Two Caltech Faculty Inducted into the AAAS

Erik Winfree (PhD '98) and Jay R. Winkler (PhD '84) have been elected as Fellows of the American Association for the Advancement of Science (AAAS). Winfree, a professor of computer science, computation and neural systems, and bioengineering, was recognized by the AAAS for his "foundational contributions to biomolecular computing and molecular programming." Winkler is a faculty associate and lecturer in chemistry in the Division of Chemistry and Chemical Engineering, as well as the director of the Beckman Institute Laser Resource Center. He was elected for "distinguished contributions to the field of electron transfer chemistry and the development of its applications in biology, materials science, and solar energy."

Winfree's research with biological computing aims to "coax DNA into performing algorithmic tricks," he says. An algorithm is a collection of mechanistic rules—information—that directs the creation and organization of structure and behavior. In biology, information in DNA can be likened to an algorithm: it encodes instructions for biochemical networks, body plans, and brain architectures, and thus produces complex life. The Winfree group is developing molecular engineering methods that exploit the same principles as those used by biology: they study theoretical models of computation based on realistic molecular biochemistry, write software for molecular system design and analysis, and experimentally synthesize promising systems in the laboratory using DNA nanotechnology.

"We are seeking to create a kind of molecular programming language: a set of elementary components and methods for combining them into complex systems that involve self-assembled structures and dynamical behaviors," Winfree says. "DNA is capable of and can be rationally designed to perform a wide variety of tasks. We want to know if DNA is a sufficient building block for constructing arbitrarily complex and sophisticated molecular machines."

Winfree became an assistant professor at Caltech in 2000, an associate professor in 2006, and was named full professor in 2010. He was also named a MacArthur Fellow in 2000.

Winkler works on developing new methods for using laser spectroscopy to study chemical kinetics and the intermediate molecules that form during chemical reactions. In particular, his work involves experimental investigations of the factors that affect the rates of long-range electron-tunneling processes—the processes by which electrons are transported between atoms and molecules.

"Electron transfer reactions are fundamental processes in many chemical transformations, including electrochemical catalysis, solar energy conversion, and biological energy transduction," Winkler says. "In the Beckman Institute Laser Center, we have spent the past 25 years studying electron transfer reactions in small inorganic molecules and in metalloproteins"—proteins that contain metal atoms. "Our studies are aimed at experimentally elucidating the molecular factors that regulate the speed and efficiency of electron flow.

"I have been fortunate to work on these projects with many dedicated and talented students and postdoctoral scholars at Caltech. It is extremely gratifying to have this work recognized by the AAAS," he adds.

Following postdoctoral work at the Brookhaven National Laboratory, Winkler returned to Caltech as a Member of the Beckman Institute in 1990. He was first appointed as a lecturer in chemistry in 2002, and later a faculty associate in chemistry in 2008.

In addition to Winkler and Winfree, eight other Caltech alumni were named as AAAS Fellows: Edmund W. Bertschinger (BS '79), J. Edward Russo (BS '63), Mitchell Kronenberg (PhD '83), Donald P. Gaver III (BS '82), James W. Demmel II (BS '75), Jacqueline E. Dixon (PhD '92), Brian K. Lamb (PhD '78), and Shelly Sakiyama-Elbert (MS '98, PhD '00).

The AAAS is the world's largest general scientific society. This year, the AAAS awarded the distinction of Fellow to 347 of its members. New Fellows will be honored during the 2016 AAAS Annual Meeting in February.

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Viral Videos (and Bacterial Ones, Too)

Grant Jensen is a high-powered movie producer. You won't see his name on any of this fall's Hollywood blockbusters, but in the field of cell biology, he has revolutionized the view that researchers, and even the curious public, get of the insides of cells. He does this through the innovative use of a digital camera and specialized electron microscope, which together enable a field called cryo-electron microscopy, or cryo-EM.

Now, he's taking what he's learned over the past 13 years using cryo-EM and sharing it with the world through a series of online videos that serve as visual textbooks to teach to the world the skills and knowledge needed for cryo-EM studies.

Read the full story on the E&S website

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Grant Jensen has revolutionized the view that researchers, and even the curious public, get of the insides of cells.

Neurons Encoding Hand Shapes Identified in Human Brain

Neural prosthetic devices, which include small electrode arrays implanted in the brain, can allow paralyzed patients to control the movement of a robotic limb, whether that limb is attached to the individual or not. In May 2015, researchers at Caltech, USC, and Rancho Los Amigos National Rehabilitation Center reported the first successful clinical trial of such an implant in a part of the brain that translates intention—the goal to be accomplished through a movement (for example, "I want to reach to the water bottle for a drink")—into the smooth and fluid motions of a robotic limb. Now, the researchers, led by Richard Andersen, the James G. Boswell Professor of Neuroscience, report that individual neurons in that brain region, known as the posterior parietal cortex (PPC), encode entire hand shapes which can be used for grasping—as when shaking someone's hand—and hand shapes not directly related to grasping, such as the gestures people make when speaking.

Most neuroprostheses are implanted in the motor cortex, the part of the brain controlling limb motion. But the movement of these robotic arms are jerky, probably due to the complicated mechanics for controlling muscle movement. Having eliminated that problem by implanting the device in the PPC, the brain region that encodes the intent, led Andersen and colleagues to further investigate the role specific neurons play in this part of the brain.

The research appears in the November 18 issue of the Journal of Neuroscience.

"The human hand has the ability to do numerous complex operations beyond just grasping," says Christian Klaes, a postdoctoral fellow at Caltech and first author of the paper. "We gesture when we speak, we manipulate objects, we use sign language to communicate with the hearing impaired. Tetraplegic patients rate hand and arm function to be of the highest importance to have better control over their environment. So our ultimate goal is to improve the range of neuroprostheses using control signals from the PPC.

"The more precisely we can identify individual neurons involved with hand movements, the better the capability these robotic devices will provide. Ultimately, we hope to mimic in a robotic hand the same freedom of movement of the human hand."

In the study, the researchers used the rock-paper-scissors game and a variation, rock-paper-scissors-lizard-Spock. The game, says Andersen, is "perfect" for this kind of research. "The addition of a lizard, depicted as a cartoon image of a lizard, and Spock—a picture of Leonard Nimoy in character—was to increase the repertoire of possible hand shapes available to our tetraplegic participant, Erik G. Sorto, whose limbs are completely paralyzed. We assigned a pinch gesture for the lizard and a spherical shape for Mr. Spock."

The game was played in two phases, first rock-paper-scissors and then the expanded game with the lizard and Spock. In the task, Sorto was briefly shown an object on a screen that corresponded to one of the hand shapes—for example, a picture of a rock or Mr. Spock. The image was followed by a blank screen, and then text appeared instructing Sorto to imagine making the corresponding hand shape with his right hand—a fist for the rock, an open hand for paper, a scissors gesture for scissors, a pinch for the lizard, and a spherical shape (loosely analogous to the Vulcan salute) for Spock—and to say which visual image he had seen, as the neuroprosthetic device recorded the activity of neurons in the PPC.

The researchers were able to identify single neurons in the PPC that fired when Sorto was presented with an image of an object to be grasped—a rock, say—and identified a nearly completely separate class of neurons that responded when Sorto engaged in motor imagery (the mental planning and imagined execution of a movement without the subject actually trying to move the limb).

"We found two mostly separate populations of neurons in the PPC that show either visual responses or motor-imagery responses during the task, the former when Erik identified a cue and the latter when he imagined performing a corresponding hand shape," says Andersen.

The researchers discovered that individual neurons in the PPC also responded to hand shapes that did not directly correspond to a grasp-related visual stimulus. The paper shape can be related to the initial opening of the hand to grasp a paper, and the rock closing the hand to grasp a rock—and in fact, these imagined hand shapes were used by Sorto to imagine opening a robotic hand by imagining paper and closing the robotic hand around an object by imagining rock. However, scissors, lizard, and Spock call for imagining hand gestures that are more abstract and iconic than those needed to grasp the visual objects, and suggests, says Andersen, that this area of the brain may also be involved in more general hand gestures, such as ones we use when talking, or for sign language.

The results of the trial were published in a paper titled, "Hand Shape Representations in the Human Posterior Parietal Cortex." In addition to Andersen and Klaes, other authors on the study are Spencer Kellis, Tyson Aflalo, and Kelsie Pejsa from Caltech; Brian Lee, Christi Heck, and Charles Liu from USC; and Kathleen Shanfield, Stephanie Hayes-Jackson, and Mindy Aisen from Rancho Los Amigos National Rehabilitation Center.

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The neurons, identified through brain studies using the game rock-paper- scissors-lizard-Spock, may lead to improved prosthetic devices.

Choosing the T-Cell Profession: Higher Education for Stem Cells

Watson Lecture Preview

Your body is continuously making new blood cells from a reservoir of "starter" cells called stem cells. Blood cells come in many types, including the highly versatile T cells that play a number of key roles in the immune system. All stem cells are alike, and all the T cells that come from them start out alike before choosing specific careers in response to signals from their environment.

On Wednesday, November 18 at 8 p.m. in Caltech's Beckman Auditorium, Ellen Rothenberg, Caltech's Albert Billings Ruddock Professor of Biology, will lead us along the paths that T cells follow and show how her lab has mapped their journeys. Admission is free.

What do you do?

I'm interested in how cells choose their identities through reading out information stored in the genome, which is the entire collection of DNA that makes a creature what it is, and how a cell that begins with one identity can spawn descendants with very different, very durable new identities.

We study T cells, a large family of white blood cells that form a major part of your immune system. T cells have an extremely long and varied life. They come from so-called stem cells, which have the ability to become many, many different kinds of cells. We want to learn how a "blank slate" of a stem cell develops to achieve a rock-solid identity as a T cell—especially because a T cell has an irreversibly defined "T-cell-ness" at its core, yet it remains very dynamic in using genomic information to decide what kind of T cell it will be.

Generating T cells is a three-step process. First, a stem cell develops into a T cell. Second, the T cell circulates around the body, waiting to see how it will first be used by the body to fight an actual infection. And then third, once it has evolved a specialization, it will continue to go around the body for months, years, or even decades in humans, spawning descendants that are also specialized with the same specific type of cellular function the original T cell had when it was activated—as helper T cells, or killer T cells, or whatever other type of T cell was needed. And they may pick a subspecialty—for example, for every infectious agent you encounter, you develop a specific memory cell to recognize that particular bug so that if it comes around again you are ready for it.

Once made, the decisions are locked in. All the T cell's progeny will generally stay in "the family business." However, it sometimes happens that once a T cell has chosen its profession, a particularly strong environmental signal can drive it to change into a different type of T cell. But even so, it will never, ever go back to being a stem cell. My lab is trying to figure out the molecular control mechanisms that allow the former stem cell to achieve a new rock-solid identity as a T cell, yet maintain a level of flexibility within that T-cell-ness.

Why is this important?

I study biology for the same reason that astronomers study the universe. I believe that there are deep biological principles to be learned from T cells, whose import goes way beyond curing a particular disease. I'm ecstatic when things we do are picked up by clinicians, who do make a profession of helping people, but I do basic science.

There are two main branches to the developmental biology of multicellular organisms. The first goes from the fertilized egg through the embryo, and that's the process that makes your body in the first place. It follows well-known rules worked out by people like my late colleague Eric Davidson [Caltech's Norman Chandler Professor of Cell Biology].

I study a second form of development that begins when an embryo sets aside a bunch of cells and programs them to become stem cells. Stem cells do not differentiate further right away; they just make more copies of themselves. Then, whenever you need to make new blood cells or repair a tissue later in life, those cells are called into action. For example, red blood cells only last about three or four months, so the blood circulating in your body today is coming from stem cells, and those stem cells were "set aside" when you were a fetus. This means there's an additional set of rules, going well beyond embryonic development, for making new blood cells in the right balance and at the right time.

The new cells do have some wear and tear from the consequences of your adventures throughout your life, but to a first approximation they're the same. They're getting primed to do the same job. They have to set up all the molecular circuitry needed to retain their identity and maintain a clear one-directional flow from stem-ness to differentiation. The process has to be as accurate at our advanced ages as it was when we were fetuses. That's the genius of stem-cell-based developmental biology. In my view, the collection of stem-cell development mechanisms ranks right up there with the more established mechanisms of embryonic development.

How did you get into this line of work?

I've always been interested in science. The question when I was young was whether I wanted to be a physicist or a biologist, but then I fell completely in love with biochemistry when I was in high school. When I went off to Harvard I didn't know specifically what I was interested in, but I loved what was known about the genome. I thought it would be fantastic to understand how the genome works at a molecular, mechanistic level.

I had the great good fortune to have microbiologist Boris Magasanik as my undergraduate tutor and mentor. He was the head of MIT's biology department, but he had a relationship with Harvard and he liked teaching undergrads. Boris was an extraordinary intellectual. He was studying metabolic pathways in bacteria at the systems-biology level way before it was normal. He was drawing prototype diagrams of gene-regulatory networks back in the early '70s.

A lot of technology had to be invented before we could explain gene regulation on the molecular level, but when I became a graduate student in [Nobel Laureate] David Baltimore's lab at MIT in 1972, he was already doing incredible work on viral genomes. [Baltimore came to Caltech in 1997 and is currently the Robert Andrews Millikan Professor of Biology.] We were pushing the frontiers of knowledge outward on a daily basis, and it was exceptionally exciting.

However, the development of multicelled organisms was still extremely hard to understand back then. It seemed all anecdotal, as if every organism did things in a fundamentally different way. But by the late '70s, Eric Davidson here at Caltech was making it possible to make sense out of developmental systems. His views integrated Boris Magasanik's systems-level view with David Baltimore's molecular-level finesse, and his work was revealing general mechanisms of development in multicellular organisms. I owe a great deal to the conceptual and mechanistic perspectives that I have gotten from these three people.

Also, Caltech's smallness has been fantastic. Most of the people I know who work with T cells are in immunology departments, and most immunologists do the same kinds of things, more or less. The joy for me at Caltech has been doing things that nobody else is doing. Often when my colleagues here solve their problems, I can use those approaches to break new ground in my field. It's been extraordinarily fun, and a tremendous advantage. Science as it should be done.

Long ago at MIT, my labmates and I were studying a retrovirus that caused early T-cell leukemia in mice. Lots of retroviruses cause cancer by putting a gene responsible for normal cell growth into the host cell and then turning the gene on under the wrong conditions. But our retrovirus didn't cause cancer in other cell types, so we wondered why it affected early T cells. I realized that the T-cell development process itself must be an especially sensitive target. The retrovirus nudged the future T cells toward being cancerous, possibly by accident, and then a little push farther down the line would send them over the edge.

That's when I became interested in T-cell development and this question of what controlled the switchover between growth and differentiation. We've found in the last 10 years or so that there are actually two bursts of proliferation during T-cell development. My lab has focused on the first one, which we now know is the transition between stem-cell-ness and T-cell-ness, when the cell commits to becoming a T cell. And it turns out that if a stem-cell regulatory gene stays on during the process, you get an abnormal persistence of stem-cell-like growth and sometimes leukemia. It's ironic that it's taken me, gosh, 40 years to get back to that, but it has been an incredibly satisfying journey.

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T Cells Get Schooled
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The road to becoming a T cell is fraught with choices, false starts, and dead ends, where a regulatory tug-of-war brings cells close to the border of leukemia.

Yuki Oka Awarded Mallinckrodt Grant

Yuki Oka, an assistant professor of biology, has been awarded a grant from the Edward Mallinckrodt, Jr. Foundation, given to "support early stage investigators engaged in biomedical research that has the potential to significantly advance the understanding, diagnosis, or treatment of disease," according to the foundation website. The grant will provide $60,000 per year for three years.

"I'm thrilled by being selected for the 2015 Mallinckrodt Grant," says Oka, whose lab uses thirst and water-drinking behavior as a simple model system to study how the brain monitors internal water balance and generates signals that drive appetitive behaviors. The long-term goal of the work is to understand how the brain integrates information about the internal body state and external sensory information to maintain homeostasis (a state of internal equilibrium). The research, he notes, will provide a framework for studying the mechanisms that govern innate behaviors such as eating and drinking. Currently, an estimated 30 million people in the U.S. suffer from appetite disorders including polydipsia and bulimia, characterized by excessive water and food intake, respectively. Identifying neural circuits underlying appetite may offer insights into safe treatments for associated disorders, he says.

Oka received his PhD from the University of Tokyo and was a postdoctoral researcher at UC San Diego and Columbia University before joining the Caltech faculty in 2014. He was named a Searle Scholar in April 2015.

Past Mallinckrodt grantees from Caltech include Sarkis Mazmanian, the Luis B. and Nelly Soux Professor of Microbiology; David Prober, assistant professor of biology; Mitchell Guttman, assistant professor of biology; and Viviana Gradinaru, assistant professor of biology and biological engineering.

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Yuki Oka, an assistant professor of biology, has been awarded a grant from the Edward Mallinckrodt, Jr. Foundation.

When Harry Met Arnold

A Milestone in Chemistry

On November 12 and 13, the Beckman Institute at Caltech hosted a symposium on "The Shared Legacy of Arnold Beckman and Harry Gray." The two began a close working relationship in the late 1960s, when Gray arrived at Caltech. In this interview, Gray provides some background.

How did you come to Caltech?

I grew up in southern Kentucky. I got my BS in chemistry in 1957, and my professors told me to go to grad school at Northwestern University in Evanston, Illinois, to continue my studies in synthetic organic chemistry. They didn't give me a choice. Western Kentucky College had physical chemistry, analytical chemistry, organic chemistry, and that was it.

When I got to Northwestern I met Fred Basolo, who became my mentor. He did inorganic chemistry, which I was very surprised to discover even existed as a research field. I was so excited by his work, which was studying the mechanisms of inorganic reactions, that I decided to switch fields and do what he did. I got my PhD in 1960 from work on the syntheses and reaction mechanisms of platinum, rhodium, palladium, and nickel complexes. A complex has a metal atom sitting in the middle of as many as six ions or molecules called ligands. The metal has empty orbitals that it wants to fill with paired-up electrons, and the ligands have electron pairs they aren't using, so the metal and its ligands form stable bonds.

I had gotten into chemistry in the first place because I'd always been interested in colors. Even when I was a little kid, colors fascinated me. I really wanted to understand them, and many complexes have brilliant, beautiful colors. At Northwestern I heard about crystal-field theory, which was the first attempt to explain how metal complexes got their colors. All the crystal-field theory's big shots were in Copenhagen, so I decided to go there as a postdoc. Which I did.

I soon found out that crystal-field theory didn't go far enough. It only explained the colors of a limited set of metal ions in solution, and it couldn't explain charge transfers and a lot of other things. All the atoms were treated as point charges, with no provision for the bonds between the metal and the ligands. There weren't any bonds. So I helped develop a new theory, called ligand-field theory, which put the bonds back in the complexes. Carl Ballhausen, a professor at the University of Copenhagen, and I wrote a paper on a "metal-oxo" complex in which an oxygen atom was triple-bonded to a vanadium ion. The triple bond in our theory was required to account for the blue color of the vanadium-oxo complex. We also could explain charge transfers in other oxo complexes. Bonds were back in metal complexes!

Metal-oxo bonds are very important in biology. They are crucial in a lot of reactions, such as the oxygen-producing side of photosynthesis; the metabolism of drugs by cytochrome P-450, which often leads to toxic interactions with other drugs; and respiration. When we breathe in O2, our respiratory system splits the O=O bond, forming a metal-oxo complex as a reactive intermediate on the way to the product, which is water.

My work on bonding in metal oxo complexes got me a job as an assistant professor at Columbia University in 1961. By '65 I was a full professor and getting offers from many places, including Caltech. I loved Columbia, and I would have stayed there, but the chemistry department was very small. I knew it would be hard to build inorganic chemistry in a small department that concentrated on organic and physical chemistry.

There weren't any inorganic chemists at Caltech, either, but division chair Jack Roberts encouraged me to build the field up to five or six faculty members. I came to Caltech in 1966, and we now have a very strong inorganic chemistry group.

When I got here, I started work in two new areas at the interface of inorganic chemistry and biology. I'm best known for my work showing how electrons flow through proteins in respiration and photosynthesis. I won the Wolf Prize and the Welch Prize and the National Medal of Science for this work.

I also got into inorganic photochemistry—solar-energy research. That work started well before the first energy crisis in 1973, and continued until oil became cheap again in the early 1980s and solar-energy research was no longer supported. In the late '90s, I restarted the work. Now I'm leading an NSF Center for Chemical Innovation in Solar Fuels, which has an outreach activity I proudly call the Solar Army.

And how's that going?

The Solar Army keeps growing. We now have at least 60 brigades at high schools across the U.S., and 10 more abroad. I'd say that about 1,000 students have been through the program since 2008. We're getting young scientists involved in research that could have a profound effect on the world they're going to inherit. They're helping us look for light absorbers and catalysts to turn water into hydrogen fuel, using nothing but sunlight. The solar materials need to be sturdy metal oxides that are abundant and dirt cheap. But there are many metals in the periodic table. When you start combining them in twos and threes in varying amounts, there are literally millions of possibilities to be tested. We already have found several very good water oxidation and reduction catalysts, and since the National Science Foundation has just renewed our CCI Solar Fuels grant, we expect to make great progress in the coming years in understanding how they work.

Let's shift gears and talk about the Beckman Institute. How did you first meet Arnold Beckman [PhD '28, inventor of the pH meter, founder of Beckman Instruments, and a Life Trustee of Caltech]?

I gave a talk back in 1967, probably on Alumni Day. Arnold was the chair of Caltech's Board of Trustees at the time, and he and his wife, Mabel, were seated in the second row. When the talk was over, they came down and introduced themselves. Mabel said—and I remember this very well—she said, "Arnold, I didn't understand much of what this young man said, but I really liked the way he said it." Arnold gave me the thumbs up, and that started our relationship.

When I became chairman of the Division of Chemistry and Chemical Engineering in 1978, I asked him to be on my advisory committee. I didn't ask him for money, but I asked him for advice, and we became quite close. He said he wanted to do something for us. That led to his gift for the Arnold and Mabel Beckman Laboratory of Chemical Synthesis, as well as a gift for instrumentation.

He liked it that we raised money to match his instrument gift. He told me that he wanted to do something bigger, so we started thinking about building the Beckman Institute. [Caltech President] Murph Goldberger and I would go down to Orange County about every week with a new plan. He rejected the first four or five until we came up with the idea of developing technology to support chemistry and biology—methods and instruments for fundamental research—and creating resource centers to house them.

Once we agreed on what the building should house, we started planning the building itself. But when we showed Arnold our design, which was four stories plus a basement, he said, "That's not big enough. You need another floor for growth." So we added a subbasement that was quickly occupied by a resource center for magnetic-resonance imaging and optical imaging that has been heavily used by biologists, chemists, and other investigators.

The Beckman Institute has done a lot over the last 25 years. But it develops technology for general research use, so it doesn't often make the headlines itself. Are you OK with that?

Many advances in science and technology have been made in the Beckman Institute over the last 25 years. The methods and instruments that have been developed in BI resource centers have made enormous impacts at the frontiers of chemistry and biology. Solar-fuels science and human biology are just two examples of areas where work in the Beckman Institute has made a big difference. And there are many more. Am I proud? You bet I am!

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When Harry Met Arnold
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Caltech celebrates the 25th year of the Beckman Institute and the 80th birthday of Harry Gray, the Beckman Professor of Chemistry and the founding director of the institute.
Monday, November 30, 2015

Microbial diners, drive-ins, and dives: deep-sea edition

Elachi to Retire as JPL Director

Charles Elachi (MS '69, PhD '71) has announced his intention to retire as director of the Jet Propulsion Laboratory on June 30, 2016, and move to campus as professor emeritus. A national search is underway to identify his successor.

"A frequently consulted national and international expert on space science, Charles is known for his broad expertise, boundless energy, conceptual acuity, and deep devotion to JPL, campus, and NASA," said Caltech president Thomas F. Rosenbaum in a statement to the Caltech community. "Over the course of his 45-year career at JPL, Charles has tirelessly pursued new opportunities, enhanced the Laboratory, and demonstrated expert and nimble leadership. Under Charles' leadership over the last 15 years, JPL has become a prized performer in the NASA system and is widely regarded as a model for conceiving and implementing robotic space science missions."

With Elachi at JPL's helm, an array of missions has provided new understanding of our planet, our moon, our sun, our solar system, and the larger universe. The GRAIL mission mapped the moon's gravity; the Genesis space probe returned to Earth samples of the solar wind; Deep Impact intentionally collided with a comet; Dawn pioneered the use of ion propulsion to visit the asteroids Ceres and Vesta; and Voyager became the first human-made object to reach interstellar space. A suite of missions to Mars, from orbiters to the rovers Spirit, Opportunity, and Curiosity, has provided exquisite detail of the red planet; Cassini continues its exploration of Saturn and its moons; and the Juno spacecraft, en route to a July 2016 rendezvous, promises to provide new insights about Jupiter. Missions such as the Galaxy Evolution Explorer, the Spitzer Space Telescope, Kepler, WISE, and NuSTAR have revolutionized our understanding of our place in the universe.

Future JPL missions developed under Elachi's guidance include Mars 2020, Europa Clipper, the Asteroid Redirect Mission, Jason 3, Aquarius, OCO-2, SWOT, and NISAR.

Elachi joined JPL in 1970 as a student intern and was appointed director and Caltech vice president in 2001. During his more than four decades at JPL, he led a team that pioneered the use of space-based radar imaging of the Earth and the planets, served as principal investigator on a number of NASA-sponsored studies and flight projects, authored more than 230 publications in the fields of active microwave remote sensing and electromagnetic theory, received several patents, and became the director for space and earth science missions and instruments. At Caltech, he taught a course on the physics of remote sensing for nearly 20 years

Born in Lebanon, Elachi received his B.Sc. ('68) in physics from University of Grenoble, France and the Dipl. Ing. ('68) in engineering from the Polytechnic Institute, Grenoble. In addition to his MS and PhD degrees in electrical science from Caltech, he also holds an MBA from the University of Southern California and a master's degree in geology from UCLA.

Elachi was elected to the National Academy of Engineering in 1989 and is the recipient of numerous other awards including an honorary doctorate from the American University of Beirut (2013), the National Academy of Engineering Arthur M. Bueche Award (2011), the Chevalier de la Légion d'Honneur from the French Republic (2011), the American Institute of Aeronautics and Astronautics Carl Sagan Award (2011), the Royal Society of London Massey Award (2006), the Lebanon Order of Cedars (2006 and 2012), the International von Kármán Wings Award (2007), the American Astronautical Society Space Flight Award (2005), the NASA Outstanding Leadership Medal (2004, 2002, 1994), and the NASA Distinguished Service Medal (1999).

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He will move to campus as professor emeritus. A national search is underway to identify his successor.

Seeing Sound

A busy kitchen is a place where all of the senses are on high alert—your brain is processing the sound of sizzling oil, the aroma of spices, the visual aesthetic of food arranged on a plate, the feel and taste of taking a bite. While these signals may seem distinct and independent, they actually interact and integrate together within the brain's network of sensory neurons.

Caltech researchers have now discovered that intrinsic neural connections—called crossmodal mappings—can be used by assistive devices to help the blind detect their environment without requiring intense concentration or hundreds of hours of training. This new multisensory perspective on such aids (called sensory substitution devices) could make tasks that were previously attention-consuming much easier, allowing nonsighted people to acquire a new sensory functionality similar to vision. The work is described in a paper published in the October 22 issue of the journal Scientific Reports.

"Many neuroscience textbooks really only devote a few pages to multisensory interaction," says Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology and principal investigator on the study. "But 99 percent of our daily life depends on multisensory—also called multimodal—processing." As an example, he says, if you are talking on the phone with someone you know very well, and they are crying, you will not just hear the sound but will visualize their face in tears. "This is an example of the way sensory causality is not unidirectional—vision can influence sound, and sound can influence vision."

Shimojo and postdoctoral scholar Noelle Stiles have exploited these crossmodal mappings to stimulate the visual cortex with auditory signals that encode information about the environment. They explain that crossmodal mappings are ubiquitous; everyone already has them. Mappings include the intuitive matching of high pitch to elevated locations in space or the matching of noisy sounds with bright lights. Multimodal processing, like these mappings, may be the key to making sensory substitution devices more automatic.

The researchers conducted trials with both sighted and blind people using a sensory substitution device, called a vOICe device, that translates images into sound.

The vOICe device is made up of a small computer connected to a camera that is attached to darkened glasses, allowing it to "see" what a human eye would. A computer algorithm scans each camera image from left to right, and for every column of pixels, generates an associated sound with a frequency and volume that depends upon the vertical location and brightness of the pixels. A large number of bright pixels at the top of a column would translate into a loud, high-frequency sound, whereas a large number of lower dark pixels would be a quieter, lower-pitched sound. A blind person wearing this camera on a pair of glasses could then associate different sounds with features of their environment.

In the trials, sighted people with no training or instruction were asked to match images to sounds; while the blind subjects were asked to feel textures and match them to sound. Tactile textures can be related to visual textures (patterns) like a topographic map—bright regions of an image translate to high tactile height relative to a page, while dark regions are flatter. Both groups showed an intuitive ability to identify textures and images from their associated sounds. Surprisingly, the untrained (also called "naive") group's performance was significantly above chance, and not very different from the trained.

The intuitively identified textures used in the experiments exploited the crossmodal mappings already within the vOICe encoding algorithm. "When we reverse the crossmodal mappings in the vOICe auditory-to-visual translation, the naive performance significantly decreased, showing that the mappings are important to the intuitive interpretation of the sound," explains Stiles.

"We found that using this device to look at textures—patterns of light and dark—illustrated 'intuitive' neural connections between textures and sounds, implying that there is some preexisting crossmodality," says Shimojo. One common example of crossmodality is a condition called synesthesia, in which the activation of one sense leads to a different involuntary sensory experience, such as seeing a certain color when hearing a specific sound. "Now, we have discovered that crossmodal connections, preexisting in everyone, can be used to make sensory substitution intuitive with no instruction or training."

The researchers do not exactly know yet what each sensory region of the brain is doing when processing these various signals, but they have a rough idea. "Auditory regions are activated upon hearing sound, as are the visual regions, which we think will process the sound for its spatial qualities and elements. The visual part of the brain, when processing images, maps objects to spatial location, fitting them together like a puzzle piece," Stiles says. To learn more about how the crossmodal processing happens in the brain, the group is currently using functional magnetic resonance imaging (fMRI) data to analyze the crossmodal neural network.

These preexisting neural connections provide an important starting point for training visually impaired people to use devices that will help them see. A sighted person simply has to open their eyes, and the brain automatically processes images and information for seamless interaction with the environment. Current devices for the blind and visually impaired are not so automatic or intuitive to use, generally requiring a user's full concentration and attention to interpret information about the environment. The Shimojo lab's new finding on the role of multimodal processing and crossmodal mappings starts to address this issue.

Beyond its practical implications, Shimojo says, the research raises an important philosophical question: What is seeing?

"It seems like such an obvious question, but it gets complicated," says Shimojo. "Is seeing what happens when you open your eyes? No, because opening your eyes is not enough if the retina [the light-sensitive layer of tissue in the eye] is damaged. Is it when your visual cortex is activated? But our research has shown that the visual cortex can be activated by sound, indicating that we don't really need our eyes to see. It's very profound—we're trying to give blind people a visual experience through other senses."

The paper is titled "Auditory Sensory Substitution Is Intuitive and Automatic with Texture Stimuli" and was funded by grants from the National Science Foundation, the Della Martin Fund for Discoveries in Mental Illness, and the Japan Science and Technology Agency, Core Research for Evolutional Science and Technology.

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Intrinsic neural connections can be used by assistive devices, allowing non-sighted people to acquire a new sensory functionality similar to vision.
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Probing the Mysterious Perceptual World of Autism

New research looks at what people with Autism Spectrum Disorder pay attention to in the real world.

The perceptual world of a person with autism spectrum disorder (ASD) is unique. Beginning in infancy, people who have ASD observe and interpret images and social cues differently than others. Caltech researchers now have new insight into just how this occurs, research that eventually may help doctors diagnose, and more effectively treat, the various forms of the disorder. The work is detailed in a study published in the October 22 issue of the journal Neuron.

Symptoms of ASD include impaired social interaction, compromised communication skills, restricted interests, and repetitive behaviors. Research suggests that some of these behaviors are influenced by how an individual with ASD senses, attends to, and perceives the world.

The new study investigated how visual input is interpreted in the brain of someone with ASD. In particular, it examined the validity of long-standing assumptions about the condition, including the belief that those with ASD often miss facial cues, contributing to their inability to respond appropriately in social situations.

"Among other findings, our work shows that the story is not as simple as saying 'people with ASD don't look normally at faces.' They don't look at most things in a typical way," says Ralph Adolphs, the Bren Professor of Psychology and Neuroscience and professor of biology, in whose lab the study was done. Indeed, the researchers found that people with ASD attend more to nonsocial images, to simple edges and patterns in those images, than to the faces of people.

To reach these determinations, Adolphs and his lab teamed up with Qi Zhao, an assistant professor of electrical and computer engineering at the National University of Singapore, the senior author on the paper, who had developed a detailed method. The researchers showed 700 images to 39 subjects. Twenty of the subjects were high-functioning individuals with ASD, and 19 were control, or "neurotypical," subjects without ASD. The two groups were matched for age, race, gender, educational level, and IQ. Each subject viewed each image for three seconds while an eye-tracking device recorded their attention patterns on objects depicted in the images.

Unlike the abstract representations of single objects or faces that have been commonly used in such studies, the images that Adolphs and his team presented contained combinations of more than 5,500 real-world elements—common objects like people, trees, and furniture as well as less common items like knives and flames—in natural settings, mimicking the scenes that a person might observe in day-to-day life.

"Complex images of natural scenes were a big part of this unique approach," says first-author Shuo Wang (PhD '14), a postdoctoral fellow at Caltech. The images were shown to subjects in a rich semantic context, "which simply means showing a scene that makes sense," he explains. "I could make an equally complex scene with Photoshop by combining some random objects such as a beach ball, a hamburger, a Frisbee, a forest, and a plane, but that grouping of objects doesn't have a meaning—there is no story demonstrated. Having objects that are related in a natural way and that show something meaningful provides the semantic context. It is a real-world approach."

In addition to validating previous studies that showed, for example, that individuals with ASD are less drawn to faces than control subjects, the new study found that these subjects were strongly attracted to the center of images, regardless of the content placed there. Similarly, they tended to focus their gaze on objects that stood out—for example, due to differences in color and contrast—rather than on faces. Take, for example, one image from the study showing two people talking with one facing the camera and the other facing away so that only the back of their head is visible. Control subjects concentrated on the visible face, whereas ASD subjects attended equally to the face and the back of the other person's head.

"The study is probably most useful for informing diagnosis," Adolphs says. "Autism is many things. Our study is one initial step in trying to discover what kinds of different autisms there actually are. The next step is to see if all people with ASD show the kind of pattern we found. There are probably differences between individual people with ASD, and those differences could relate to differences in diagnosis, for instance, revealing subtypes of autism. Once we have identified those subtypes, we can begin to ask if different kinds of treatment might be best for each kind of subtype."

Adolphs plans to continue this type of research using functional magnetic resonance imaging scans to track the brain activity of people with ASD while they are viewing images in laboratory settings similar to what was used in this study.

The paper, "Atypical Visual Saliency in Autism Spectrum Disorder Quantified through Model-Based Eye Tracking," was coauthored by Shuo Wang and Ralph Adolphs at Caltech; Ming Jiang and Qi Zhao from the National University of Singapore; Xavier Morin Duchesne and Daniel P. Kennedy of Indiana University, Bloomington; and Elizabeth A. Laugeson from UCLA.

The research was supported by a postdoctoral fellowship from the Autism Science Foundation, a Fonds de Recherche du Québec en Nature et Technologies predoctoral fellowship, a National Institutes of Health Grant and National Alliance for Research on Schizophrenia and Depression Young Investigator Grant, a grant from the National Institute of Mental Health to the Caltech Conte Center for the Neurobiology of Social Decision Making, a grant from the Simons Foundation Autism Research Initiative, and Singapore's Defense Innovative Research Program and the Singapore Ministry of Education's Academic Research Fund Tier 2.

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Patterns of Attention of People with Autism Spectrum Disorder (ASD).
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New research into autism, utilizing complex real-world images, provides enhanced understanding of how people with autism attend to visual cues.

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