Caltech Awards International Aerospace Honor to Satellite Pioneer

Sir Martin Sweeting, founder and executive chairman of Surrey Satellite Technology Limited (SSTL) and director of the Surrey Space Centre at the University of Surrey, is the 2012 recipient of the International von Kármán Wings Award. The award—presented annually by the Aerospace Historical Society, which is part of the Graduate Aerospace Laboratories at Caltech (GALCIT)—acknowledges outstanding contributions by international innovators, leaders, and pioneers in aerospace.

Sweeting has been recognized for his technical and leadership contributions to aerospace academia and industry—in particular, for pioneering the concept of rapid-response, low-cost, and highly capable small satellites for Earth observation, communications, and space science.

"Professor Sweeting's pioneering work on small satellites, in addition to its inherent engineering and scientific value, is also helping to educate the next generation of aerospace engineers," says Ares Rosakis, chair of Caltech's Division of Engineering and Applied Science, Theodore von Kármán Professor of Aeronautics, and professor of mechanical engineering. "It is an honor to give this award, named after the founder of the Jet Propulsion Laboratory—and the founding director of GALCIT—to Professor Sweeting."

A leading authority on satellite technology, Sweeting is a Distinguished Professor at the University of Surrey and a Fellow of the Royal Society. He founded SSTL in 1981, with a vision of making space more accessible. Utilizing modern commercial off-the-shelf technology, SSTL has developed a new market for small but advanced satellites and provides innovative and reliable cost-effective solutions for established space agencies, emerging-nation space programs, and commercial and research organizations.

"It is a privilege to be recognised in the von Kármán Wings Award, and to share this accolade with visionaries and innovators that I greatly admire," said Sweeting in an SSTL press release. "During my career, small satellites have developed from being a research curiosity to become instrumental in scientific research, understanding our planet, and satellite navigation—I am thrilled to have played a part to make this all possible."

Guruswami Ravichandran, chair of the Aerospace Historical Society, director of GALCIT, and the John E. Goode, Jr., Professor of Aeronautics and Mechanical Engineering at Caltech, presented the Wings Award to Sweeney at a gala banquet and awards ceremony on September 13 at the Caltech Athenaeum.

Previous recipients of the Wings Award include Joanne Maguire, aerospace engineer and executive vice president of Lockheed Martin Space Systems Company; Abdul Kalam, the 11th president of India; Yannick d'Escatha, the chairman and CEO of the French space agency, Centre National d'Études Spatiales; Caltech alumnus Alexis Livanos (BS '70, MS '73, PhD '75), former corporate vice president and chief technology officer for Northrop Grumman; Charles Elachi (MS '69, PhD '71), director of the Jet Propulsion Laboratory (JPL); Kent Kresa, former chairman and CEO of Northrop Grumman and chairman of Caltech's Board of Trustees; Burt Rutan, aerospace entrepreneur and founder of Scaled Composites; aerospace pioneer Paul MacCready (MS '48, PhD '52); Edward Stone, the David Morrisroe Professor of Physics at Caltech and former director of JPL; and astronaut Buzz Aldrin.

For more information on the International von Kármán Wings Award, the Aerospace Historical Society, and 2012 recipient Sir Martin Sweeting, go to http://www.galcit.caltech.edu/ahs.

For more about GALCIT, go to http://www.galcit.caltech.edu/.

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Notes from the Back Row: "Taming Turbulence"

"Turbulence is everywhere," says Beverley McKeon—from continent-spanning weather systems down to the swirls of air your car leaves behind itself as you drive. "I think about things like ships, planes, and pipelines," she explains, noting that about half of the energy consumed by each of those three transportation systems goes to counteract turbulence-induced drag. In her Watson Lecture on May 16, 2012, McKeon, a professor of aeronautics at Caltech, notes that finding a way to reduce that turbulence by 30 percent would save the global economy well over $100,000,000 dollars in fuel costs annually.

Unfortunately, says McKeon, turbulent drag or "skin friction" is inevitable. Even the smoothest airplane wing is rough on the atomic level. A thin layer of air molecules sticks to this uneven surface, and they pull their neighbors along with them rather than allowing them to slide smoothly by. Those molecules, in turn, pull their neighbors along after them, although not as hard, and so on and so on until eventually the air flows around the wing undisturbed. Or, looking at it from the aircraft's point of view, the plane has to shoulder its way through a sticky, resistant fluid.

This "boundary layer" between the wing and the free-flowing air is only up to a few handbreadths thick. The turbulent structures within it are chaotic, says McKeon, yet they have their own weird orderliness—a hint that they may be open to manipulation. But controlling them "is like herding cats," she says, noting that her goal is to learn how "to tickle the flow—to make it do what it thinks it wants to do, but is really what I want it to do." 

"Taming Turbulence" is available for download in HD from Caltech on iTunesU. (Episode 12)

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Caltech Wins Toilet Challenge

Caltech's solar-powered toilet has won the Reinventing the Toilet Challenge issued by the Bill and Melinda Gates Foundation. Caltech engineer Michael Hoffmann and his colleagues were awarded $100,000 for their design, which they demonstrated at the Reinvent the Toilet Fair, a two-day event held August 14–15 in Seattle.

Last summer, Hoffmann, the James Irvine Professor of Environmental Science at Caltech, and his team were awarded a $400,000 grant to create a toilet that can safely dispose of human waste for just five cents per user per day. The lavatory can't use a septic system or an outside water source, or produce pollutants.

The challenge is part of a $40 million program initiated by the Gates Foundation to tackle the problems of water, sanitation, and hygiene throughout the developing world. According to the World Health Organization, 2.5 billion people around the globe are without access to sanitary toilets, which results in the spread of deadly diseases. Every year, 1.5 million people—mostly those under the age of five—die from diarrhea.

Hoffmann's proposal—which won one of the eight grants given—was to build a toilet that uses the sun to power an electrochemical reactor. The reactor breaks down water and human waste into fertilizer and hydrogen, which can be stored in hydrogen fuel cells as energy. The treated water can then be reused to flush the toilet or for irrigation.

The team built a prototype inside the solar dome on the roof of Caltech's Linde + Robinson Laboratory, and after a year of designing and testing, they—along with the other grantees—showed off their creation. The Gates Foundation brought in 50 gallons of fake feces made from soybeans and rice for the demonstrations.

The $60,000 second-place prize went to Loughborough University in the United Kingdom—whose toilet produces biological charcoal, minerals, and clean water—and the $40,000 third-place award went to the University of Toronto's design, which sanitizes feces and urine and recovers resources and clean water. Eawag (Swiss Federal Institute of Aquatic Science and Technology) and EOOS won $40,000 as a special recognition for their toilet interface design.

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White House Honors Caltech and JPL Scientists and Engineers

White House Honors Caltech and JPL Scientists and Engineers with the Presidential Early Career Award

PASADENA, Calif.—Chiara Daraio, professor of aeronautics and applied physics, and Christopher Hirata, professor of astrophysics, both at the California Institute of Technology (Caltech), and Ian Clark of NASA's Jet Propulsion Laboratory (JPL)—which is managed by Caltech—are winners of the Presidential Early Career Award for Scientists and Engineers. This is the highest award given by the United States government to science and engineering professionals in the early stages of their independent research careers.

Daraio was recognized by the Department of Defense for her "pioneering contributions to nonlinear mechanical phenomena in acoustic crystals, granular material, and multifunctional nanostructures, and for mentoring women and providing research opportunities for high school and undergraduate students."

Daraio arrived at Caltech in 2006. She leads a research group that focuses on the design, realization, and testing of materials with novel mechanical properties. Materials developed by Daraio's research group can be used in impact-mitigation systems, in protecting mechanical systems from undesired vibrations, and in new biomedical devices for imaging and diagnostics.

"I am very excited about this award. I wanted to be an inventor and engineer early on. I came to the U.S. as a graduate student and am grateful that here I could pursue my dreams," says Daraio. "Caltech has provided me with an excellent environment to realize my ideas, working with the world's best students, postdocs, and colleagues on the faculty."

"The entire Caltech community is proud to see Professor Daraio recognized with this presidential honor, not only for her pioneering research accomplishments, but also for her commitment to students and diversity," says Ares J. Rosakis, chair of Caltech's Division of Engineering and Applied Science, Theodore von Kármán Professor of Aeronautics, and professor of mechanical engineering. "Even though she is near the beginning of her career she already embodies the key attributes of the Division of Engineering and Applied Science at Caltech."

Daraio added, "This has been a very special year for me: I had a baby just two months ago, and a few weeks earlier became a U.S. citizen. The Presidential Early Career Award is the icing on the cake."

Daraio was born in Italy and received a degree in mechanical engineering from the Marche Polytechnic University in Ancona. She received both an MS and PhD in materials science and engineering from the University of California, San Diego.

Hirata was recognized by the Department of Energy for "innovative work reducing astrophysical uncertainties that limit the extraction of fundamental physics parameters from cosmological observations, for studies of the sensitivity of structure formation to the relative velocity between dark matter and baryons in the early universe, and for service on NASA/DOE Joint Dark Energy Mission working groups."

Hirata received his BS from Caltech in 2001, a time in which significant discoveries were being made in cosmology and high-energy physics. These discoveries guided him toward further studies into topics such as what happened in the first fraction of a second in the life of the universe, how galaxies are formed, and the fundamental nature and geometry of the universe. He earned his PhD at Princeton University and returned to Caltech as a faculty member in 2007.

"In the past decade, cosmology has been revolutionized by ever-improving observational capabilities. My colleagues and I have been developing the theoretical tools that enable us to connect the direct observables—the cosmic microwave background and the distribution of galaxies—to the underlying physical processes that occurred during the first fraction of a second after the big bang," says Hirata.

"I'm extremely pleased to see the national recognition of Chris Hirata's promise and achievement," says B. Thomas Soifer, chair of Caltech's Division of Physics, Mathematics and Astronomy, director of the Spitzer Science Center, and professor of physics. "His work is vital to our understanding of the formation and evolution of structures, such as galaxies, in the universe, and the award recognizes his leadership in this area."

"When I received word about winning this award, I was in the middle of debugging software code, so the work continues," Hirata says. "But it's nice to take a step back and see how far we have come. "

Clark was recognized by NASA for "exceptional leadership and achievement in the pursuit of advanced entry, descent and landing technologies and techniques for space-exploration missions."

"It's certainly quite an honor," says Clark. "However, there are remarkable achievements every day here at JPL/Caltech that are equally deserving of recognition. I wish we could honor the JPL and NASA teams for the amazing work on the Mars Science Laboratory as we prepare for it to land on Mars." 

"Discoveries in science and technology not only strengthen our economy, they inspire us as a people." President Obama said. "The impressive accomplishments of today's awardees so early in their careers promise even greater advances in the years ahead. "

The Presidential Early Career Award for Scientists and Engineers was established by President Clinton in 1996 and is coordinated by the President's Office of Science and Technology Policy. Awardees are selected for their pursuit of innovative research at the frontiers of science and technology, and their commitment to community service as demonstrated through scientific leadership, public education, or community outreach. Fourteen Caltech professors and researchers have won the award since its inception.

Caltech is recognized for its highly select student body of approximately 1,000 undergraduates and 1,300 graduate students, and for its outstanding faculty. Since 1923, Caltech faculty and alumni have garnered 32 Nobel Prizes and seven Crafoord Prizes. In addition to its prestigious on-campus research programs, Caltech operates the Jet Propulsion Laboratory (JPL); the W. M. Keck Observatory on Mauna Kea, in Hawaii; the Palomar Observatory; and the Laser Interferometer Gravitational-Wave Observatory (LIGO). Caltech is a private university in Pasadena, California. For more information, visit http://www.caltech.edu.

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Medusa Reimagined

Caltech-led team reverse engineers a jellyfish with the ability to swim

PASADENA, Calif.—When one observes a colorful jellyfish pulsating through the ocean, Greek mythology probably doesn't immediately come to mind. But the animal once was known as the medusa, after the snake-haired mythological creature its tentacles resemble. The mythological Medusa's gaze turned people into stone, and now, thanks to recent advances in bio-inspired engineering, a team led by researchers at the California Institute of Technology (Caltech) and Harvard University have flipped that fable on its head: turning a solid element—silicon—and muscle cells into a freely swimming "jellyfish."

Their method for building the tissue-engineered jellyfish, dubbed Medusoid, is outlined in a Nature Biotechnology paper that appears as an advance online publication on July 22. 

"A big goal of our study was to advance tissue engineering," says Janna Nawroth, a doctoral student in biology at Caltech and lead author of the study. "In many ways, it is still a very qualitative art, with people trying to copy a tissue or organ just based on what they think is important or what they see as the major components—without necessarily understanding if those components are relevant to the desired function or without analyzing first how different materials could be used." Because a particular function—swimming, say—doesn't necessarily emerge just from copying every single element of a swimming organism into a design, "our idea," she says, "was that we would make jellyfish functions—swimming and creating feeding currents—as our target and then build a structure based on that information."

Jellyfish are believed to be the oldest multi-organ animals in the world, possibly existing on Earth for the past 500 million years. Because they use a muscle to pump their way through the water, their function—on a very basic level—is similar to that of a human heart, which makes the animal a good biological system to analyze for use in tissue engineering.

"It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps," says Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at Harvard and a coauthor of the study. "I started looking at marine organisms that pump to survive. Then I saw a jellyfish at the New England Aquarium, and I immediately noted both similarities and differences between how the jellyfish pumps and the human heart. The similarities help reveal what you need to do to design a bio-inspired pump."

Parker contacted John Dabiri, professor of aeronautics and bioengineering at Caltech—and Nawroth's advisor—and a partnership was born. Together, the two groups worked for years to understand the key factors that contribute to jellyfish propulsion, including the arrangement of their muscles, how their bodies contract and recoil, and how fluid-dynamic effects help or hinder their movements. Once these functions were well understood, the researchers began to design the artificial jellyfish.    

Nawroth and colleagues looked at several materials from which to fashion the body of their beast, eventually settling on an elastic material that is relatively similar to the "jelly" found in a real jellyfish. The team at Harvard—with the help of Nawroth, who spent time on both campuses during the length of the project—fashioned the silicone polymer that makes up the body of the Medusoid into a thin membrane that resembles a small jellyfish, with eight arm-like appendages. Next, they printed a pattern made of protein onto the membrane that resembled the muscle architecture in the real animal. The protein pattern serves as a road map for growth and organization of dissociated rat tissue—individual heart muscle cells that retain the ability to contract—into a coherent swimming muscle.

When the researchers set their creation free in an electrically conducting container of fluid and oscillated the voltage from zero volts to five, they shocked the Medusoid into swimming with synchronized contractions that mimic those of real jellyfish. In fact, the muscle cells started to contract a bit on their own even before the electrical current was applied.

"I was surprised that with relatively few components—a silicone base and cells that we arranged—we were able to reproduce some pretty complex swimming and feeding behaviors that you see in biological jellyfish," says Dabiri, with fluid-dynamics measurements that match up to those of the real animal. "I'm pleasantly surprised at how close we are getting to matching the natural biological performance, but also that we're seeing ways in which we can probably improve on that natural performance. The process of evolution missed a lot of good solutions."

This advance in bio-inspired engineering, the team says, demonstrates that it is inadequate to simply mimic nature: the focus must be on function. Their design strategy, they say, will be broadly applicable to the reverse engineering of muscular organs in humans. In addition, Dabiri and colleagues say, their new process of harvesting heart-muscle cells from one organism and reorganizing them in an artificial system will be useful in building an engineered system using biological materials.

"As engineers, we are very comfortable with building things out of steel, copper, concrete," says Parker. "I think of cells as another kind of building substrate, but we need rigorous quantitative design specs to move tissue engineering from arts and crafts to a reproducible type of engineering. The jellyfish provides a design algorithm for reverse engineering an organ's function and developing quantitative design and performance specifications. We can complete the full exercise of the engineer's design process: design, build, and test."

The team's next goal is to design a completely self-contained system that is able to sense and actuate on its own using internal signals, as human hearts do. Nawroth and Dabiri would also like for the Medusoid to be able to go out and gather food on its own. Then, researchers could think about systems that could live in the human body for years at a time without having to worry about batteries because the system would be able to fend for itself. For example, these systems could be the basis for a pacemaker made with biological elements.

"We're reimagining how much we can do in terms of synthetic biology," says Dabiri. "A lot of work these days is done to engineer molecules, but there is much less effort to engineer organisms. I think this is a good glimpse into the future of re-engineering entire organisms for the purposes of advancing biomedical technology. We may also be able to engineer applications where these biological systems give us the opportunity to do things more efficiently, with less energy usage."

Other Harvard collaborators who contributed to the Nature Biotechnology paper, "A Tissue-Engineered Jellyfish with Biomimetic Propulsion," are Hyungsuk Lee, Adam W. Feinberg, Crystal M. Ripplinger, Megan L. McCain, and Anna Grosberg, who earned her PhD in bioengineering at Caltech. Funding for the study included grants from the Wyss Institute for Biologically Inspired Engineering at Harvard, the National Science Foundation (NSF), the National Institutes of Health, the Office of Naval Research, and NSF Program in Fluid Dynamics.

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Caltech Students Work on Proposed Space Mission for Final Project

Forget problem sets and exams. For their homework and final assignments, students in Caltech's Aerospace Engineering course (Ae105) work on a proposed space mission. For the past few years, students in the class have helped design, prototype, and test various pieces of AAReST, a space-telescope demonstration mission currently under development.

"It's really different from all of our other classes," says graduate student Manan Arya, who took the course this year. "You're actually doing work that's going to go into space. It's really exciting."

Space-based optical telescopes with large primary mirrors or lenses hold promise for expanding human knowledge of Earth and the universe. Larger primary optics allow telescopes to gather more light, and therefore, to peer farther into the cosmos. Currently, the push is to develop space-based telescopes with primary optics larger than 10 meters in diameter (in comparison, the Hubble Space Telescope's primary mirror has a diameter of 2.4 meters). At the moment, though, the size of the mirrors is limited by the diameter of their launch vehicles. One way around the problem? Launch many small, independent spacecraft, each outfitted with its own mirror. Once in orbit, these craft would reconfigure themselves into a single large, segmented aperture.

AAReST (Autonomous Assembly of a Reconfigurable Space Telescope) is a low-cost mission intended to demonstrate the feasibility of this concept. Now in the pre-mission phase, AAReST has a projected launch date of 2015.

Seizing the opportunity to give students some hands-on experience, Sergio Pellegrino, Caltech's Joyce and Kent Kresa Professor of Aeronautics and professor of civil engineering, who is also a senior research scientist at the Jet Propulsion Laboratory (JPL), worked the mission into the Ae105 curriculum. His partners in this effort are JPL engineers Behcet Acikmese, Greg Davis, and Yunjin Kim. The year-long course they devised is fairly traditional for the first term and a half, and then switches to a project-based course to fill out the year.

Recently, this year's students presented the results of their final projects, which involved everything from designing and testing a new method for deploying the spacecraft boom to developing an algorithm to correct the telescope's focusing errors. Prior to the presentations, Pellegrino praised the students for their hard work and creativity. "They have moved the mission forward by a huge step this year, and I thank them for this," he said.

The efforts of the Ae105 students provide a burst of energy for the team that works on AAReST during the rest of the year, Pellegrino says. In past years, the class devised a completely new configuration for the spacecraft; this year, they refined it. "The initial concept has been transformed by the students' input," Pellegrino says.

In addition to being advised by the instructors, the students are mentored by several former Ae105 students and other JPL employees. One of Manan's mentors was retired JPLer Jim Breckinridge, who managed the team that built the camera that corrected the Hubble Space Telescope's originally flawed vision.

"When somebody has that much experience, and they're right next to you on the experimental setup, helping you out one-on-one—that's a rare opportunity," Manan says. "And it's a lot of fun."

The AAReST mission is a collaborative effort between Caltech, JPL, and the University of Surrey, in England. The pre-mission's project manager is JPL's John Baker. The Ae105 class has received funding from the Keck Institute for Space Studies, Caltech's Division of Engineering and Applied Science, and the Innovation in Education Fund, which was made possible in part by the Caltech Associates.

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SEM Honors Rosakis

The Society for Experimental Mechanics (SEM) has selected Ares Rosakis as the recipient of the P.S. Theocaris Award. Rosakis is Caltech's Theodore von Karman Professor of Aeronautics, professor of mechanical engineering, and chair of the Division of Engineering and Applied Science.

The award is intended "to recognize a senior individual for distinguished, innovative and outstanding work in optical methods and experimental mechanics."

In a letter to Rosakis, the chair of the SEM Honors Committee, Kristin Zimmerman, wrote, "Your selection is a well-deserved public statement by your peers of the quality and practicality of your professional contributions."

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The Physics of Going Viral

Caltech researchers measure the rate of DNA transfer from viruses to bacteria

PASADENA, Calif.—Researchers at the California Institute of Technology (Caltech) have been able, for the first time, to watch viruses infecting individual bacteria by transferring their DNA, and to measure the rate at which that transfer occurs. Shedding light on the early stages of infection by this type of virus—a bacteriophage—the scientists have determined that it is the cells targeted for infection, rather than the amount of genetic material within the viruses themselves, that dictate how quickly the bacteriophage's DNA is transferred.

"The beauty of our experiment is we were able to watch individual viruses infecting individual bacteria,"says Rob Phillips, the Fred and Nancy Morris Professor of Biophysics and Biology at Caltech and the principal investigator on the new study. "Other studies of the rate of infection have involved bulk measurements. With our methods, you can actually watch as a virus shoots out its DNA."

The new methods and results are described in a paper titled "A Single-Molecule Hershey–Chase Experiment," which will appear in the July 24 issue of the journal Current Biology and currently appears online. The lead authors of that paper, David Van Valen and David Wu, completed the work while graduate students in Phillips's group.

In the well-known 1952 Hershey-Chase experiment, Alfred Hershey and Martha Chase of the Carnegie Institution of Washington in Cold Spring Harbor convincingly confirmed earlier claims that DNA—and not protein—was the genetic material in cells. To prove this, the researchers used bacteriophages, which are able to infect bacteria using heads of tightly bundled DNA coated in a protein shell. Hershey and Chase radiolabeled sulfur, contained in the protein shell but not in the DNA, and phosphorous, found in the DNA but not in the protein shell. Then they let the bacteriophages infect the bacterial cells. When they isolated the cells and analyzed their contents, they found that only the radioactive phosphorous had made its way into the bacteria, proving that DNA is indeed the genetic material. The results also showed that, unlike the viruses that infect humans, bacteriophages transmit only their genetic information into their bacterial targets, leaving their "bodies" behind.

"This led, right from the get-go, to people wondering about the mechanism—about how the DNA gets out of the virus and into the infected cell," Phillips says. Several hypotheses have focused on the fact that the DNA in the virus is under a tremendous amount of pressure. Indeed, previous work has shown that the genetic material is under more pressure within its protein shell than champagne experiences in a corked bottle. After all, as Phillips says, "There are 16 microns of DNA inside of a tiny 0.05 micron-sized shell. It's like taking 500 meters of cable from the Golden Gate Bridge and putting it in the back of a FedEx truck." 

Phillips's group wanted to find out whether that pressure plays a dominant role in transferring the DNA. Instead, he says, "What we discovered is that the thing that mattered most was not the pressure in the bacteriophage, but how much DNA was in the bacterial cell."

The researchers used a fluorescent dye to stain the DNA of two mutants of a bacteriophage known as lambda bacteriophage—one with a short genome and one with a longer genome—while that DNA was still inside the phage. Using a fluorescence microscope, they traced the glowing dye to see when and over what time period the viral DNA transferred from each phage into an E. coli bacterium. The mean ejection time was about five minutes, though that time varied considerably.

This was markedly different from what the group had seen previously when they ran a similar experiment in a test tube. In that earlier setup, they had essentially tricked the bacteriophages into ejecting their DNA into solution—a task that the phages completed in less than 10 seconds. In that case, once the phage with the longer genome had released enough DNA to make what remained inside the phage equal in length to the shorter genome, the two phages ejected DNA at the same rate. Therefore, Phillips's team reasoned, it was the amount of DNA in the phage that determined how quickly the DNA was transferred.

But Phillips says, "What was true in the test tube is not true in the cell." E. coli cells contain roughly 3 million proteins within a box that is roughly one micron on each side. Less than a hundredth of a micron separates each protein from its neighbors. "There's no room for anything else," Phillips says. "These cells are really crowded." 

And so, when the bacteriophages try to inject their DNA into the cells, the factor that limits the rate of transfer is how jam-packed those cells are. "In this case," Phillips says, "it had more to do with the recipient, and less to do with the pressure that had built up inside the phage."

Looking toward the future, Phillips is interested in using the methods he and his team have developed to study different types of bacteriophages. He also wants to investigate various molecules that could be helping to actively pull the viral DNA into the cells. In the case of a bacteriophage called T7, for instance, previous work has shown that the host cell actually grabs onto the DNA and begins making copies of its genes before the virus has even delivered all the DNA into the cell. "We're curious whether that kind of mechanism is in play with the lambda bacteriophage," Phillips says.

The current findings have implications for the larger question of how biomolecules like DNA and proteins cross membranes in general, and not just into bacteria. Cells are full of membranes that divide them into separate compartments and that separate entire cells from the rest of the world. Much of the business of cellular life involves getting molecules across those barriers. "This process that we've been studying is one of the most elementary examples of what you could call polymer translocation or getting macromolecules across membranes," Phillips says. "We are starting to figure out the physics behind that process."

In addition to Phillips, Van Valen, and Wu, the other authors on the Current Biology paper are graduate student Yi-Ju Chen; Hannah Tuson of the University of Wisconsin at Madison; and Paul Wiggins of the University of Washington. Van Valen is currently a medical student at UCLA's David Geffen School of Medicine, and Wu is an intern at the University of Chicago. The work was supported by funding from the National Science Foundation, a National Institutes of Health Medical Scientist Training Program fellowship, a Fannie and John Hertz Yaser Abu-Mostafa Graduate Fellowship, and an NIH Director's Pioneer Award.

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Seeing Inside Tissue

Caltech researchers develop technique to focus light inside biological tissue

PASADENA, Calif.—Imagine if doctors could perform surgery without ever having to cut through your skin. Or if they could diagnose cancer by seeing tumors inside the body with a procedure that is as simple as an ultrasound. Thanks to a technique developed by engineers at the California Institute of Technology (Caltech), all of that may be possible in the not-so-distant future.

The new method enables researchers to focus light efficiently inside biological tissue. While the previous limit for how deep light could be focused was only about one millimeter, the Caltech team is now able to reach two and a half millimeters. And, in principle, their technique could focus light as much as a few inches into tissue. The technique is used much like a flashlight shining on the body's interior, and may eventually provide researchers and doctors with a host of possible biomedical applications, such as a less invasive way of diagnosing and treating diseases.

If you crank up the power of light, you might even be able to do away with a traditional scalpel. "It enables the possibilities of doing incision-less surgery," says Changhuei Yang, a professor of electrical engineering and bioengineering at Caltech and a senior author on the new study. "By generating a tight laser-focus spot deep in tissue, we can potentially use that as a laser scalpel that leaves the skin unharmed."

Ying Min Wang, a graduate student in electrical engineering, and Benjamin Judkewitz, a postdoctoral scholar, are the lead authors on the paper, which was published in the June 26 issue of the journal Nature Communications.

The new work builds on a previous technique that Yang and his colleagues developed to see through a layer of biological tissue, which is opaque because it scatters light. In the previous work, the researchers shined light through the tissue and then recorded the resulting scattered light on a holographic plate. The recording contained all the information about how the light beam scattered, zigzagging through the tissue. By playing the recording in reverse, the researchers were able to essentially send the light back through to the other side of the tissue, retracing its path to the original source. In this way, they could send light through a layer of tissue without the blurring effect of scattering.

But to make images of what is inside tissue—to get a picture of cells or molecules that are embedded inside, say, a muscle—the researchers would have to be able to focus a light beam into the tissue. "For biologists, it's most important to know what's happening inside the tissue," Wang says.

To focus light into tissue, the researchers expanded on the recent work of Lihong Wang's group at Washington University in St. Louis (WUSTL); they had developed a method to focus light using the high-frequency vibrations of ultrasound. The WUSTL group took advantage of two properties of ultrasound. First, the high-frequency sound waves are not scattered by tissue, which is why it is great for taking images of fetuses in utero. Second, ultrasonic vibrations interact with light in such a way that they shift the light's frequency ever so slightly. As a result of this so-called acousto-optic effect, any light that has interacted with ultrasound changes into a slightly different color.

In both the WUSTL and Caltech experiments, the teams focused ultrasound waves into a small region inside a tissue sample. They then shined light into the sample, which, in turn, scattered the light. Because of the acousto-optic effect, any of the scattered light that passes through the region with the focused ultrasound will change to a slightly different color. The researchers can pick out this color-shifted light and record it. By employing the same playback technique as in the earlier Caltech work, they then send the light back, having only the color-shifted bits retrace their path to the small region where the ultrasound was focused—which means that the light itself is focused on that area, allowing an image to be created. The researchers can control where they want to focus the light simply by moving the ultrasound focus.

The WUSTL experiment was limited, however, because only a very small amount of light could be focused. The Caltech engineers' new method, on the other hand, allows them to fire a beam of light with as much power as they want—which is essential for potential applications. 

The team demonstrated how the new method could be used with fluorescence imaging—a powerful technique used in a wide range of biological and biomedical research. The researchers embedded a patch of gel with a fluorescent pattern that spelled out "CIT" inside a tissue sample. Then, they scanned the sample with focused light beams. The focused light hit and excited the fluorescent pattern, resulting in the glowing letters "CIT" emanating from inside the tissue. The team also demonstrated their technique by taking images of tumors tagged with fluorescent dyes.

"This demonstration that we can focus significant optical power deep within tissues opens up significant possibilities in optical imaging," Yang says. By tagging cells or molecules that are markers for disease with fluorescent dyes, doctors can use this technique to make diagnoses noninvasively, much as if they were doing an ultrasound procedure.

Doctors might also use this process to treat cancer with photodynamic therapy. In this procedure, a drug that contains light-sensitive, cancer-killing compounds is injected into a patient. Cancer cells absorb those compounds preferentially, so that the compounds kill the cells when light shines on them. Photodynamic therapy is now only used at tissue surfaces, because of the way light is easily scattered. The new technique should allow doctors to reach cancer cells deeper inside tissue.

The team has been able to more than double the current limit for how far light can be focused into tissue. With future improvements on the optoelectronic hardware used to record and play back light, the engineers say, they may be able to reach 10 centimeters (almost 4 inches)—the depth limit of ultrasound—within a few years.

Still, the researchers say, their demonstration shows they have overcome the main conceptual hurdle for effectively focusing light deep inside tissue. "This is a big breakthrough, and we're excited about the potential," Judkewitz says. Adds Caltech's Wang, "It's a very new way to image into tissue, which could lead to a lot of promising applications."

The Nature Communications paper is titled "Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light." In addition to Wang, Judkewitz, and Yang, the other author on the paper is Charles DiMarzio of Northeastern University. This work was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, the Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust, and the National Science Scholarship from the Agency for Science, Technology, and Research in Singapore.

Written by Marcus Woo

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Caltech Rover Team Wins Second Place in Robo-Ops Competition

After designing and building a four-wheeled remotely controlled rover, a team of Caltech students came away with second place in the RASC-AL Exploration Robo-Ops Competition at NASA's Johnson Space Center earlier this month. Despite a weather delay and some wayward sand, the robot operated as designed and managed to traverse different slopes and types of terrain in Johnson's Rock Yard, picking up four rock targets and an "alien" during the one-hour roving portion of the competition.

"All in all, the competition was a great success," says Justin Koch, the mobility system lead for the Caltech Rover Team and a mechanical engineering major who just completed his first year at Caltech. "Everyone on the team put in a lot of hours, and the quality of the rover demonstrated that it was time well spent." 

The Revolutionary Aerospace Systems Concepts Academic Linkage (RASC-AL) Exploration Robo-Ops Competition challenges teams of university students with the engineering task of designing and building a planetary rover prototype. Sponsored by NASA and organized by the National Institute of Aerospace, the competition gives students the opportunity to apply what they have learned in the classroom to a real-world problem. 

Caltech and seven other teams were selected as finalists based on written proposals submitted in December. Each team received $10,000 to build a rover and to send three team members and an advisor—in Caltech's case, that was Joel Burdick, professor of mechanical engineering and bioengineering—to the competition forum in Houston, which took place May 30 through June 1. The remaining members of each team stayed at their home institution to remotely operate their rovers. Thanks to a live video feed and the 4G network, the majority of Caltech's team was able to watch and control the rover's every move from "mission control" in the basement of Spalding Laboratory. 

During the roving portion of the competition, which accounted for 60 percent of the final score, each team had free rein on the course for one hour. The Caltech Rover Team started its run on May 31. They managed to pick up two colored target rocks in the sand pit, but ran into some problems with grains of sand getting into the joints of the rover arm's gripper. They used the five-minute "mulligan" every team gets to repair the rover, but the run was later interrupted by an approaching thunderstorm. 

They resumed their run the following day, navigating from the sand pit to the "lunar craters," where they found and picked up an "alien" toy. Before their hour of roving was up, they collected two additional rocks on the hill. 

"The roving portion of the competition at Houston was exciting to say the least," says rising junior Daniel Lo, the leader and organizer of Caltech's team and a physics and planetary science double major. "We encountered difficulties, things we did not expect, but I am really proud that as a team we persisted."

Out of a possible 60 points, the Caltech team received 39 for the roving portion of the competition. The first-place winners, Worcester Polytechnic University, earned the full 60 points, while the third-place team, from the University of Maryland, picked up six points. Teams were also judged on a technical paper, an oral poster presentation, and an education and public-outreach component.

For their second-place performance, the Caltech Rover Team received $4,000, which they plan to use on future robotics competitions. They also received a good-sportsmanship award for loaning their tools and duct tape to the University of Pennsylvania team when its rover broke down. Koch says the experience he gained was worth the time and effort. "I picked up a lot of hands-on knowledge that will be useful for future projects," he says.

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