Alumnus Eric Betzig Wins 2014 Nobel Prize in Chemistry

Eric Betzig (BS '83), a group leader at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Virginia, has been awarded the 2014 Nobel Prize in Chemistry along with Stefan W. Hell of the Max Planck Institute for Biophysical Chemistry and William E. Moerner of Stanford University. The three were honored "for the development of super-resolved fluorescence microscopy," a method that allows for the creation of "super-images" with a resolution on the order of nanometers, or billionths of a meter. In essence, the work turns microscopy into "nanoscopy."

The technique developed by the trio overcomes the so-called Abbe diffraction limit, which describes a physical restriction on the sizes of the structures that can be resolved using optical microscopy, showing that, essentially, nothing smaller than one-half the wavelength of light, or about 0.2 microns, can be discerned by these scopes. The result of the Abbe limit is that only the larger structures within cells—organelles like mitochondria, for example—can be resolved and studied with regular microscopes but not individual proteins or even viruses. The restriction is akin to being able to observe the buildings that make up a city but not the city's inhabitants and their activities.

Betzig, building on earlier work by Hell and Moerner, found that it was possible to work around the Abbe limit to create very-high-resolution images of a sample, such as a developing embryo, by using fluorescent proteins that glow when illuminated with a weak pulse of light. Each time the sample is illuminated, a different, sparsely distributed subpopulation of fluorescent proteins will light up and, because the glowing molecules are spaced farther apart than the Abbe diffraction limit, a standard microscope would be able to capture them. Still, each of the images produced in this way has relatively low resolution—that is, they are blurry. Betzig, however realized that by superimposing many such images, he would be able to obtain a sharp super-image, in which nanoscale structures are clearly visible. The new technique was first described in a 2006 paper published in the journal Science.

After Caltech, Betzig, a physics major from Ruddock House, earned an MS (1985) and a PhD (1988) from Cornell University. He worked at AT&T Bell Laboratories until 1994, when he stepped away from academia and science to work for his father's machine tool company. Betzig returned to research in 2002 and joined Janelia in 2005.

To date, 33 Caltech alumni and faculty have won a total of 34 Nobel Prizes. Last year, alumnus Martin Karplus (PhD '54) also received the Chemistry Prize. 

Kathy Svitil
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Caltech Physics Professors Earn NASA Medals

James J. (Jamie) Bock, professor of physics at Caltech and a senior research scientist at JPL, and Caltech Professor of Physics Christopher Martin were among those receiving NASA Honor Awards from JPL director Charles Elachi (MS '69, PhD '71) and John Grunsfeld, NASA's associate administrator for the Science Mission Directorate, in a ceremony on Tuesday, September 16.

Bock was awarded NASA's Distinguished Service Medal for "accomplishments in cosmology including development and application of new detector technology leading to advances in our knowledge of the Universe."

Martin, the principal investigator for the Galaxy Evolution Explorer, an Earth-orbiting space telescope that studies the universe in ultraviolet light, was given the NASA Exceptional Scientific Achievement Medal, awarded for efforts resulting in key scientific discoveries or contributions of fundamental importance to the field in question, including, according to the award citation, "the new understanding of galaxy evolution, the identification of new environments for star formation, and an invaluable data archive of UV images of most of the sky."

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NuSTAR Discovers Impossibly Bright Dead Star

X-ray source in the Cigar Galaxy is the first ultraluminous pulsar ever detected

Astronomers working with NASA's Nuclear Spectroscopic Telescope Array (NuSTAR), led by Caltech's Fiona Harrison, have found a pulsating dead star beaming with the energy of about 10 million suns. The object, previously thought to be a black hole because it is so powerful, is in fact a pulsar—the incredibly dense rotating remains of a star.

"This compact little stellar remnant is a real powerhouse. We've never seen anything quite like it," says Harrison, NuSTAR's principal investigator and the Benjamin M. Rosen Professor of Physics at Caltech. "We all thought an object with that much energy had to be a black hole."

Dom Walton, a postdoctoral scholar at Caltech who works with NuSTAR data, says that with its extreme energy, this pulsar takes the top prize in the weirdness category. Pulsars are typically between one and two times the mass of the sun. This new pulsar presumably falls in that same range but shines about 100 times brighter than theory suggests something of its mass should be able to.

"We've never seen a pulsar even close to being this bright," Walton says. "Honestly, we don't know how this happens, and theorists will be chewing on it for a long time." Besides being weird, the finding will help scientists better understand a class of very bright X-ray sources, called ultraluminous X-ray sources (ULXs).

Harrison, Walton, and their colleagues describe NuSTAR's detection of this first ultraluminous pulsar in a paper that appears in the current issue of Nature.

"This was certainly an unexpected discovery," says Harrison. "In fact, we were looking for something else entirely when we found this."

Earlier this year, astronomers in London detected a spectacular, once-in-a-century supernova (dubbed SN2014J) in a relatively nearby galaxy known as Messier 82 (M82), or the Cigar Galaxy, 12 million light-years away. Because of the rarity of that event, telescopes around the world and in space adjusted their gaze to study the aftermath of the explosion in detail.

This animation shows a neutron star—the core of a star that exploded in a massive supernova. This particular neutron star is known as a pulsar because it sends out rotating beams of X-rays that sweep past Earth like lighthouse beacons. (Credit: NASA/JPL-Caltech)

Besides the supernova, M82 harbors a number of other ULXs. When Matteo Bachetti of the Université de Toulouse in France, the lead author of this new paper, took a closer look at these ULXs in NuSTAR's data, he discovered that something in the galaxy was pulsing, or flashing light.

"That was a big surprise," Harrison says. "For decades everybody has thought these ultraluminous X-ray sources had to be black holes. But black holes don't have a way to create this pulsing."

But pulsars do. They are like giant magnets that emit radiation from their magnetic poles. As they rotate, an outside observer with an X-ray telescope, situated at the right angle, would see flashes of powerful light as the beam swept periodically across the observer's field of view, like a lighthouse beacon.

The reason most astronomers had assumed black holes were powering ULXs is that these X-ray sources are so incredibly bright. Black holes can be anywhere from 10 to billions of times the mass of the sun, making their gravitational tug much stronger than that of a pulsar. As matter falls onto the black hole the gravitational energy turns it to heat, which creates X-ray light. The bigger the black hole, the more energy there is to make the object shine.

Surprised to see the flashes coming from M82, the NuSTAR team checked and rechecked the data. The flashes were really there, with a pulse showing up every 1.37 seconds.

The next step was to figure out which X-ray source was producing the flashes. Walton and several other Caltech researchers analyzed the data from NuSTAR and a second NASA X-ray telescope, Chandra, to rule out about 25 different X-ray sources, finally settling on a ULX known as M82X-2 as the source of the flashes.

With the pulsar and its location within M82 identified, there are still many questions left to answer. It is many times higher than the Eddington limit, a basic physics guideline that sets an upper limit on the brightness that an object of a given mass should be able to achieve.

"This is the most extreme violation of that limit that we've ever seen," says Walton. "We have known that things can go above that by a small amount, but this blows that limit away."

NuSTAR is particularly well-suited to make discoveries like this one. Not only does the space telescope see high-energy X-rays, but it sees them in a unique way. Rather than snapping images the way that your cell-phone camera does—by integrating the light such that images blur if you move—NuSTAR detects individual particles of X-ray light and marks when they are measured. That allows the team to do timing analyses and, in this case, to see that the light from the ULX was coming in pulses.

Now that the NuSTAR team has shown that this ULX is a pulsar, Harrison points out that many other known ULXs may in fact be pulsars as well. "Everybody had assumed all of these sources were black holes," she says. "Now I think people have to go back to the drawing board and decide whether that's really true. This could just be a very unique, strange object, or it could be that they're not that uncommon. We just don't know. We need more observations to see if other ULXs are pulsing."

Along with Harrison and Walton, additional Caltech authors on the paper, "An Ultraluminous X-ray Source Powered by An Accreting Neutron Star," are postdoctoral scholars Felix Fürst, and Shriharsh Tendulkar; research scientists Brian W. Grefenstette and Vikram Rana; and Shri Kulkarni, the John D. and Catherine T. MacArthur Professor of Astronomy and Planetary Science and director of the Caltech Optical Observatories. The work was supported by NASA and made use of data supplied by the UK Swift Science Data Centre at the University of Leicester.

Kimm Fesenmaier
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TMT Breaks Ground

Today at 3 p.m. PDT, a groundbreaking and blessing ceremony approximately 14,000 feet above sea level, near the summit of Hawaii's Mauna Kea, will officially kick off construction for the next-generation Thirty Meter Telescope (TMT).

The ceremony, preceded by pre-recorded science segments, can be viewed live beginning at 2:15 p.m. PDT. Log on to to watch the groundbreaking ceremonies. Viewers worldwide are welcome to send greetings to TMT (@TMTHawaii) via the hashtag #buildingTMT.

Henry Yang, chair of the TMT International Observatory (TIO) board and chancellor of the University of California, Santa Barbara, will deliver the groundbreaking program's opening remarks, followed by Hawaii Governor Neil Abercrombie and Hawaii County Mayor William Kenoi. The program will conclude with a traditional Hawaiian ceremony that will include Caltech President Thomas F. Rosenbaum. Also in attendance will be Provost Edward Stolper; Board of Trustees Chair David Lee (PhD, '74); Senior Trustee Walter L. Weisman and Life Trustee Gordon Moore (PhD, '54); Tom Soifer (BS, '68), Kent and Joyce Kresa Leadership Chair of the Division of Physics, Mathematics and Astronomy; Ed Stone, the David Morrisroe Professor of Physics and TIO executive director; and other members of the Caltech administration and faculty.

When completed, TMT will be the world's most advanced optical/near-infrared observatory, offering the highest-definition views ever achieved of planets orbiting nearby stars and the first stars and galaxies in the distant universe, and enabling researchers to tackle some of humanity's most fundamental and elusive questions.

Caltech, in collaboration with the University of California and scientists from Japan, China, India, and Canada, and with generous financial support from the Gordon and Betty Moore Foundation, spearheaded the design and construction of the $1.4 billion project, which was first conceived more than a decade ago.

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TMT Groundbreaking Launches New Era of Discovery

Construction officially has begun near the summit of Hawaii's Mauna Kea on what will be the largest telescope on the planet: the Thirty Meter Telescope (TMT).

"It is both exhilarating and intimidating to have reached this point," says Tom Soifer, professor of physics and Kent and Joyce Kresa Leadership Chair of the Division of Physics, Mathematics and Astronomy at Caltech. "It is exhilarating because of the enormous amount of effort it has taken us to get here and because, now that we are at the groundbreaking, TMT—and the scientific opportunities it brings—becomes much more real. It is intimidating because we've only just begun the work."

TMT, which is scheduled to begin observations in the early 2020s, will join the family of observatories already on Mauna Kea, including Caltech's twin 10-meter telescopes at the W. M. Keck Observatory, the current record-holder for the largest optical and infrared telescope in the world.

At 10 to 100 times more sensitive than Keck—depending on the type of observation—TMT is designed to tackle the most challenging questions of the cosmos, such as whether there is life on planets beyond the solar system, the nature of dark energy and dark matter, and the formation and evolution of galaxies.

Wide-angle view of 200-inch Hale Telescope
Credit: Scott Kardel

Caltech has played a leading role in the conception, design, and construction of the TMT, the latest (and greatest) of the Institute's pioneering efforts to build the most powerful observatories in the world. In the early 20th century, astronomer George Ellery Hale, one of the founders of Caltech, spearheaded the construction of the 200-inch telescope at Palomar Observatory, which stood as the largest telescope for 45 years until 1993 when Caltech and the University of California built the W. M. Keck Observatory. The Hale Telescope, as it became known, helped astronomers measure the expansion of the universe and discover exotic, bright objects called quasars, among numerous other achievements.

The twin 10-meter Keck telescope domes on Mauna Kea, Hawaii
Credit: Rick Peterson/WMKO

Caltech was also instrumental in the design and construction of Keck, which has become the preeminent optical and infrared observatory in the world. Over the last two decades, astronomers from around the globe—including many at Caltech—have used the twin Keck telescopes to detect planets beyond the solar system and peer into other planetary systems; probe the black hole at the center of the Milky Way galaxy; learn how the universe has evolved since the Big Bang, how galaxies form, and how stars are born; and to study dark matter, the mysterious stuff that makes up most of the universe's mass, and dark energy, the enigmatic force that's expanding the universe at an ever-faster rate.

The design of TMT and its instruments are based on Keck—only bigger, faster, and better. For example, each Keck telescope comprises 36 hexagonal mirror segments, which together act as a 10-meter-wide mirror. TMT, on the other hand, will have 492 segments that function as a 30-meter-wide mirror.

With such light-gathering ability, state-of-the-art instruments, and a first-ever fully integrated adaptive optics system to cancel out the blurring effects of the atmosphere, TMT will be able to see farther and more clearly than Keck or any other telescope at the same optical and infrared wavelengths.

For example, it will capture unprecedented images of planets beyond our solar system, revealing their atmospheres and environments in detail, and bring astronomers closer to answering the question of whether there is life elsewhere in the universe.

TMT will study how galaxies form and evolve, and how they're distributed across the universe. By exploring the large-scale structure of the universe and how it has changed over time, astronomers can probe dark energy and dark matter, as-yet invisible stuff that seems to interact only gravitationally with ordinary matter like stars. Both comprise the vast majority of the matter and energy in the universe and remain one of the most confounding questions in science.

The telescope will peer back in time to observe the first galaxies that came into existence 13 billion years ago, unveiling an era of cosmic history just beyond the reach of current telescopes.

TMT will study black holes that are millions to billions of times as massive as the sun and reside at the center of distant galaxies. It will also examine enormous explosions known as gamma-ray bursts, which are the most powerful events in the universe.

But what has many astronomers the most excited is not the expected discoveries, but the surprises that await, says Ed Stone, Caltech's David Morrisroe Professor of Physics and executive director of the TMT International Observatory, an international partnership that includes Caltech, the National Astronomical Observatories of the Chinese Academy of Sciences, the National Institutes of Natural Sciences in Japan, and the University of California. "It's not just about understanding better what you already know but learning what you didn't even know was out there," he says.

These future discoveries, Soifer adds, would not be possible were it not for the vision and continuing support of Caltech's collaborators and partners. "Gordon and Betty Moore and the Moore Foundation have been essential to getting TMT where we are today," Soifer says. That support began with a gift of $140 million to Caltech and the University of California to develop the early concept of a telescope larger than Keck. "The foundation has continued to provide the critical support that has allowed the project to continue," he says. "TMT is a testament to the Moore Foundation, our ingenuity, and the spirit of exploration."

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Tuesday, October 7, 2014
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Caltech Researchers Receive NIH BRAIN Funding

On September 30, the National Institutes of Health (NIH) announced its first round of funding in furtherance of President Obama's "Brain Research through Advancing Innovative Neurotechnology"—or BRAIN—Initiative. Included among the 58 funded projects—all of which, according to the NIH, are geared toward the development of "new tools and technologies to understand neural circuit function and capture a dynamic view of the brain in action"—are six projects either led or co-led by Caltech researchers.

The Caltech projects are:

"Dissecting human brain circuits in vivo using ultrasonic neuromodulation"

Doris Tsao, assistant professor of biology
Mikhail Shapiro, assistant professor of chemical engineering

Tsao and Shapiro are teaming up to develop a new technology that both uses ultrasound to map and determine the function of interconnected brain networks and, ultimately, to change neural activity deep within the brain. "This would open new horizons for understanding human brain function and connectivity, and create completely new options for the noninvasive treatment of brain diseases such as intractable epilepsy, depression, and Parkinson's disease," Tsao says. "The key," Shapiro adds, "is to gain a precise understanding of the various mechanisms by which sound waves interact with neurons in the brain so we can use ultrasound to produce very specific neurological effects. We will be able to do this across the full spectrum, from molecules up to large model organisms."

"Modular nanophotonic probes for dense neural recording at single-cell resolution"

Michael Roukes, Robert M. Abbey Professor of Physics, Applied Physics, and Bioengineering
Thanos Siapas, professor of computation and neural systems

Roukes, Siapas, and their colleagues at Columbia University and Baylor College of Medicine propose to build ultra-dense arrays of miniature light-emitting and light-sensing probes using advanced silicon "chip" technology that permits their production en masse. These probes open the new field of integrated neurophotonics, Roukes says, and will permit simultaneous recording of the electrical activity of hundreds of thousands to, ultimately, millions of neurons, with single-cell resolution, in any given region of the brain. "The instrumentation we'll develop will enable us to observe the trafficking of information, in vivo, in brain circuits on an unprecedented scale, and to correlate this activity with behavior," he says.

"Time-Reversal Optical Focusing for Noninvasive Optogenetics"

Changhuei Yang, professor of electrical engineering, bioengineering, and medical engineering
Viviana Gradinaru, assistant professor of biology

Deep-brain stimulation has been used successfully for nearly two decades for the treatment of epilepsy, Parkinson's disease, chronic pain, depression, and other disorders. Current systems rely on electrodes implanted deep within the brain to modify the firing pattern of specific clusters of neurons, bringing them back into a more normal pattern. Yang and Gradinaru are working together on a method that would use only light waves to noninvasively activate light-sensitive molecules and precisely guide the firing of nerves. Biological tissues are opaque due to the scattering of light waves, and that scattering makes it impossible to finely focus a laser beam deep into brain tissue. The researchers hope to use an optical "time-reversal" trick previously developed by Yang to counteract the scattering, allowing light beams to be targeted to specific locations within the brain. "The technology to be developed in this project has the potential for wide-ranging applications, including noninvasive deep brain stimulation and precise incisionless laser surgery," he says.

"Integrative Functional Mapping of Sensory-Motor Pathways"

Michael H. Dickinson, Esther M. and Abe M. Zarem Professor of Bioengineering

As in other animals, locomotion in the fruit fly is a complicated process involving the interplay of sensory systems and motor circuits in the brain. Dickinson and his colleagues hope to decipher just how the brain uses sensory information to guide movements by developing a system to record the activity of large numbers of individual neurons from across the brains of fruit flies, as the flies fly in flight simulator or walk on a treadmill and are simultaneously exposed to various sights and sounds. Understanding sensory–motor integration, he says, should lead to a better understanding of human disorders, including Parkinson's disease, stroke, and spinal cord injury, and aid in the design and optimization of robotic prosthetic limbs and prosthetic devices that restore sight and other senses.

"Establishing a Comprehensive and Standardized Cell Type Characterization Platform"

David J. Anderson, Seymour Benzer Professor of Biology; Investigator, Howard Hughes Medical Institute (co-PI)

In collaboration with Hongkui Zeng and colleagues at the Allen Institute for Brain Science in Seattle, Anderson will help to develop a detailed, publicly available database characterizing the genetic, physiological, and morphological features of the various cell types in the brain that are involved in circuits controlling sensations and emotions. Understanding the cellular building blocks of brain circuits, the researchers say, is crucial for figuring out how those circuits can malfunction in disease. In particular, Anderson's lab will focus on the cells of the brain's hypothalamus and amygdala—structures that are vital to emotions and behavior, and involved in human psychiatric disorders such as post-traumatic stress disorder, anxiety, and depression. "This project will serve as a model for hub-and-spoke collaborations between academic laboratories and the Allen Institute, permitting access to their valuable resources and technologies while advancing the field more broadly," Anderson says.

"Vertically integrated approach to visual neuroscience: microcircuits to behavior"

Markus Meister, Lawrence A. Hanson, Jr. Professor of Biology (co-PI)

This project, led by Hyunjune Sebastian Seung of Princeton University, will use genetic, electrophysiological, and imaging tools to identify and map the neural connections of the retina, the light-sensing tissue in the eye, and determine their roles in visual perception and behavior. "Here we are shooting for a vertically integrated understanding of a neural system," Meister says. "The retina offers such a fantastic degree of experimental access that one can hope to bridge all scales of organization, from molecules to cells to microcircuits to behavior. We hope that success here can eventually serve as a blueprint for understanding other parts of the brain." Knowing the neural mechanisms for vision can also influence technological applications, such as new algorithms for computer vision, or the development of retinal prostheses for the treatment of blindness.

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Tuesday, October 7, 2014
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Thirty Meter Telescope Groundbreaking and Blessing

Sunday, October 5, 2014
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Sunday, October 5, 2014
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