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Thursday, March 13th, 2014

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    5:00a
    Soft robotic fish moves like the real thing
    Soft robots — which don’t just have soft exteriors but are also powered by fluid flowing through flexible channels — have become a sufficiently popular research topic that they now have their own journal, Soft Robotics. In the first issue of that journal, out this month, MIT researchers report the first self-contained autonomous soft robot capable of rapid body motion: a “fish” that can execute an escape maneuver, convulsing its body to change direction in just a fraction of a second, or almost as quickly as a real fish can.

    “We’re excited about soft robots for a variety of reasons,” says Daniela Rus, a professor of computer science and engineering, director of MIT’s Computer Science and Artificial Intelligence Laboratory, and one of the researchers who designed and built the fish. “As robots penetrate the physical world and start interacting with people more and more, it’s much easier to make robots safe if their bodies are so wonderfully soft that there’s no danger if they whack you.”

    Another reason to study soft robots, Rus says, is that “with soft machines, the whole robotic planning problem changes.” In most robotic motion-planning systems, avoiding collisions with the environment is the highest priority. That frequently leads to inefficient motion, because the robot has to settle for collision-free trajectories that it can find quickly.

    With soft robots, collision poses little danger to either the robot or the environment. “In some cases, it is actually advantageous for these robots to bump into the environment, because they can use these points of contact as means of getting to the destination faster,” Rus says.

    But the new robotic fish was designed to explore yet a third advantage of soft robots: “The fact that the body deforms continuously gives these machines an infinite range of configurations, and this is not achievable with machines that are hinged,” Rus says. The continuous curvature of the fish’s body when it flexes is what allows it to change direction so quickly. “A rigid-body robot could not do continuous bending,” she says.

    Escape velocity

    The robotic fish was built by Andrew Marchese, a graduate student in MIT’s Department of Electrical Engineering and Computer Science and lead author on the new paper, where he’s joined by Rus and postdoc Cagdas D. Onal. Each side of the fish’s tail is bored through with a long, tightly undulating channel. Carbon dioxide released from a canister in the fish’s abdomen causes the channel to inflate, bending the tail in the opposite direction.

    Each half of the fish tail has just two control parameters: the diameter of the nozzle that releases gas into the channel and the amount of time it’s left open. In experiments, Marchese found that the angle at which the fish changes direction — which can be as extreme as 100 degrees — is almost entirely determined by the duration of inflation, while its speed is almost entirely determined by the nozzle diameter. That “decoupling” of the two parameters, he says, is something that biologists had observed in real fish.

    “To be honest, that’s not something I designed for,” Marchese says. “I designed for it to look like a fish, but we got the same inherent parameter decoupling that real fish have.”


    That points to yet another possible application of soft robotics, Rus says, in biomechanics. “If you build an artificial creature with a particular bio-inspired behavior, perhaps the solution for the engineered behavior could serve as a hypothesis for understanding whether nature might do it in the same way,” she says.

    Marchese built the fish in Rus’ lab, where other researchers are working on printable robotics. He used the lab’s 3-D printer to build the mold in which he cast the fish’s tail and head from silicone rubber and the polymer ring that protects the electronics in the fish’s guts.

    The long haul

    The fish can perform 20 or 30 escape maneuvers, depending on their velocity and angle, before it exhausts its carbon dioxide canister. But the comparatively simple maneuver of swimming back and forth across a tank drains the canister quickly. “The fish was designed to explore performance capabilities, not long-term operation,” Marchese says. “Next steps for future research are taking that system and building something that’s compromised on performance a little bit but increases longevity.”

    A new version of the fish that should be able to swim continuously for around 30 minutes will use pumped water instead of carbon dioxide to inflate the channels, but otherwise, it will use the same body design, Marchese says. Rus envisions that such a robot could infiltrate schools of real fish to gather detailed information about their behavior in the natural habitat.

    “All of our algorithms and control theory are pretty much designed with the idea that we’ve got rigid systems with defined joints,” says Barry Trimmer, a biology professor at Tufts University who specializes in biomimetic soft robots. “That works really, really well as long as the world is pretty predictable. If you’re in a world that is not — which, to be honest, is everywhere outside a factory situation — then you start to lose some of your advantage.”

    The premise of soft robotics, Trimmer says, is that “if we learn how to incorporate all these other sorts of materials whose response you can’t predict exactly, if we can learn to engineer that to deal with the uncertainty and still be able to control the machines, then we’re going to have much better machines.”

    The MIT researchers’ robot fish “is a great demonstration of that principle,” Trimmer says. “It’s an early stage of saying, ‘We know the actuator isn’t giving us all the control we’d like, but can we actually still exploit it to get the performance we want?’ And they’re able to show that yes, they can.”
    5:00p
    New view of tumors’ evolution
    Cancer cells undergo extensive genetic alterations as they grow and spread through the body. Some of these mutations, known as “drivers,” help spur cells to grow out of control, while others (“passengers”) are merely along for the ride.

    MIT cancer biologists at the Koch Institute for Integrative Cancer Research and geneticists from the Broad Institute have now performed the most comprehensive analysis to date of these changes in mice programmed to develop cancer. The team discovered mutations and other genetic disturbances that arise at certain stages of lung cancer development; the researchers were also able to identify tumor cells that broke free to spread to other organs.

    The findings, described in the March 13 issue of Cell, suggest possible new targets for drugs for this aggressive form of cancer, known as small cell lung cancer. There are now very few targeted drugs for small cell lung cancer, a highly lethal form of lung cancer that is associated with tobacco use and is usually treated with chemotherapy drugs that have severe side effects.

    “Right now, small cell lung cancer is really lagging behind with respect to therapies that target a specific mutation or genetic alteration in the tumors, because we don’t know a lot about the drivers in these cancers,” says David McFadden, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and one of the lead authors of the Cell paper.

    Other lead authors of the paper are Koch Institute postdoc Thales Papagiannakopoulos and Broad Institute researchers Amaro Taylor-Weiner, Chip Stewart, and Scott Carter. Senior authors are Tyler Jacks, the David H. Koch Professor of Biology and director of the Koch Institute, and Gad Getz, director of cancer genome computational analysis at the Broad Institute and director of the bioinformatics program at Massachusetts General Hospital.

    Tracking cancer progression

    The research team studied a strain of mice that lacks two key tumor-suppressor genes, p53 and Rb. These mice develop small cell lung cancer, but scientists don’t know exactly how the cancer progresses or which subsequent genetic alterations drive tumor growth.

    In studies of human small cell lung cancer, it has been difficult to identify these driver mutations because potent carcinogens in cigarette smoke produce many mutations, most of which don’t affect tumor growth. In the mouse model of the disease, fewer mutations arise because the mice are not exposed to cigarette smoke, making it easier to identify the key drivers.

    Mice lacking p53 and Rb, the two most commonly mutated tumor suppressors in human small cell lung cancer, develop lung tumors that closely mimic the progression of human small cell lung cancer. These tumors are highly metastatic and usually spread to the lymph nodes near the lungs and then to the liver. The researchers isolated DNA from these tumors and analyzed the genetic alterations that occurred, including genetic mutations as well as changes in the number of copies of a gene or chromosome.

    First, the researchers compared genetic alterations that appeared early and late in cancer development. They found that early on, tumors accumulate many extra copies of a gene called Mycl1, a known oncogene that helps cells ignore signals to stop growing. Because Mycl1 is mutated so early, it is found in nearly all of the tumor cells, making it a good drug target, McFadden says. There are currently no cancer treatments that specifically target Mycl1, but scientists are now working on drugs that target a closely related oncogene, MYC.

    Later in tumor progression, the mouse cancer cells lose a gene called Pten, which has previously been found mutated in about 20 percent of small cell lung cancer patients. In normal cells, Pten regulates a critical signaling pathway called PI3K, which influences many aspects of cell growth and survival. When Pten is lost, the pathway becomes overactive, allowing tumor cells to grow very rapidly.

    Drugs that target the PI3K pathway are now in the early stages of clinical testing in human patients.

    Retracing metastasis

    The researchers also compared the genomes of cells from the original lung tumors and from tumors that later appeared in other sites. This enabled them to retrace the tumor cells’ paths and to determine which lung tumors were the sources of the metastases. They found that while multiple subsets of cells from the lung tumors could move to the lymph nodes, usually only a single subset from the lymph nodes spread to the liver.

    “Our data really add to this emerging idea that metastatic spread is quite complicated, and that there may be different populations within a single cancer moving around to different sites, which may complicate treatments,” McFadden says.

    The approach taken by the MIT and Broad team offers a unique opportunity to study the mechanisms that underlie lung cancer development and spread, says Anton Berns, a research group leader at the Netherlands Cancer Institute.

    “This is of interest, as it can reveal that there might or might not be a specific route, and that there is a specific order in which selections for mutations do take place. In this regard this is a landmark paper,” says Berns, who was not part of the research team. “It is a beautiful, detailed dissection of tumor development in the mouse, carefully executed with great attention for what such a system can teach.”

    The researchers now hope to perform further genetic analysis to identify which mutations make certain cells more likely to metastasize. They also plan to try treating small cell lung tumors with chemotherapy drugs and observing the genetic changes that occur as cancer cells become resistant to treatment.

    The study was funded by the Ludwig Center for Molecular Oncology at MIT, the Howard Hughes Medical Institute, the National Human Genome Research Institute, a National Institutes of Health-National Cancer Institute Career Development Award, and a Hope Funds for Cancer Research Fellowship.
    8:00p
    AeroAstro professor David Miller named NASA’s chief technologist
    NASA has named David W. Miller, the Jerome C. Hunsaker Professor of Aeronautics and Astronautics at MIT, as its new chief technologist. He will be NASA’s principal advisor and advocate on technology policy and programs.

    “David’s passion for discovery and innovation is a valuable asset as we move forward into exploring new frontiers,” NASA Administrator Charles Bolden said in announcing the appointment. “He has challenged his students to create new ways to operate in space. I expect he will challenge us to do the same. His experience in engineering space systems, small satellites, and long-duration microgravity platforms will allow him to offer the kind of expert advice I have learned to expect from my chief technologists.”

    The Office of the Chief Technologist is responsible for coordinating and tracking NASA technology investments, as well as developing and executing innovative technology partnerships, technology transfers, and commercial activities, and the development of collaboration models for the agency.

    Miller has stepped down from his position as director of MIT’s Space Systems Laboratory (SSL) to accept the NASA appointment. During his tenure at NASA, Miller will keep his MIT faculty position and will continue as a student advisor.

    As SSL director, Miller has played a role in many NASA projects. He was principal investigator for MIT’s Regolith X-ray Imaging Spectrometer, which is an element of NASA’s OSIRIS-REx asteroid sample return mission planned for launch in 2016. He was also the principal investigator for the SPHERES microsatellite project, which is currently aiding research aboard the International Space Station. Miller has also served as vice chairman of the Air Force Scientific Advisory Board.

    Miller has been on the MIT faculty since 1997. His work has focused on developing special spacecraft that can repair and upgrade other spacecraft and satellites in space. He participated in developing electromagnetic formation flight, which is the use of electromagnets coupled with reaction wheels to control the positions and attitudes of multiple spacecraft in proximity to each other.

    He has also been a leader of AeroAstro’s capstone class, where seniors apply the conceiving, designing, implementing, and operating skills they have learned in the department to a project. The SPHERES microsatellites were conceived by students under his supervision in the capstone class.

    “Dave has taken AeroAstro classes to a new level, working with both undergrads and grad students on real projects for real customers with real deliveries,” says AeroAstro department head Jaime Peraire, the H.N. Slater Professor of Aeronautics and Astronautics. “He has unparalleled vision and understanding of aerospace systems, and this, coupled with his ability to focus large, diverse groups on complex projects, underscores what an excellent choice NASA has made for its chief technologist.”

    AeroAstro has a long history of faculty taking leading roles in government policy and technology leadership. Its current community includes a former secretary of the Air Force, a NASA associate administrator, and an Air Force chief scientist.

    The Jerome C. Hunsaker Professorship is named for the founder of MIT’s, and the nation’s, first aeronautics course in 1914. Hunsaker later became head of MIT’s aeronautical engineering department.

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