientists at several universities, including the Jet Propulsion Laboratory, which is managed by Caltech for NASA, and IPAC, a data and science center for astronomy at Caltech. 

The new size limit is consistent with the findings of a research paper published earlier this year, which suggested that outgassing was responsible for the slight changes in 'Oumuamua's speed and direction as it was tracked last year: The authors of that paper conclude the expelled gas acted like a small thruster gently pushing the object. 

"'Oumuamua has been full of surprises from day one, so we were eager to see what Spitzer might show," said David Trilling, lead author on the new study and a professor of astronomy at Northern Arizona University. "The fact that 'Oumuamua was too small for Spitzer to detect is actually a very valuable result."

Read the full story from JPL News.

Related Links: Spitzer Space Telescope Website
Wed, 14 Nov 2018
News Writer: Shayna Chabner McKinney Members of the Butkovich family, left to right, Koba, Vicktor, Maria, and Lazarina, gathered together during Caltech Family Weekend. In addition to two Caltech alumnae in the family, Koba and Lazarina are current students, while the youngest member of the family, Vicktor, has his own aspirations to attend. Credit: Courtesy of Bill Youngblood

The families of Caltech's newest undergraduates were welcomed to the community and provided a glimpse of Caltech's undergraduate program during the Institute's annual Family Weekend event.

Between Friday, November 9, and Sunday, November 11, more than 100 families explored campus and participated in events and activities that included a parents' happy hour at the Athenaeum's Rathskeller as well as panel discussions and presentations with Student Affairs administrators, faculty, and students on undergraduate life, opportunities for studying abroad, summer research, career planning, academics, and a look at what the Caltech experience is like for student athletes. Families and their students were also invited to attend a Von Kármán Lecture and a performance by the Caltech-Occidental Wind Orchestra.

During a luncheon held in the dining hall of Caltech's recently opened Bechtel Residence, President Thomas Rosenbaum greeted the families with a message that highlighted the range of opportunities and experiences undergraduate students' have—from the close interaction with faculty and peers to hands-on research—to broaden their thinking and perspective while also helping to advance discoveries that have the potential to positively change the world. 

"Thank you for sharing your children with us," Rosenbaum said. "We are really excited that they are bringing their energy, their intellect, their idealism to our community, and we look forward to many years of discovery."

Tue, 13 Nov 2018
Event highlighted projects focused on cardiovascular health and tumor tracking News Writer: Emily Velasco Credit: Shutterstock

Ten years ago, Caltech and City of Hope forged a partnership that combined what each institute was best at—engineering and medicine, respectively—with the goal of developing new biomedical technologies.

This October, researchers came together to celebrate the 10th anniversary of the Caltech-City of Hope Biomedical Research Initiative and highlight recent noteworthy projects funded by the initiative.

This year's featured projects were:

• Assessing cardiovascular health and testing for the presence of metabolic disease using a handheld device developed by Mory Gharib (PhD '83), the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering. The research is being conducted by Joanne Mortimer, a professor and researcher at City of Hope, and Danny Petrasek, a visiting associate and lecturer in medical engineering at Caltech.

• A system for tracking the location of tumors during surgery using implantable magnetic beacons and a sensor array placed near the area being operated on. The system is being developed by Yu-Chong Tai, Caltech's Anna L. Rosen Professor of Electrical Engineering and Medical Engineering, Andrew and Peggy Cherng Medical Engineering Leadership Chair, and executive officer for medical engineering; and Yuman Fong, a professor and surgeon at City of Hope.

In all, the initiative has funded 53 collaborations between researchers at Caltech and City of Hope. They include research into early detection of breast cancer, a treatment for HIV, and research into the effects gut microbes have on the immune system, among many others. It involves researchers from the divisions of Engineering and Applied Science, Biology and Biological Engineering, and Chemistry and Chemical Engineering.

Related Links: Partners in InnovationMedical Engineering - ENGenious
Tue, 13 Nov 2018
UCLA/Caltech team uncovers a new and simple way to learn the structures of small moleculesNews Writer: Whitney Clavin Graduate student Tyler Fulton prepares samples of small molecules in a lab at Caltech.Credit: Caltech

In a new study that one scientist called jaw-dropping, a joint UCLA/Caltech team has shown that it is possible to obtain the structures of small molecules, such as certain hormones and medications, in as little as 30 minutes. That's hours and even days less than was possible before. 

The team used a technique called micro-electron diffraction (MicroED), which had been used in the past to learn the 3-D structures of larger molecules, specifically proteins. In this new study, the researchers show that the technique can be applied to small molecules, and that the process requires much less preparation time than expected. Unlike related techniques—some of which involve growing crystals the size of salt grains—this method, as the new study demonstrates, can work with run-of-the-mill starting samples, sometimes even powders scraped from the side of a beaker. 

"We took the lowest-brow samples you can get and obtained the highest-quality structures in barely any time," says Caltech professor of chemistry Brian Stoltz, who is a co-author on the new study, published in the journal ACS Central Science"When I first saw the results, my jaw hit the floor." Initially released on the pre-print server ChemRxiv in mid-October, the article has been viewed more than 35,000 times.  

The reason the method works so well on small-molecule samples is that while the samples may appear to be simple powders, they actually contain tiny crystals, each roughly a billion times smaller than a speck of dust. Researchers knew about these hidden microcrystals before, but did not realize they could readily reveal the crystals' molecular structures using MicroED. "I don't think people realized how common these microcrystals are in the powdery samples," says Stoltz. "This is like science fiction. I didn't think this would happen in my lifetime—that you could see structures from powders."


This movie is an example of electron diffraction (MicroED) data collection, in which electrons are fired at a nanocrystal while being continuously rotated. Data from the movie are ultimately converted to a 3-D chemical structure. Credit: UCLA/Caltech

The results have implications for chemists wishing to determine the structures of small molecules, which are defined as those weighing less than about 900 daltons. (A dalton is about the weight of a hydrogen atom.) These tiny compounds include certain chemicals found in nature, some biological substances like hormones, and a number of therapeutic drugs. Possible applications of the MicroED structure-finding methodology include drug discovery, crime lab analysis, medical testing, and more. For instance, Stoltz says, the method might be of use in testing for the latest performance-enhancing drugs in athletes, where only trace amounts of a chemical may be present. 

"The slowest step in making new molecules is determining the structure of the product. That may no longer be the case, as this technique promises to revolutionize organic chemistry," says Robert Grubbs, Caltech's Victor and Elizabeth Atkins Professor of Chemistry and a winner of the 2005 Nobel Prize in Chemistry, who was not involved in the research. "The last big break in structure determination before this was nuclear magnetic resonance spectroscopy, which was introduced by Jack Roberts at Caltech in the late '50s."

Like other synthetic chemists, Stoltz and his team spend their time trying to figure out how to assemble chemicals in the lab from basic starting materials. Their lab focuses on such natural small molecules as the fungus-derived beta-lactam family of compounds, which are related to penicillins. To build these chemicals, they need to determine the structures of the molecules in their reactions—both the intermediate molecules and the final products—to see if they are on the right track.

One technique for doing so is X-ray crystallography, in which a chemical sample is hit with X-rays that diffract off its atoms; the pattern of those diffracting X-rays reveals the 3-D structure of the targeted chemical. Often, this method is used to solve the structures of really big molecules, such as complex membrane proteins, but it can also be applied to small molecules. The challenge is that to perform this method a chemist must create good-sized chunks of crystal from a sample, which isn't always easy. "I spent months once trying to get the right crystals for one of my samples," says Stoltz.

Another reliable method is NMR (nuclear magnetic resonance), which doesn't require crystals but does require a relatively large amount of a sample, which can be hard to amass. Also, NMR provides only indirect structural information. 

Before now, MicroED—which is similar to X-ray crystallography but uses electrons instead of X-rays—was mainly used on crystallized proteins and not on small molecules. Co-author Tamir Gonen, an electron crystallography expert at UCLA who began developing the MicroED technique for proteins while at the Howard Hughes Medical Institute in Virginia, said that he only started thinking about using the method on small molecules after moving to UCLA and teaming up with Caltech. 

"Tamir had been using this technique on proteins, and just happened to mention that they can sometimes get it to work using only powdery samples of proteins," says Hosea Nelson (PhD '13), an assistant professor of chemistry and biochemistry at UCLA. "My mind was blown by this, that you didn't have to grow crystals, and that's around the time that the team started to realize that we could apply this method to a whole new class of molecules with wide-reaching implications for all types of chemistry."

The team tested several samples of varying qualities, without ever attempting to crystallize them, and were able to determine their structures thanks to the samples' ample microcrystals. They succeeded in getting structures for ground-up samples of the brand-name drugs Tylenol and Advil, and they were able to identify distinct structures from a powdered mixture of four chemicals. 

The UCLA/Caltech team says it hopes this method will become routine in chemistry labs in the future. 

"In our labs, we have students and postdocs making totally new and unique molecular entities every day," says Stoltz. "Now we have the power to rapidly figure out what they are. This is going to change synthetic chemistry."  

The study, "The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination," was funded by the National Science Foundation, the National Institutes of Health, the Department of Energy, a Beckman Young Investigators award, a Searle Scholars award, a Pew Scholars award, the Packard Foundation, the Sloan Foundation, the Pew Charitable Trusts, and the Howard Hughes Medical Institute. Other co-authors include Christopher Jones,Michael Martynowycz, Johan Hattne, and Jose Rodriguez of UCLA; and Tyler Fulton of Caltech. 

Mon, 12 Nov 2018
Hundreds turn out to celebrate Frances Arnold, winner of the 2018 Nobel Prize in ChemistryNews Writer: Jon Nalick Frances Arnold at the November 8, 2018 campus celebration event.Credit: Caltech

Many members of the Caltech community, along with local elected officials, gathered along the Olive Walk on November 8 to honor Frances Arnold, who recently received the 2018 Nobel Prize in Chemistry for the "directed evolution of enzymes."

During the mid-morning ceremony, Arnold, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, told the crowd she felt "incredibly lucky and grateful" to have worked for more than 30 years at Caltech—"a very small and special institution that made it possible for me to do the work that led to the Nobel Prize."

Arnold, who is also the director of the Donna and Benjamin M. Rosen Bioengineering Center, added, "Only here could I convince students from very different disciplines—engineers, chemists, biochemists, molecular biologists, computational scientists—to throw their hat into this ring and this completely unexplored field, and contribute their creativity to this kooky idea that you could breed proteins like you can breed cats and dogs. And only here would I have been challenged to solve ever harder problems."

"Today is a great celebration for Caltech," Jacqueline Barton, the John G. Kirkwood and Arthur A. Noyes Professor of Chemistry and the Norman Davidson Leadership Chair in the Division of Chemistry and Chemical Engineering, told the crowd honoring Arnold. "It's a celebration of science. It's a celebration of chemistry. It's a celebration of the Division of Chemistry and Chemical Engineering. It's a celebration of our students. … It is also a celebration for women at Caltech. Frances very much deserves this celebration."

Addressing the crowd from the podium, President Thomas Rosenbaum praised Arnold, saying that she exemplifies "the qualities we hold dear: excellence, fearlessness, reinvention, seizing the big idea, trampling disciplinary boundaries, connecting fundamental understanding of nature to technological innovation. Her revolution in evolution has set the stage for new types of chemistries and greener pathways for chemicals."

"We thank Frances for this excuse to party," he added, to applause and laughter from the audience, "but most of all for the joy that she brings to discovery."

Related Links: VIDEO: A Day with Caltech's 2018 Nobel LaureateFrances Arnold Wins 2018 Nobel Prize in Chemistry
Fri, 09 Nov 2018
Caltech researchers identify the neural basis of threatening and aggressive behaviors in DrosophilaNews Writer: Lori Dajose A fruit fly raising its wings in a threat display.Credit: Courtesy of the Anderson laboratory

You can always tell when two guys are about to get into a fight. It starts with angry stares, puffed-out chests, arms tossed out to the side, and little, aggressive starts forward. Neuroscientists call the combination of these physical movements "threat displays," and they are seen in countless organisms, from humans to tiny Drosophila fruit flies. Caltech researchers have now identified a small cluster of neurons in the male fly brain that governs this threatening behavior. Their work provides a starting point that may lead to greater understanding of threatening behaviors and aggression in humans.

The work was led by senior postdoctoral scholar Brian Duistermars and carried out in the laboratory of David Anderson, the Seymour Benzer Professor of Biology, Tianqiao and Chrissy Chen Institute for Neuroscience Leadership Chair, Howard Hughes Medical Institute Investigator, and director of the Tianqiao and Chrissy Chen Institute for Neuroscience. A paper describing the research appears online in the journal Neuron on November 8.

"Threat displays are virtually universal in the animal kingdom but we have known virtually nothing about how they are controlled by the brain," says Anderson. "Human observers can tell the difference between threat behavior and contact aggression; the question is whether the brain also 'knows the difference'—meaning, whether there are separate brain centers controlling threat displays versus actual fighting, or whether threats versus contact aggression just reflect weaker versus stronger activation of some kind of generic aggression circuit. To use a radio analogy, is it just turning up the volume on the same station, or switching between different stations?"

For the first time, Duistermars and his colleagues were able to definitively characterize the elemental movements of a fly's threat display: rapid, short charges forward; continual reorientation toward the opponent; and wings thrown out to the side and upward to make the fly look larger. Using this quantitative description of threats, the team identified a small cluster of three neurons, called the threat module, which generates this complex threatening behavior.

Once they had identified this neural threat module, the researchers genetically modified the cluster of neurons to enable their artificial stimulation or silencing. Normally, flies exhibit a threat display only when they detect another male fly's pheromones and see that fly move. However, artificial activation of the threat module caused the flies to exhibit a threat display without any actual targets in their environment. The team found that a low amount of activation initiated the fly's quick charges and reorientation behaviors; a higher amount of activation added the wing movements. 

"There are different intensities of aggression, from mild to wild threat displays, and from threats to actual physical violence," says Duistermars. "We want to know how animal nervous systems generate this kind of escalation in aggressive expressions."

The group found that stimulating the threat module was only sufficient to induce threats, but not to initiate a physical attack. But when the neurons were inhibited, the flies would progress straight to attacking without exhibiting any threats. This could imply that threat behaviors and attacking behaviors are controlled by separate neurons.

The next step for the team is to examine the rest of this so-called neural circuit: the neurons that are upstream and downstream of the threat module.

"We speculate that these threat neurons are integrating multiple sensory inputs, like male pheromonal cues and visual motion, and transforming them into complex motor output," says Duistermars. "To build on this work, we want to know how peripheral sensory circuits activate threat neurons and, in turn, how threat neurons activate the circuits that generate threatening movements."

"Humans display threats in a manner similar to flies, so we might have a similar set of neurons in our own brains that generate these expressions," he adds. "This work is an important advance in understanding how animal brains coordinate complex social behaviors. In this sense, I really see the study of flies as continuous with the study of ourselves."

The paper is titled, "A brain module for scalable control of complex, multi-motor threat displays." In addition to Duistermars and Anderson, other co-authors are Caltech staff scientist Eric Hoopfer and Barret Pfeiffer of the Howard Hughes Medical Institute. Funding was provided by the Ellison Medical Foundation and the Howard Hughes Medical Institute.

Related Links: How Social Isolation Transforms the BrainNature or Nurture? Innate Social Behaviors in the Mouse BrainEmotions in the Brain: An Interview with David Anderson
Thu, 08 Nov 2018
1922-2018 News Writer: Lori Oliwenstein Walter Burke

Walter Burke, longtime president and treasurer of the Sherman Fairchild Foundation and a life member of the Caltech Board of Trustees, passed away on November 1, 2018. He was 96 years old.

First named to the Caltech Board of Trustees in 1975, Burke was elected a life member in 2009 and held this position until his death. He was a member of the Jet Propulsion Laboratory committee as well as a member of the visiting committees for the divisions of physics, mathematics and astronomy (PMA), and the humanities and social sciences (HSS).

In 2014, Caltech and the Sherman Fairchild Foundation honored Burke with the creation of the Walter Burke Institute for Theoretical Physics, which has strengthened Caltech's leading role in the quest to discover fundamental laws of nature and to explain natural phenomena at all scales—from subatomic, atomic, and molecular scales to the scales of celestial objects and the universe itself.

"Walter's leadership and longstanding participation on the board of trustees, as well as his generosity and commitment to advancing scientific understanding, have left an enduring legacy for us to honor and uphold," says David L. Lee (PhD '74), chairman of the Board of Trustees.

"Walter's storied career, taste for talent, and exemplary generosity contributed to Caltech's success for more than 40 years," says Caltech president Thomas Rosenbaum, the Sonja and William Davidow Presidential Chair and professor of physics. "He was a champion for our scholars and a catalyst for discovery, including the transformative detection of gravitational waves. He will continue to live in our memories and as part of the Institute's continuing impact on the world."

As the founding director of the Sherman Fairchild Foundation, Burke helped to establish a longstanding relationship between Caltech and the foundation. Among the efforts he was closely involved in were the creation of the Sherman Fairchild Distinguished Scholars Program, which brought hundreds of scientists and researchers to Caltech for extended visits from 1973 to 1994. The visitors who came to campus through this program have included Stephen Hawking and several Nobel laureates. Similarly, he was very supportive of a program that brought Hawking to Caltech annually for research collaborations and lectures between 1991 and 2013.

"Walter was a wonderful friend to me, to PMA, and to Caltech," says Kip Thorne (BS '62), Richard P. Feynman Professor of Theoretical Physics, Emeritus, and a 2017 Nobel Laureate in Physics. "He was a longtime member of the Caltech Board of Trustees and of the PMA visiting committee, where his frank, to-the-point advice was of great value."

Burke was an early supporter of Thorne's research group and, later, of the Caltech-Cornell SXS Program to simulate sources of gravitational waves. That program has been crucial to the black-hole discoveries made by the Laser Interferometer Gravitational-wave Observatory (LIGO).

"Walter made lasting contributions to theoretical physics and other areas of science at Caltech," adds Hirosi Ooguri, the director of the Burke Institute for Theoretical Physics and the Fred Kavli Professor of Theoretical Physics and Mathematics. "We miss him greatly."

Burke was born on July 30, 1922, in New York. He attended Dartmouth College from 1940 through 1942 and served as a lieutenant junior grade in the Naval Reserve from 1942 to 1946. After receiving his LLB from Columbia Law School in 1948, he practiced with Cadwalader, Wickersham & Taft from 1948 to 1952. He then became a financial adviser to Sherman Fairchild, the inventor of the aerial camera, and eventually succeeded him as chairman of the board of the Fairchild Camera and Instrument Corporation. Burke served on the board of the Sherman Fairchild Foundation for more than 50 years, including 35 years as president.

He was a life trustee of the Pierpont Morgan Library and Museum, and a trustee emeritus of the Metropolitan Museum of Art and of Columbia University. He was also a former trustee and board chairman of both Dartmouth College and the Brunswick School in Greenwich, Connecticut, of which he was an alumnus. He held an Honorary Doctor of Laws Degree from Dartmouth College.

Burke, who was preceded in death by his son Douglas Burke, is survived by his wife of 76 years, Constance Burke; children Diane Burke, Nancy Burke Tunney, Bonnie Burke Himmelman, and Walter F. Burke III; and other family.

Related Links: Walter Burke Institute for Theoretical Physics Established at Caltech
Wed, 07 Nov 2018