Spring Break in the Galápagos

 

As the final element of Evolution, Caltech's new Bi/Ge 105 course, a dozen students spent their spring break snorkeling with penguins and sharks, hiking a volcano, and otherwise taking in the natural laboratory for evolution that is the Galápagos Islands. The second-term course was created and is taught by Rob Phillips, the Fred and Nancy Morris Professor of Biophysics and Biology, and Victoria Orphan, professor of geobiology, and is designed to give students both a broad picture of evolution and a chance to make their own up-close-and-personal observations.

"Rob and I both feel very strongly that lab and field experiences are essential for the growth of the students as scientists," Orphan says. "Being at a place like Caltech that's small and where you have a lot of talented and enthusiastic students is the perfect environment to create those kinds of opportunities."

So with their trusty mascot—a bobblehead Darwin—in tow, the undergraduate students, their teaching assistant, and the two professors flew to Ecuador and then to the archipelago off the coast to spend a week living as field researchers and learning from Ecuadorian naturalist Ernesto Vaca and from their natural surroundings.

"The Galápagos are completely iconic," says Phillips. "Right before your eyes you can see the products of evolution, if you like. You can swim in the water with the flightless cormorants. The famed Darwin's finches are there. You can wonder what penguins are doing at the equator. What especially impresses me about seeing species such as the cormorants is the way they teach us about some of the most important evolutionary features seen on islands, such as dwarfism, gigantism, and flightlessness."

During the trip, each student made a presentation to the group, discussing a species or topic specific to the islands. One spoke about the Galápagos fur seal; another presented about the opuntia, a variety of cactus; another about marine iguanas. Senior bioengineering major Laura Santoso spoke about invasive species on the island. She says that although she had researched the subject extensively ahead of time, she saw things differently once she was actually in the Galápagos. For example, she had read that a particular invasive insect had been essentially eradicated from the islands, but while there she actually saw a number of the bugs. "It drove home how challenging it is to get rid of these invasive species," she says. "I find that observing the complexity of the issue in person and developing my own inferences makes it more meaningful."

Junior bioengineering major Aleena Patel agrees, adding that the trip suggested new ways to ask questions, to study, and to explore. "Being there in person piques curiosity in ways that other facets of learning don't," she says. "At times, there was so much to see it was almost overwhelming. But as scientists, we need that inspiration to ask questions and to be emotionally motivated."

That is just the kind of motivation Phillips and Orphan hoped to impart. "My view is that the most important point is to get students to plug into the idea of looking at nature and wondering, 'Why is that like that? How could science attack that question?' It's not so much a course about learning what is," says Phillips. "It's a course about saying, 'I wonder . . .'"

In addition to the Galápagos trip, the class took smaller day trips closer to campus during the winter term. On a special behind-the-scenes tour of the Page Museum at the La Brea Tar Pits, they were able to collect samples from one of the current excavations in order to study the microbes that make a living in such a unique environment. They also visited the Moore Lab of Zoology at Occidental College, where they used calipers to measure beaks in one of the world's largest collections of Mexican birds. The goal of the exercise was to get a feel for the kinds of measurements that biologists have conducted on finches on Daphne Major, one of the islands of the Galápagos, to study evolution in action.

The new class was supported by Caltech's Innovation in Education Fund, the Division of Geological and Planetary Sciences, and the Division of Biology and Biological Engineering through its William K. Bowes Jr. Leadership fund. As for why its focus was evolution, Orphan explains, "Evolution is of course integral to anyone doing biology. But when you start to look around, you find that evolution has its tendrils in a lot of different areas of research beyond biological research—even in computer science. We wanted to give the students that perspective, that even if they weren't going to be evolutionary biologists, per se, that the concepts and the way of perceiving the world in this class were going to help them."

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Spring Break in the Galapagos
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Unlocking a Mystery of Human Disease . . . in Space

An experiment just launched into orbit by a team of Caltech researchers could be an important step toward understanding a devastating neurodegenerative disease.

Huntington's disease is a grim diagnosis. A hereditary disorder with debilitating physical and cognitive symptoms, the disease usually robs adult patients of their ability to walk, balance, and speak. More than 15 years ago, researchers revealed the disorder's likely cause—an abnormal version of the protein huntingtin; however, the mutant protein's mechanism is poorly understood, and the disease remains untreatable.

Now, a new project led by Pamela Bjorkman, Max Delbrück Professor of Biology, will investigate whether the huntingtin protein can form crystals in microgravity aboard the International Space Station (ISS)—crystals that are crucial for understanding the molecular structure of the protein. The experiment was launched from Cape Canaveral in Florida on Friday, April 18 aboard the SpaceX CRS-3 cargo resupply mission to the ISS. On Sunday, April 20 the station's robotic arm captured the mission's payload, which included the proteins for Bjorkman's experiment—which is the first Caltech experiment to take place aboard the ISS.

In the experiment, the researchers hope to grow a crystal of the huntingtin protein—the crystal would be an organized, latticelike arrangement of the protein's molecules—which is needed to determine the molecular structure of the protein. However, molecules of the huntingtin protein tend to aggregate, or clump together, in Earth's gravity. And this disordered arrangement makes it incredibly hard to parse the protein's structure, says Gwen Owens, a graduate student in Bjorkman's lab and a researcher who helped design the study.

"We need crystals for X-ray crystallography, the technique we use to study the protein, in which we shoot an X-ray through the protein crystal and analyze the organized pattern of radiation that scatters off of it," Owens says. "That pattern is what we depend on to identify the location of every carbon, nitrogen, and sulfur atom within the protein; if we shoot an X-ray beam at a clumped, aggregate protein—like huntingtin often is—we can't get any data from it," she says.

Researchers have previously studied small fragments of crystallized huntingtin, but because of its large size and propensity to clumping, no one has ever successfully grown a crystal of the full-length protein large enough to analyze with X-ray crystallography. To understand what the protein does—and how defects in it lead to the symptoms of Huntington's disease—the researchers need to study the full-length protein.

Looking for a solution to this problem, Owens was inspired by a few previous studies of protein formation on space shuttles and the ISS—studies suggesting that proteins can form crystals more readily in a condition of near-weightlessness called microgravity. "The previous studies looked at much simpler proteins, but we thought we could make a pretty good case that huntingtin would be an excellent candidate to study on the ISS," Owens says.

They proposed such an experiment to the Center for the Advancement of Science in Space (CASIS), which manages U.S. research on the ISS, and it was accepted, becoming part of the first Advancing Research Knowledge, or ARK1, mission.

Because Owens and Bjorkman cannot travel with their proteins, and staff and resources are limited aboard the ISS, the crystal will be grown with a Handheld High-Density Protein Crystal Growth device—an apparatus that will allow astronauts to initiate growth of normal and mutant huntingtin protein crystals from a solution of protein molecules with just the flip of a switch.

As the crystals grow larger over a period of several months, samples will come back to Earth via the SpaceX CRS-4 return mission. The results of the experiment are scheduled to drop into the ocean just off the coast of Southern California—along with the rest of the return cargo—sometime this fall. At that point, Owens will finally be able to analyze the proteins.

"Our ideal result would be to have large crystals of the normal and mutant huntingtin proteins right away—on the first try," she says. After analyzing crystals of the full-length protein with X-ray crystallography, the researchers could finally determine huntingtin's structure—information that will be crucial to developing treatments for Huntington's disease.

Owens, a joint MD/PhD student at Caltech and UCLA's David Geffen School of Medicine, has also had the opportunity to work with Huntington's disease patients in the clinic, adding a human connection to her experiment in the sky. "The patients and families I have met who are affected by Huntington's disease are excited to see something big like this. It's inspiring for them—and hopefully it will inspire new research, too."

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Experiences from two years of MOOCs at Caltech: A WEST Public Seminar

John Dabiri Named Dean of Undergraduate Students

Starting on July 1, 2014, John Dabiri, professor of aeronautics and bioengineering, will serve as Caltech's dean of undergraduate students.

"John is particularly committed to enhancing faculty-student interactions. His experience as chair of the faculty and as faculty in residence in Avery House make me confident he will do a great job," says Anneila Sargent, vice president for student affairs and the Ira S. Bowen Professor of Astronomy.

The role of dean of undergraduate students is to foster academic and personal growth through counseling and support for student activities as well as act as a liaison between students and faculty.

"I've been fortunate to interact with Caltech undergrads as a visiting SURF student, a graduate student, and as a professor," says Dabiri. "Those experiences have proven to me that the creative and maverick spirit that is the Caltech brand really begins with our undergrads, and I look forward to helping nurture that spirit."

Dabiri says that his first order of business as dean is to engage students in a conversation about their experience on campus.

"I'm looking forward to visiting each of the houses this term to solicit their feedback on student life at Caltech," says Dabiri, who lives with his family in Avery House as faculty in residence.

He also wants to include former students in talks about how to improve undergraduate life at Caltech.

"Our alumni provide a longer-term perspective that will be a valuable complement to student input, and I hope they won't be shy in providing it," says Dabiri. "I also want to challenge our esteemed alumni and other friends to invest the time and resources needed to ensure that the student experience at Caltech is unparalleled in terms of the opportunities it affords for academic and personal development."

He cites greater exposure to entrepreneurship and the arts as examples of important complements to the existing Caltech education.

Dabiri, who is currently chair of the faculty, will take the reins from Rod Kiewiet, professor of political science, who began his term as dean of undergraduate students in July 2011.

"It's essential that we continue the important work Dean Kiewiet has initiated in developing a comprehensive social safety net within the house system," says Dabiri. "I'm also eager to receive the recommendations of the ongoing ad hoc committee on undergraduate self-governance, which should provide our students with greater opportunities to develop leadership skills through management of the houses."

Dabiri received his undergraduate degree in mechanical and aerospace engineering from Princeton University in 2001. He earned both his MS ('03) in aeronautics and PhD ('05) in bioengineering from Caltech, joining the faculty upon completion of his doctoral studies in 2005. A 2010 MacArthur Fellow, he is director of Caltech's Biological Propulsion Laboratory.  

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Spring Break in the Galápagos

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Spring Break in the Galápagos
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Credit: Kevin Yu

As the culminating event of the new Evolution course at Caltech, a dozen Techers, their TA, and two professors—Rob Phillips and Victoria Orphan—spent a week of spring break living as field researchers on the Galápagos Islands.

Credit: Kevin Yu

Ecuadorian naturalist Ernesto Vaca led the group in their studies of the natural world on the Galápagos. Here, at Playa Las Bachas on Santa Cruz Island, he is describing the molting of the Sally Lightfoot crab. The students kept scientific journals during the trip, writing down questions and observations along the way.

Credit: Laura Santoso

Marine iguanas are endemic to the Galápagos and are the only modern lizards that swim. They offer an excellent example of the way isolation on islands can lead to unique speciation.

Credit: Jeff Marlow

The group's home base for the trip was the research vessel Daphne, shown here anchored in James Bay.

Credit: Jeff Marlow

The group walks over solidified volcanic ash on Santiago Island.

Credit: Victoria Orphan

Flightlessness is one of the key evolutionary adaptations seen on islands. Here, a flightless cormorant is seen diving to gather food.

Credit: Kevin Yu

The landscape of Cerro Dragón (Dragon Hill) on Santa Cruz Island. This was one of many sites where the students were able to see the impact of invasive species such as goats.

Credit: Laura Santoso

The group's mascot—a Darwin bobblehead doll—posing in front of the third largest oceanic caldera in the world at the Sierra Negra volcano.

Credit: Pushpa Neppala

The Sierra Negra volcano on Santa Cruz Island.

Credit: Jeff Marlow

A young sea lion serves as an unexpected roadblock upon the group's arrival at North Seymour Island.

Credit: Ketaki Panse

A blue-footed booby perched atop a volcanic rock on North Seymour Island.

Credit: Laura Santoso

A land iguana with the island Daphne Minor in the background. One of the central questions about the iguanas on the Galápagos is how they arrived on the islands in the first place.

Credit: Aleena Patel

Part of the group explores a mangrove lagoon in Elizabeth Bay on Isla Isabela. According to Orphan, the mangroves are a nursery for many animals, and she encouraged the students to examine the mangrove roots closely. "Really looking closely, you start to see little transparent shrimp running up and down. There's a lot of richness that you can see even by just sitting and observing," she says.

Credit: Ketaki Panse

A beautiful sunset seen from the top of Bartholomew Island.

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As the final element of Evolution, Caltech's new Bi/Ge 105 course, a dozen students spent their spring break snorkeling with penguins and sharks, hiking a volcano, and otherwise taking in the natural laboratory for evolution that is the Galápagos Islands. The second-term course was created and is taught by Rob Phillips, the Fred and Nancy Morris Professor of Biophysics and Biology, and Victoria Orphan, professor of geobiology, and is designed to give students both a broad picture of evolution and a chance to make their own up-close-and-personal observations.

 

Caltech Researchers Discover the Seat of Sex and Violence in the Brain

As reported in a paper published online today in the journal Nature, Caltech biologist David J. Anderson and his colleagues have genetically identified neurons that control aggressive behavior in the mouse hypothalamus, a structure that lies deep in the brain (orange circle in the image at right). Researchers have long known that innate social behaviors like mating and aggression are closely related, but the specific neurons in the brain that control these behaviors had not been identified until now.

The interdisciplinary team of graduate students and postdocs, led by Caltech senior research fellow Hyosang Lee, found that if these neurons are strongly activated by pulses of light, using a method called optogenetics, a male mouse will attack another male or even a female. However, weaker activation of the same neurons will trigger sniffing and mounting: mating behaviors. In fact, the researchers could switch the behavior of a single animal from mounting to attack by gradually increasing the strength of neuronal stimulation during a social encounter (inhibiting the neurons, in contrast, stops these behaviors dead in their tracks).

These results suggest that the level of activity within the population of neurons may control the decision between mating and fighting.  

The neurons initially were identified because they express a protein receptor for the hormone estrogen, reinforcing the view that estrogen plays an important role in the control of male aggression, contrary to popular opinion. Because the human brain contains a hypothalamus that is structurally similar to that in the mouse, these results may be relevant to human behavior as well.

The results of the study were published in journal Nature on April 16. David J. Anderson is the Seymour Benzer Professor of Biology and an investigator with the Howard Hughes Medical Institute.

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For Cells, Internal Stress Leads to Unique Shapes

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these cells individually take on their own unique forms, Caltech biologist Elliot Meyerowitz, postdoctoral scholar Arun Sampathkumar, and colleagues sought to pinpoint the shape-controlling factors in pavement cells, which are puzzle-piece-shaped epithelial cells found on the leaves of flowering plants. They found that these unusual shapes were the cell's response to mechanical stress on the microtubule cytoskeleton—protein tubes that act as a scaffolding inside the cells. These microtubules guide oriented deposition of cell-wall components, thus providing structural support.

The researchers studied this supportive microtubule arrangement in the tissue of pavement cells from the first leaves—or cotyledons—of a young Arabidopsis thaliana plant (right). By fluorescently marking the cells' microtubules (yellow, top surface of cell; purple, bottom surface of cell), the researchers could image the cell's structural arrangement—and watch how this arrangement changed over time. They could also watch the microtubule modifications that occurred due to changes in the mechanical forces experienced by the cells.

Microtubules strengthen a cell's structure by lining up in the direction of stress or pressure experienced by the cell and guiding the deposition of new cell-wall material, providing a supportive scaffold for the cell's shape. However, Meyerowitz and colleagues found that this internal stress is also influenced by the cell's shape. The result is a feedback loop: the cell's shape influences the microtubule arrangement; this arrangement, in turn, affects the cell's shape, which modulates the microtubules, and so on. Therefore, the unusual shape of the pavement cell represents a state of balance—an individual cell's tug-of-war to maintain structural integrity while also dynamically responding to the pushes and pulls of mechanical stress.

The results of the study were published in the journal eLife on April 16. Elliot Meyerowitz is George W. Beadle Professor of Biology and an investigator with the Howard Hughes Medical Institute.

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Antennae Help Flies "Cruise" In Gusty Winds

Caltech researchers uncover a mechanism for how fruit flies regulate their flight speed, using both vision and wind-sensing information from their antennae.

Due to its well-studied genome and small size, the humble fruit fly has been used as a model to study hundreds of human health issues ranging from Alzheimer's to obesity. However, Michael Dickinson, Esther M. and Abe M. Zarem Professor of Bioengineering at Caltech, is more interested in the flies themselves—and how such tiny insects are capable of something we humans can only dream of: autonomous flight. In a report on a recent study that combined bursts of air, digital video cameras, and a variety of software and sensors, Dickinson and his team explain a mechanism for the insect's "cruise control" in flight—revealing a relationship between a fly's vision and its wind-sensing antennae.

The results were recently published in an early online edition of the Proceedings of the National Academy of Sciences.

Inspired by a previous experiment from the 1980s, Dickinson's former graduate student Sawyer Fuller (PhD '11) wanted to learn more about how fruit flies maintain their speed in flight. "In the old study, the researchers simulated natural wind for flies in a wind tunnel and found that flies maintain the same groundspeed—even in a steady wind," Fuller says.

Because the previous experiment had only examined the flies' cruise control in gentle steady winds, Fuller decided to test the limits of the insect's abilities by delivering powerful blasts of air from an air piston in a wind tunnel. The brief gusts—which reached about half a meter per second and moved through the tunnel at the speed of sound—were meant to probe how the fly copes if the wind is rapidly changing.

The flies' response to this dynamic stimulus was then tracked automatically by a set of five digital video cameras that recorded the fly's position from five different perspectives. A host of computers then combined information from the cameras and instantly determined the fly's trajectory and acceleration.

To their surprise, the Caltech team found that the flies in their experiments, unlike those in the previous studies, accelerated when the wind was pushing them from behind and decelerated when flying into a headwind. In both cases the flies eventually recovered to maintain their original groundspeed, but the initial response was puzzling, Fuller says. "This response was basically the opposite of what the fly would need to do to maintain a consistent groundspeed in the wind," he says.

In the past, researchers assumed that flies—like humans and most other animals—used their vision to measure their speed in wind, accelerating and decelerating their flight based on the groundspeed their vision detected. But Fuller and his colleagues were also curious about the in-flight role of the fly's wind-sensing organs: the antennae.

Using the fly's initial response to strong wind gusts as a marker, the researchers tested the response of each sensory mode individually. To investigate the role of wind sensation on the fly's cruise control, they delivered strong gusts of wind to normal flies, as well as flies whose antennae had been removed. The flies without antenna still increased their speed in the same direction as the wind gust, but they only accelerated about half as much as the flies whose antennae were still intact. In addition, the flies without antennae were unable to maintain a constant speed, dramatically alternating between acceleration and deceleration. Together, these results suggested that the antennae were indeed providing wind information that was important for speed regulation.

In order to test the response of the eyes separately from that of the antennae, Fuller and his colleagues projected an animation on the walls of the fly-tracking arena that would trick the eyes into thinking there was no speed increase, even though the antenna could feel the increased windspeed. When the researchers delivered strong headwinds to flies in this environment, the flies decelerated and were unable to recover to their original speed.

"We know that vision is important for flying insects, and we know that flies have one of the fastest visual systems on the planet," Dickinson says, "But this response showed us that as fast as their vision is, if they're flying too fast or the wind is blowing them around too quickly, their visual system reaches its limit and the world starts getting blurry." That is when the antennae kick in, he says.

The results suggest that the antennae are responsible for quickly sensing changes in windspeed—and therefore are responsible for the fly's initial deceleration in a headwind. The information received from the fly's eyes—which is processed much more slowly than information from the wind sensors on the antenna—is responsible for helping the fly regain its cruising speed.

"Sawyer's study showed that the fly can take another sensor—this little tiny antenna, which doesn't require nearly the amount of processing area within the brain as the eyes—and the fly is able to use that information to compensate for the fact that the information coming out of the eyes is a bit delayed," Dickinson says. "It's kind of a neat trick, using a cheap little sensor to compensate for the limitations of a big, heavy, expensive sensor."

Beyond learning more about the fly's wind-sensing capabilities, Fuller says that this information will also help engineers design small flying robots—creating a sort of man-made fly. "Tiny flying robots will take a lot of inspiration from flies. Like flies, they will probably have to rely heavily on vision to regulate groundspeed," he says.

"A challenge here is that vision typically takes a lot of computation to get right, just like in flies, but it's impossible to carry a powerful processor to do that quickly on a tiny robot. So they'll instead carry tiny cameras and do the visual processing on a tiny processor, but it will just take longer. Our results suggest that little flying vehicles would also do well to have fast wind sensors to compensate for this delay."

The work was published in a study titled "Flying Drosophila stabilize their vision-based velocity controller by sensing wind with their antennae." Other coauthors include former Caltech senior postdoc Andrew D. Straw, Martin Y. Peek (BS '06), and Richard Murray, Thomas E. and Doris Everhart Professor of Control and Dynamical Systems and Bioengineering at Caltech, who coadvised Fuller's graduate work. The study was supported by the Institute for Collaborative Biotechnologies through funding from the U.S. Army Research Office and by a National Science Foundation Graduate Fellowship.

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Spring Ombudsperson Training

Cell Biologist Alexander Varshavsky Wins Albany Medical Center Prize

Alexander Varshavsky, Howard and Gwen Laurie Smits Professor of Cell Biology at Caltech, has been named the recipient of the 2014 Albany Medical Center Prize in Medicine and Biomedical Research.

The award, of which Varshavsky is the sole recipient this year, recognizes him for his groundbreaking work in biology, specifically for the "discovery of critical molecular determinants and biological functions of intracellular protein degradation," a set of fundamentally important processes that is central to the physiology of both individual cells and multicellular organisms.

"Studies by my laboratory, initially at MIT and later at Caltech, focused on the understanding of how and why cells destroy their own proteins to withstand stress, to grow and divide, to differentiate into new kinds of cells, and to do countless other things that make living organisms so astonishing and fascinating," Varshavsky says.

He and colleagues in his lab have spent the past several decades studying the ubiquitin system, a set of biological pathways that have in common a small protein called ubiquitin. This highly complex system was found to mediate the regulated degradation of intracellular proteins, and other processes as well. It was gradually understood that functions of this system are relevant to just about everything that living cells do.

"The field of ubiquitin research has been expanding at an amazing pace, and is now one of the largest arenas in biomedical science," Varshavsky says. "Both earlier and recent discoveries illuminate the ubiquitin system and protein degradation from many different angles and continue to foster our ability to tackle human diseases, from cancer, infections, and cardiovascular illnesses to neurodegenerative syndromes and the aging process itself."

Varshavsky is the second Caltech faculty member to receive the $500,000 Albany Prize for research in life sciences. The late Caltech geneticist and molecular biologist Seymour Benzer was a recipient of the Albany Prize in 2006.

"I feel privileged having been able to contribute to the birth of my field, and to partake in its later development," Varshavsky says. "I am most grateful to distinguished members of the Albany Prize Committee for their decision to recognize our contributions with this major award."

Varshavsky received his BS from Russia's Moscow State University in 1970 and his PhD from Moscow's Institute of Molecular Biology in 1973. He has been Smits Professor at Caltech since 1992.

A member of the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, and the Academia Europaea, Varshavsky has received many international prizes in biology and medicine, including the 2014 Breakthrough Prize in Life Sciences, the 2012 King Faisal Prize for Science (Saudi Arabia), the 2011 Otto Warburg Prize (Germany), the 2008 Gotham Prize in Cancer Research, the 2006 Gagna and Van Heck Prize (Belgium), the 2006 Griffuel Prize (France), the 2005 Stein and Moore Award, the 2001 Horwitz Prize, the 2001 Merck Award, the 2001 Wolf Prize in Medicine (Israel), the 2000 Lasker Award in Basic Medical Research, and the 1999 Gairdner Award (Canada).

One of the largest awards for medicine and science in the United States, the Albany Prize was founded by businessman and philanthropist Morris "Marty" Silverman in 2000 to recognize scientists and physicians whose work has resulted in "significant outcomes that offer medical value of national or international importance." Varshavsky will be honored at a ceremony in Albany on May 21.

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