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Tuesday, February 7th, 2017

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    2:30p
    Nanoparticle screen could speed up drug development

    Many scientists are pursuing ways to treat disease by delivering DNA or RNA that can turn a gene on or off. However, a major obstacle to progress in this field has been finding ways to safely deliver that genetic material to the correct cells.

    Encapsulating strands of RNA or DNA in tiny particles is one promising approach. To help speed up the development of such drug-delivery vehicles, a team of researchers from MIT, Georgia Tech, and the University of Florida has now devised a way to rapidly test different nanoparticles to see where they go in the body.

    “Drug delivery is a really substantial hurdle that needs to be overcome,” says James Dahlman, a former MIT graduate student who is now an assistant professor at Georgia Tech and the study’s lead author. “Regardless of their biological mechanisms of action, all genetic therapies need safe and specific drug delivery to the tissue you want to target.”

    This approach, described in the Proceedings of the National Academy of Sciences the week of Feb. 6, could help scientists target genetic therapies to precise locations in the body.

    “It could be used to identify a nanoparticle that goes to a certain place, and with that information we could then develop the nanoparticle with a specific payload in mind,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

    The paper’s senior authors are Anderson; Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute; and Eric Wang, a professor at the University of Florida. Other authors are graduate student Kevin Kauffman, recent MIT graduates Yiping Xing and Chloe Dlott, MIT undergraduate Taylor Shaw, and Koch Institute technical assistant Faryal Mir.

    Targeting disease

    Finding a reliable way to deliver DNA to target cells could help scientists realize the potential of gene therapy — a method of treating diseases such as cystic fibrosis or hemophilia by delivering new genes that replace missing or defective versions. Another promising approach for new therapies is RNA interference, which can be used to turn off overactive genes by blocking them with short strands of RNA known as siRNA.

    Delivering these types of genetic material into body cells has proven difficult, however, because the body has evolved many defense mechanisms against foreign genetic material such as viruses.

    To help evade these defenses, Anderson’s lab has developed nanoparticles, including many made from fatty molecules called lipids, that protect genetic material and carry it to a particular destination. Many of these particles tend to accumulate in the liver, in part because the liver is responsible for filtering blood, but it has been more difficult to find particles that target other organs.

    “We’ve gotten good at delivering nanoparticles into certain tissues but not all of them,” Anderson says. “We also haven’t really figured out how the particles’ chemistries influence targeting to different destinations.”

    To identify promising candidates, Anderson’s lab generates libraries of thousands of particles, by varying traits such as their size and chemical composition. Researchers then test the particles by placing them on a particular cell type, grown in a lab dish, to see if the particles can get into the cells. The best candidates are then tested in animals. However, this is a slow process and limits the number of particles that can be tried.

    “The problem we have is we can make a lot more nanoparticles than we can test,” Anderson says.

    To overcome that hurdle, the researchers decided to add “barcodes,” consisting of a DNA sequence of about 60 nucleotides, to each type of particle. After injecting the particles into an animal, the researchers can retrieve the DNA barcodes from different tissues and then sequence the barcodes to see which particles ended up where.

    “What it allows us to do is test many different nanoparticles at once inside a single animal,” Dahlman says.

    Tracking particles

    The researchers first tested particles that had been previously shown to target the lungs and the liver, and confirmed that they did go where expected. 

    Then, the researchers screened 30 different lipid nanoparticles that varied in one key trait — the structure of a component known as polyethylene glycol (PEG), a polymer often added to drugs to increase their longevity in the bloodstream. Lipid nanoparticles can also vary in their size and other aspects of their chemical composition.

    Each of the particles was also tagged with one of 30 DNA barcodes. By sequencing barcodes that ended up in different parts of the body, the researchers were able to identify particles that targeted the heart, brain, uterus, muscle, kidney, and pancreas, in addition to liver and lung. In future studies, they plan to investigate what makes different particles zero in on different tissues.

    The researchers also performed further tests on one of the particles, which targets the liver, and found that it could successfully deliver siRNA that turns off the gene for a blood clotting factor.

    Victor Koteliansky, director of the Skoltech Center for Functional Genomics, described the technique as an “innovative” way to speed up the process of identifying promising nanoparticles to deliver RNA and DNA.

    “Finding a good particle is a very rare event, so you need to screen a lot of particles. This approach is faster and can give you a deeper understanding of where particles will go in the body,” says Kotelianksy, who was not involved in the research.

    This type of screen could also be used to test other kinds of nanoparticles such as those made from polymers. “We’re really hoping that other labs across the country and across the world will try our system to see if it works for them,” Dahlman says.

    The research was funded by an MIT Presidential Fellowship, a National Defense Science and Engineering Graduate Fellowship, a National Science Foundation Graduate Research Fellowship, the MIT Undergraduate Research Opportunities Program, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, and the National Institutes of Health.

    4:00p
    New faculty strengthen, broaden MIT’s energy expertise

    From mimicking the natural characteristics of photosynthesis in human-made solar energy systems, to modeling plasma behavior in fusion reactor designs, some of MIT's newest faculty bring a wide array of energy expertise to the Institute. The latest issue of the MIT Energy Initiative (MITEI) magazine, Energy Futures, gives an in-depth look at what drives four of them.

    Gabriela Schlau-Cohen: What photovoltaics can learn from photosynthesis

    Unlike human-made electric grids, the natural world’s energy-harvesting systems never experience blackouts. Gabriela Schlau-Cohen, assistant professor of chemistry at MIT, is trying to learn from this natural talent for energy-making so she can change our energy systems for the better.

    For Schlau-Cohen, this means starting with plants. Plants are the ultimate energy-users: The average global rate of photosynthesis is 130 terawatts — a level of energy-capture more than six times worldwide energy consumption. “Leaves absorb light throughout the visible spectrum, and they basically funnel all of that energy to a dedicated protein where electricity is generated,” Schlau-Cohen says. Plants’ ability to convert sunlight into electricity is two- to three-fold higher than that of a typical solar photovoltaic (PV) system.

    With this in mind, Schlau-Cohen and her colleagues set out to unlock plants’ energy secrets. They began by studying the basic physics of plants, with the eventual goal of mimicking these natural characteristics in a human-made system. Through the MIT Center for Excitonics, Schlau-Cohen and her team are able to experiment with cutting-edge technology for bio-inspired artificial light-harvesting systems.

    One of the most important takeaways from her study of plants isn’t the discovery of a single plant structure or chemical that makes natural energy processing so efficient, Schlau-Cohen says. It’s the economic choices represented by the operation of the system as a whole.

    “I think that the big picture here is that nature has solved the intermittency problem,” says Schlau-Cohen. One of the major challenges for renewable energy is that two of its key sources — wind and sunlight — are intermittent. That variability proves a challenge for those who are trying to develop technology for harvesting energy from those sources. Schlau-Cohen gives the example of building solar PV systems. “Build a system to handle just the maximum amount of sunlight, and it’s going to sit idle for most of the time,” says Schlau-Cohen. “But build it to work best at the lowest level of sunlight, and in high-sun situations much of the light is unused.”

    To deal with this challenge, the energy-harvesting pathways in plants are designed to strike a balance between being hardy enough to operate in full sunlight and finely tuned enough to make the most of low sunlight conditions. Increasing the amount of time the system can be active has economic advantages as well. Natural systems optimize by making sure their most energy-expensive machinery is always in use so that they can get the most out of it. “Through complicated feedback loops implemented in its molecular machinery, the system responds to changes in solar intensity,” says Schlau-Cohen. This responsiveness addresses the intermittency problem, while also ensuring that the plant structures that take the most energy to develop are used to their full potential.

    Based on their new understanding of plants’ energy-harvesting pathways, Schlau-Cohen and her team are finding ways to control for different variables — creating biomass, for example, rather than protecting the system against too much sunlight. “If we rewire those pathways for optimizing biomass, we can get a 15 percent increase in biomass, or even 30 percent under some conditions,” she says.

    As Schlau-Cohen tackles these issues at the forefront of energy knowledge, she finds a source of inspiration in her research community. When she made the decision to come to MIT, the students were a particular draw. “I think MIT students are the best of the best, not just in terms of their smarts, but in terms of their excitement about science,” she says. “That was something I could not turn down, because I felt like they would make me the best scientist I could be.” The students have not disappointed, providing both inspiration and fun — Schlau-Cohen’s very own source of renewable energy.

    Rafael Jaramillo: Making new materials to energize today’s technologies

    Rafael Jaramillo studied physics as an undergrad and graduate student, but at MIT — first as a postdoc and now as an assistant professor — his work has taken him in a slightly different direction. He’s now developing new materials and teaching materials science and engineering. During his career in engineering, one important lesson he’s learned is how to see new pathways for scientific discoveries that transcend, and often connect, research fields.

    “I try to find where the connections are between the scope of science, what you’re capable of at a university, and what matters for energy applications such as solar photovoltaics,” Jaramillo says. As a postdoc, he worked with Tonio Buonassisi, an MIT professor in mechanical engineering who is an expert in solar photovoltaics. “I really appreciate the real-world education I got in Tonio’s group,” Jaramillo says. “It taught me how to be opportunistic — how to define projects where all of those factors come together, and you can find a way to help.”

    Though photovoltaics isn’t Jaramillo’s only focus now, he’s carried this skill for finding opportunities for discovery throughout his studies and his early professorship. On the energy front, he now specializes in the study of semi­conductors and their use as new materials for improved energy devices, from batteries and microelectronics to photovoltaic systems.

    Jaramillo knows that his interest in semiconductors is something of a departure from his training in fundamental physics. “Physics has in a way moved on,” he says. “It’s been several decades since departments have really taught semiconductors.” This well-studied class of materials, however, is seeing the dawn of a new era. In the low-carbon energy arena, scientists are constantly experimenting with new materials that will improve the economics and energy footprint of existing technologies, permitting critically needed increases in manufacturing along with cost reductions from economies of scale.

    Different materials will address different scaling challenges in areas ranging from solar PV to computing to sustainable global development, but the fact that new materials are needed remains a constant, Jaramillo says. “We’re butting up against the limitations of the tried and true materials. That’s exciting because it means you get to dive in and think about new materials. And they’re all semiconductors.”

    As Jaramillo works to develop new materials, he is also seeking new ways to inspire students to study one of the most classic (and deceptively basic) topics in science: thermo­dynamics, the subject of an introductory course he teaches to undergraduates. “Thermodynamics is almost the core of materials science,” he says. “It allows you to make predictions about how to process materials and get desired products.” This importance, though, is sometimes lost in traditional ways of teaching the subject. “There are canonical examples, like the invention of steel and the invention of stainless steel, but I tend to focus more on microelectronics and semiconductors,” he says. “You can find great canonical examples of thermodynamics in action from not just 60, 70, 80 years back, but in the last 10 years, 20 years, and today. I like to reach for those.”

    According to Jaramillo, it all comes down to being open to new ways of looking at the world, and the applied sciences are a critical part of that. “I think a lot of the great, deep insights have come out of applied research throughout history,” he says. “Einstein came up with relativity by looking at train tables and asking very practical questions about how you synchronize train arrival and departure times across Europe. That sounds pretty boring in the wrong hands. So I think that use-inspired research and going in multiple directions from there is the most rewarding way to do science.”

    David Hsu: Planning cities for sustainable living

    “Climate change, climate change, climate change.” Assistant Professor David Hsu in the Department of Urban Studies and Planning has no hesitation naming what he considers the most significant challenge facing urban planners today. Threats to cities range from sea-level rise to extreme weather events. But for Hsu, the immediate challenge is to address climate change itself by finding ways to make cities and their inhabitants consume resources like energy and water more efficiently.

    Tackling particular sectors can affect climate on a global scale. Hsu says, “If you take just U.S. buildings as a single country, it would be the third-biggest carbon emitter on the planet after the rest of the U.S. economy and China.” Accordingly, a number of Hsu’s current projects involve how to make built environments, both urban and rural, more sustainable. He’s collaborating with fellow researchers at MIT and elsewhere on a wide range of projects including smart infrastructure embedded in physical systems, regulatory policies that promote renewables, and deployment of experimental microgrids in India.

    One of the most effective ways to cut down on building energy use, though, is to target the behavior of those inhabiting the buildings. In order to understand humans’ energy behavior and how to change it, researchers need data. One of Hsu’s new projects involves integrating programs, policies, and technologies to enable the moni­toring of energy flows between buildings and the grid. This setup would enable greater grid stability — a prospect that Hsu and his fellow researchers hope will attract the attention of today’s utilities. That information would also enable researchers to map out energy distribution and consumption, which in turn would help them understand better how to shape that consumption to minimize carbon emissions and energy use, he says. Sometimes, one of the most direct ways to encourage people to consume less is simply to share such data with them. Once consumers see how they’re using energy, they can make informed decisions about where they could make changes.

    Hsu took a self-described “long, tortuous educational path,” one that he laughingly tells students never to replicate. This path led from under­graduate and master’s degrees in physics to a PhD in urban planning and design. His post-graduation jobs ranged from green-building engineering to real estate finance, and eventually brought him to city government. His first job in city planning was in New York City working to rebuild Lower Manhattan after Sept. 11, 2001.

    Since then, Hsu has worked in cities from Philadelphia to Seattle to London. This rich, varied experience with city living has led Hsu to his current focus on human interaction with infrastructure, as well as the challenges involved in adapting infrastructure to emerging climate constraints. Last spring he taught a course called Theories of Infrastructure, which compared alternative theories of how people interact with technological systems. Hsu enjoyed the students as much as the course content. “I had a diverse bunch of students who were really into the topic,” he says. “They were curious, interested, and we had great debates.”

    Hsu’s membership on the MIT Energy Initiative’s Energy Education Task Force demonstrates his commitment to training leaders in all aspects of energy. But he especially focuses on preparing the urban planners of tomorrow to grapple with humans’ relationship with energy — a remarkably varied one, depending on where you live. “In many places, people have never had cheap, safe, and reliable electricity. One or two out of the three, maybe, but never all three,” Hsu says. Providing all three while also encouraging people worldwide to build sustainable ways of life is — in Hsu’s view — one of the great challenges facing city planners today.

    Nuno Loureiro: In search of a more perfect fusion reactor

    Nuno Loureiro, an assistant professor of nuclear science and engineering at MIT, is particularly attuned to the inner movement of complex systems. Much of his research on plasma theory and modeling concerns turbulence and magnetic reconnection, two phenomena that disrupt the operation of nuclear fusion reactors.

    To Loureiro, MIT itself represents a fascinating system — one he’s been exploring since he joined the faculty in January 2016. “It’s great to be in an environment where the system will respond at the level you want,” he says. “Sometimes it’s hard to find an institution where there is a perfect resonance between what you want, the rhythm you want for your own research, and the institution itself. And MIT does this. MIT will basically respond to whatever you throw at it.”

    What drew Loureiro to plasma physics, he says, was energy. “If one is not naïve about today’s world and today’s society, one has to understand that there is an energy problem. And if you’re a physicist, you have the tools to try and do something about it.”

    Fusion reactors, with their potential to provide continuous, greenhouse gas emissions-free energy, are one answer to the problem. A working fusion reactor gleans its energy from the organized movement of plasma, a hot ionized gas, along tracks formed by magnetic bands within the reactor, similar to the way the solar plasma on the surface of the sun moves along paths dictated by the sun’s magnetic field. Loureiro, who specializes in plasma as it relates to both reactor physics and astrophysics, knows the details of this parallel well. Sometimes the magnetic field lines on the sun’s surface rearrange themselves, and the resulting “violent phenomenon” of energy release is a solar flare, Loureiro says.

    Something similar can take place within fusion reactors. A reactor’s plasma occasionally will spontaneously reconfigure the prescribed magnetic field, inducing instabilities that may abruptly terminate the experiment. In addition, fusion reactor plasmas tend to be in a turbulent state. Both effects hinder the reactor’s ability to operate.

    Loureiro uses theoretical calculations and supercomputer modeling to try to figure out what causes those phenomena and what can be done to avoid them in future experiments. He says, “When someone proposes a new concept for a fusion reactor, or when one is planning new experiments on existing machines, one of the things you have to think about is, how will the plasma in it behave?” His simulations use several theoretical approaches to tackle such questions. He notes that his simulations are not meant to be prescriptive, which would require a high level of complexity and realism. “My approach is at a more fundamental level,” he says. “I take very complex phenomena and try to understand them by reducing them to the simplest possible system that still captures the essential physics of those phenomena.”

    Loureiro looks forward to continuing to involve more students in his research. In his lab and in the classroom, he already works with both undergraduate and graduate physics students. He is currently teaching a numerical methods class for graduate students in nuclear science and engineering, and an undergraduate introductory seminar on plasma physics and fusion energy. “One of the things that has impressed me most about MIT is how talented the students are,” Loureiro says. “People told me, ‘Oh, the students are just amazing.’ But I don’t think I expected just how amazing they are.”

    He feels the same esteem for his fellow researchers. “It’s inspirational to be on the same campus as people in completely different areas from mine who are world leaders in their fields,” he says. “That’s something that is unique to MIT and that I find incredibly motivating.”

    He’s also inspired by the vibrant environment of the Plasma Science and Fusion Center (PSFC). “I feel that some of the most interesting ideas in fusion right now are being explored at the PSFC,” he says. “It’s great to be an active part of that excitement.”

    Hundreds of MIT faculty members collaborate with MITEI. To learn more about their work, visit MITEI’s research page.

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