Author: mantulin

Ibrahim Cissé, Ruth Lehmann, and Silvi Rouskin awarded 2021 Vilcek Prize

Prize recognizes contributions to biomedical research made by immigrant scientists.

Raleigh McElvery | Sandi Miller | Department of Biology | Department of Physics
September 25, 2020

Associate professor of physics and biology Ibrahim Cissé, professor of biology and Whitehead Institute Director Ruth Lehmann, and Andria and Paul Heafy Whitehead Fellow Silvi Rouskin have been awarded 2021 Vilcek Prizes. The Vilcek Foundation was established in 2000 by Jan and Marica Vilcek, who emigrated from the former Czechoslovakia. Their prizes honor the outstanding contributions of immigrants in the sciences and the arts. Prizewinners will be honored in an April ceremony.

“The 2021 awards celebrate the diversity of immigrant contributions to biomedical research, to filmmaking, and to society,” Vilcek Foundation President Rick Kinsel said in a press release. “In recognizing foreign-born scientists and dynamic leaders in the arts and in public service, we seek to expand the public dialogue about the intellectual value and artistic diversity that immigration provides the United States.”

Ibrahim Cissé

A faculty member in the departments of Physics and Biology, Ibrahim Cissé received the Vilcek Prize for Creative Promise in Biomedical Science for using super-resolution biological imaging to directly visualize the dynamic nature of gene expression in living cells.

Born in Niger, Cissé assumed he would be a lawyer like his father, but he soon became inspired by the science he saw in American films. His high school did not have a laboratory, so he completed high school two years early, enrolled in an English as a Second Language program at the University of North Carolina at Wilmington, and enrolled in Durham Technical Community College before transferring to North Carolina Central University, a historically Black college that was notable for its undergraduate science and mathematics research programs.

Following graduation, he spent a summer at Princeton University working in condensed matter physics. There, Cissé was confronted by physics professor Paul Chaikin with a question about elliptical geometry and particle density, using M&M’s candies. Cissé’s creative problem-solving enabled him and his fellow researchers to develop experiments for observing and quantifying their results, and they coauthored a paper that was published in Science magazine.

For graduate studies, he was at the University of Illinois at Urbana-Champaign, and earned a PhD under the supervision of single-molecule biophysicist Taekjip Ha, who was leading research in high-resolution, single-biomolecule imaging technology. Cissé’s interest in using physics to understand the physical processes in biology led him to a post-doctoral fellowship at École Normale Supérieure Paris. He showed that RNA polymerase II, a critical protein in gene expression, forms fleeting (“transient”) clusters with similar molecules in order to transcribe DNA into RNA. He joined the Howard Hughes Medical Institute’s Janelia Research Campus as a research specialist in the Transcription Imaging Consortium, before joining the MIT Department of Physics in 2014, and was recently granted tenure and a joint appointment in biology.

The Cissé Laboratory focuses on the development of high-resolution microscopy techniques to examine the behavior of single biomolecules in living cells, and his own research focuses on the process by which DNA gets decoded into RNA. His Time-Correlated Photoactivated Localization Microscopy (tcPALM) technique of imaging was able to peer inside living cells to study the dynamics of protein clusters. This discovery has led to breakthroughs in viewing the clustering and droplet-like behavior of RNA polymerase II during RNA transcription. In an interview with MIT News, he stated, “It’s becoming clearer that physics may be just as important as biology for understanding how cells work.”

Other national and international awards include the Young Fluorescence Investigator Award from the American Biophysical Society, the Pew Biomedical Scholars, and the National Institute of Health Director’s New Innovator Award. He is a Next Einstein Forum fellow and was listed in Science News’ Scientists to Watch.

Ruth Lehmann

Professor of biology and director of Whitehead Institute for Biomedical Research Ruth Lehmann received the Vilcek Prize in Biomedical Science. As a developmental and cell biologist, she investigates the biology of germ cells, which give rise to sperm and eggs.

The daughter of a teacher and an engineer, Lehmann was captivated by science from a young age. She grew up in Cologne, Germany, and majored in biology as an undergraduate at the University of Tübingen. Her Fulbright Fellowship in 1977 brought her to the University of Washington in Seattle, and served as the catalyst that spurred her career using fruit flies to understand germ cell biology. She went on to train with renowned fruit fly geneticists Gerold Schubiger and Jose Campos-Ortega, learning classical developmental biology and electron microscopy techniques. She then performed her doctoral research with future Nobel laureate Christiane Nüsslein-Volhard at the Max Planck Institute for Developmental Genetics. There, Lehmann probed the maternal genes that influence fruit fly embryo development — studies that ignited her fervor for germ cell research. Later, as a postdoc at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, she worked with Michael Wilcox and Peter Lawrence to pinpoint the molecules that control the fate of these vital cells.

Lehmann arrived at MIT in 1988, where she served as a professor and member of the Whitehead Institute for eight years. “Being an immigrant in the United States was exhilarating,” she says, “because of the openness to new ideas and the encouragement to take risks and be creative.”

She was recruited to the Skirball Institute at New York University (NYU), where she was appointed as the institute’s director, as well as the director of the Helen and Martin Kimmel Center for Stem Cell Biology, and chair of the Department of Cell Biology at NYU’s Langone Medical Center.

Lehmann returned to MIT this summer to launch the Lehmann Lab and become director of the Whitehead Institute in July.

Although she began her career focused on the formation and maintenance of germ cells, Lehmann has since revealed key insights into their migration — and more recently into mitochondrial inheritance. Her influential work regarding the development and behavior of these essential cells has also enriched related fields including stem cell biology, lipid biology, and DNA repair.

“It means so much to me to be recognized as an immigrant and a researcher,” says Lehmann. “In these days, immigrants don’t feel as welcomed as I did when I came to this country. For me, coming to the U.S. meant to be given a chance to live the dream of being a scientist. This allowed me to explore the fascinating biology of the germ line together with a group of incredibly talented trainees and staff, many of them immigrants themselves, and I share this wonderful recognition with them.”

Lehmann’s accolades include membership to the National Academy of Sciences, American Academy of Arts and Sciences, and European Molecular Biology Organization, as well as the Conklin Medal from the Society for Developmental Biology, the Porter Award from the American Society for Cell Biology, and the Lifetime Achievement Award from the German Society for Developmental Biology.

Silvi Rouskin

The Andria and Paul Heafy Whitehead Fellow at the Whitehead Institute, Silvi Rouskin received the Vilcek Prize for Creative Promise in Biomedical Science for developing methods to unravel the shapes of RNA molecules inside cells — aiding the potential development of RNA-based therapeutics.

The daughter of rock musicians in early-1980s communist Bulgaria, she grew up fascinated with the geometry of the flora and fauna around her. At 10, she started saving her lunch money to buy a miniature telescope. At 15 she knew that her best chances to study science would be in the United States, and so she joined a student exchange program in Idaho.

“I was not only allowed but encouraged to question my superiors,” she recalls. “I felt free to speak my mind, and often debated with my teachers.” Rouskin completed her GED and studied physics and biochemistry at the Florida Institute of Technology at 16.

As a staff research associate in the laboratory of Joseph DeRisi at the University of California at San Francisco, Rouskin first began studying RNA, using microarrays to detect and track viral infection. She opted to stay at UCSF to pursue her PhD in biochemistry and molecular biology.

She joined the Whitehead Institute in 2015, and established the Rouskin Lab to focus on the structure of RNA molecules, including viruses, and to determine how structure influences RNA processing and gene expression in HIV-1 and other viruses. Most recently, Rouskin uncovered the higher-order structure of the RNA genome of SARS-CoV2 — the virus that causes Covid-19  — in infected cells at high resolution.

“The goal of my own lab has been to perform basic RNA research with clear therapeutic applications and a particular focus on the vulnerabilities of RNA viruses,” says Rouskin. “I want my research to matter for medicine, and so I always approach my research with a cognizance of how my work can directly benefit people.”

Rouskin has also received the Harold M. Weintraub Graduate Student Award for outstanding achievements in biological sciences and the Burroughs Wellcome Fund Career Award at the Scientific Interface.

School of Science appoints 12 faculty members to named professorships
School of Science
September 11, 2020

The School of Science has awarded chaired appointments to 12 faculty members. These faculty, who are members of the departments of Biology; Brain and Cognitive Sciences; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics, receive additional support to pursue their research and develop their careers.

Kristin Bergmann, an assistant professor in the Department of Earth, Atmospheric and Planetary Sciences, has been named a D. Reid Weedon, Jr. ’41 Career Development Professor. This is a three-year professorship. Bergmann’s research integrates across sedimentology and stratigraphy, geochemistry, and geobiology to reveal aspects of Earth’s ancient environments. She aims to better constrain Earth’s climate record and carbon cycle during the evolution of early eukaryotes, including animals. Most of her efforts involve reconstructing the details of carbonate rocks, which store much of Earth’s carbon, and thus, are an important component of Earth’s climate system over long timescales.

Joseph Checkelscky is an associate professor in the Department of Physics and has been named a Mitsui Career Development Professor in Contemporary Technology, an appointment he will hold until 2023. His research in quantum materials relies on experimental methods at the intersection of physics, chemistry, and nanoscience. This work is aimed toward synthesizing new crystalline systems that manifest their quantum nature on a macroscopic scale. He aims to realize and study these crystalline systems, which can then serve as platforms for next-generation quantum sensors, quantum communication, and quantum computers.

Mircea Dincă, appointed a W. M. Keck Professor of Energy, is a professor in the Department of Chemistry. This appointment has a five-year term. The topic of Dincă’s research falls largely under the umbrella of energy storage and conversion. His interest in applied energy usage involves creating new organic and inorganic materials that can improve the efficiency of energy collection, storage, and generation while decreasing environmental impacts. Recently, he has developed materials for efficient air-conditioning units and been collaborating with Automobili Lamborghini on electric vehicle design.

Matthew Evans has been appointed to a five-year Mathworks Physics Professorship. Evans, a professor in the Department of Physics, focuses on the instruments used to detect gravitational waves. A member of MIT’s Laser Interferometer Gravitational-Wave Observatory (LIGO) research group, he engineers ways to fine-tune the detection capabilities of the massive ground-based facilities that are being used to identify collisions between black holes and stars in deep space. By removing thermal and quantum limitations, he can increase the sensitivity of the device’s measurements and, thus, its scope of exploration. Evans is also a member of the MIT Kavli Institute for Astrophysics and Space Research.

Evelina Fedorenko is an associate professor in the Department of Brain and Cognitive Sciences and has been named a Frederick A. (1971) and Carole J. Middleton Career Development Professor of Neuroscience. Studying how the brain processes language, Fedorenko uses behavioral studies, brain imaging, neurosurgical recording and stimulation, and computational modelling to better grasp language comprehension and production. In her efforts to elucidate how and what parts of the brain support language processing, she evaluates both typical and atypical brains. Fedorenko is an associate member of the McGovern Institute for Brain Research.

Ankur Jain is an assistant professor in the Department of Biology and now a Thomas D. and Virginia W. Cabot Career Development Professor. He will hold this career development appointment for a term of three years. Jain studies how cells organize their contents. Within a cell, there are numerous compartments that form due to weak interactions between biomolecules and exist without an enclosing membrane. By analyzing the biochemistry and biophysics of these compartments, Jain deduces the principles of cellular organization and its dysfunction in human disease. Jain is also a member of the Whitehead Institute for Biomedical Research.

Pulin Li, an assistant professor in the Department of Biology and the Eugene Bell Career Development Professor of Tissue Engineering for the next three years, explores genetic circuitry in building and maintain a tissue. In particular, she investigates how communication circuitry between individual cells can extrapolate into multicellular behavior using both natural and synthetically generated tissues, for which she combines the fields of synthetic and systems biology, biophysics, and bioengineering. A stronger understanding of genetic circuitry could allow for progress in medicine involving embryonic development and tissue engineering. Li is a member of the Whitehead Institute for Biomedical Research.

Elizabeth Nolan, appointed an Ivan R. Cottrell Professor of Immunology, investigates innate immunity and infectious disease. The Department of Chemistry professor, who will hold this chaired professorship for five years, combines experimental chemistry and microbiology to learn about human immune responses to, and interactions with, microbial pathogens. This research includes elucidating the fight between host and pathogen for essential metal nutrients and the functions of host-defense peptides and proteins during infection. With this knowledge, Nolan contributes to fundamental understanding of the host’s ability to combat microbial infection, which may provide new strategies to treat infectious disease.

Leigh “Wiki” Royden is now a Cecil and Ida Green Professor of Geology and Geophysics. The five-year appointment supports her research on the large-scale dynamics and tectonics of the Earth as a professor in the Department of Earth, Atmospheric and Planetary Sciences. Fundamental to geoscience, the tectonics of regional and global systems are closely linked, particularly through the subduction of the plates into the mantle. Royden’s research adds to our understanding a of the structure and dynamics of the crust and the upper portion of the mantle through observation, theory and modeling. This progress has profound implications for global natural events, like mountain building and continental break-up.

Phiala Shanahan has been appointed a Class of 1957 Career Development Professor for three years. Shanahan is an assistant professor in the Department of Physics, where she specializes in theoretical and nuclear physics. Shanahan’s research uses supercomputers to provide insight into the structure of protons and nuclei in terms of their quark and gluon constituents. Her work also informs searches for new physics beyond the current Standard Model, such dark matter. She is a member of the MIT Center for Theoretical Physics.

Xiao Wang, an assistant professor, has also been named a new Thomas D. and Virginia W. Cabot Professor. In the Department of Chemistry, Wang designs and produces novel methods and tools for analyzing the brain. Integrating chemistry, biophysics, and genomics, her work provides higher-resolution imaging and sampling to explain how the brain functions across molecular to system-wide scales. Wang is also a core member of the Broad Institute of MIT and Harvard.

Bin Zhang has been appointed a Pfizer Inc-Gerald Laubach Career Development Professor for a three-year term. Zhang, an assistant professor in the Department of Chemistry, hopes to connect the framework of the human genome sequence with its various functions on various time and spatial scales. By developing theoretical and computational approaches to categorize information about dynamics, organization, and complexity of the genome, he aims to build a quantitative, predictive modelling tool. This tool could even produce 3D representations of details happening at a microscopic level within the body.

Covid-19 scientific leaders share expertise in new MIT class
Greta Friar | Whitehead Institute
September 9, 2020

As the Covid-19 pandemic swept across the globe, bringing everyday life to a screeching halt, researchers at MIT and its affiliates ramped down much of their lab work and stopped teaching classes in person, but refused to come to a standstill. Instead, they changed tacks and took action investigating the many unknowns of Covid-19 and the virus that causes it (SARS-CoV-2), organizing pandemic responses, and communicating with the public and each other about what they knew.

One result of this period was the advent of a new course, aimed at providing MIT students with information on the science of the pandemic. The MIT Department of Biology tapped two scientists with experience working on pandemics to spearhead a course, 7.00 (COVID-19, SARS-CoV-2 and the Pandemic), which began Sept. 1. Whitehead Institute member and MIT Professor Richard Young, who had been quick to organize Covid-19 related research efforts, and Ragon Institute Associate Director Facundo Batista, a resident expert on immunology and infectious disease, agreed to lead the course.

The class meets virtually on Tuesday mornings, and a public livestream and recordings are available for anyone who wants to watch the lectures. Students who are taking the course for credit also gain access to a weekly session led by Lena Afeyan, a teaching assistant and MIT graduate student in Young’s lab at the Whitehead Institute. The session provides relevant background information on the science before the lectures.

Getting students up to speed on what is and is not known about the pandemic is no easy task. The science is complex and, in these early days, full of unknowns. Experts in many fields must pool their knowledge; virologists, immunologists, epidemiologists, public health researchers, clinicians, and more are focused on important pieces of the puzzle. Therefore, Young and Batista reached out to the leaders in all of those fields to give lectures in the course. Students will hear from experts that include Anthony Fauci, the longtime director of the National Institute of Allergy and Infectious Diseases, as well as David Baltimore of Caltech; Kizzmekia Corbett of the National Institutes of Health; Britt Glaunsinger of the University of California at Berkeley; Akiko Iwasaki of Yale University; Eric Lander of the Broad Institute of MIT and Harvard; Michel Nussenzweig of Rockefeller University; Arlene Sharpe of Harvard Medical School and Brigham and Women’s Hospital; Bruce Walker of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard; and others at the forefront of Covid-19 efforts. The course faculty agree that the best way to get accurate information to students is to have the experts provide it directly.

Designing the course

For many of the students, Covid-19 may be their first serious encounter with a pandemic, but a number of the lecturers have worked on the AIDS pandemic or other widespread infectious diseases, which they draw on when teaching.

“I like to put the coronavirus in the context of viruses I know better, like flu and HIV and polio virus,” says David Baltimore, the Nobel laureate professor of biology and president emeritus at Caltech who was previously the first director of the Whitehead Institute and a professor at MIT. However, the scientists’ relevant backgrounds can only help so much. The new coronavirus is a unique and difficult research subject.

“It has no obvious evolutionary relationship to other viruses. It’s got a much longer RNA, many more genes, so more complexity of function, more complexity of genetics, and it’s received relatively little study up until recently,” Baltimore says. “There is a lot more work that needs to be done.”

When planning the class, Young wanted to give all of the information needed to understand what is likely the first pandemic to powerfully impact the lives of the undergraduates taking the course. His motives were pedagogical — and practical.

“If we give people knowledge of what’s known and not known about the virus, provided by experts whom they trust, they can help us come up with solutions,” Young says.

Young and Batista expect that some of their students will soon be conducting their own Covid-19 research. Batista hopes that this experience will encourage students to think even beyond the scope of the current pandemic.

“I think the U.S. and the Western world have underestimated the risk of infectious diseases because the big pandemics have been happening elsewhere. This class is about bringing people together on Covid-19, and more than that, [it is about] creating a consciousness about the threat of future infections,” Batista says.

Where to start?

The first lecture was given by Bruce Walker, director of the Ragon Institute. Walker provided an overview of the available information, including how the pandemic appears to have started, how the virus causes disease, and what the prospects are for treatment and vaccines. The level of the science is aimed at MIT undergraduates, but because the livestream audience may have different science backgrounds, Walker made sure to define basic terms and concepts as he went. The lecture was attended by 250 students, with more than 7,000 people watching the livestream.

Registered students can ask questions during a Q&A at the end of each lecture. Walker addressed students’ concerns about the U.S. response to the pandemic, the risk of reinfection, mutability of the virus, and challenges with new types of vaccines. With the aim of providing accurate information, his answers were not always reassuring. However, in spite of the many uncertainties that the scientists are grappling with, the course faculty’s message for students is an optimistic one.

“People have felt powerless in this pandemic,” Afeyan says. “A course like this can help people feel like they have the tools to do something about it. There is a plethora of problems that will stem from the pandemic, so there are lots of ways to get involved regardless of your field.”

Researchers have banded together across MIT, Whitehead Institute, Ragon Institute, and around the globe to address the pandemic. For students who want to join the research effort, the content of the lectures is paired with discussions during Afeyan’s sessions with researchers earlier in their careers, who can talk to the students about next steps should they choose to pursue one of the fields presented in the course.

As for students and audience members simply looking to understand the public health event that has so strongly impacted their world, the faculty hope that the course will provide them with the answers they need. Scientists are not the only ones dealing with lots of uncertainty these days, and there is value in learning what the experts know as they know it, straight from the source.

School of Science grows by 10
School of Science
September 9, 2020

Despite the upheaval caused by the coronavirus pandemic, 10 new faculty members have joined MIT in the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; Mathematics; and Physics. The School of Science welcomes these new faculty, most of whom began their appointment July 1, amidst efforts to update education and research plans for the fall semester. They bring exciting and valuable new areas of strength and expertise to the Institute.

Camilla Cattania is an earthquake scientist. She uses continuum mechanics, numerical simulations, and statistics to study fault mechanics and earthquake physics at different scales, from small repeating events to fault interaction on regional and global scales. The models she has developed can help forecast earthquake sequences caused by seismic or aseismic events, such as aftershocks and swarms induced by forcing mechanisms like magma moving under the Earth’s surface. She has also developed theoretical models to explain why certain faults rupture in predictable patterns while others do not. Cattania’s research plans include widening her focus to other tectonic settings and geometrically complex fault structures.

Cattania earned her bachelor’s and master’s degrees from Cambridge University in experimental and theoretical physics in 2011, after which she completed a PhD in Germany at the GFZ German Research Center for Geosciences and the University of Potsdam in 2015. Subsequently, she spent a few months as a researcher at Woods Hole Oceanographic Institution and as a postdoc at Stanford University and her doctoral institution. She joins the Department of Earth, Atmospheric and Planetary Sciences as an assistant professor.

Richard Fletcher researches quantum physics using atomic vapors one-millionth the density of air and one-millionth the temperature of deep space. By manipulating the gas with intricately sculpted laser beams and magnetic fields, he can engineer custom-made quantum worlds, which provide both a powerful test bed for theory and a wonderful playground for discovering new phenomena. The goal is to understand how interesting collective behaviors emerge from the underlying microscopic complexity of many interacting particles. Fletcher’s interests include superfluidity in two-dimensional gases, methods to probe the correlations between individual atoms, and how the interplay of interactions and magnetic fields leads to novel physics.

Fletcher is a graduate of Cambridge University, where he completed his bachelor’s in 2010. Before returning to Cambridge University to earn his PhD in 2015, he was a research fellow at Harvard University. He originally came to MIT as a postdoc in 2016 and now joins the Department of Physics as an assistant professor. Fletcher is a member of the MIT-Harvard Center for Ultracold Atoms.

William Frank investigates deformation of the Earth’s crust. He combines seismology and geodesy to explore the physical mechanisms that control the broad continuum of rupture modes and fault instabilities within the Earth. His research has illuminated the cascading rupture dynamics of slow fault slip and how the aftershocks that follow a large earthquake can reveal the underlying behavior of the host fault. Frank considers shallow shifts that cause earthquakes down to deep creep that is all-but-invisible at the surface. His insights work to improve estimates of seismic hazards induced by tectonic dynamics, volcanic processes, and human activity, which can then inform risk prediction and mitigation.

Frank holds a bachelor’s degree from the University of Michigan in earth systems science, which he received in 2009. The Institut de Physique du Globe de Paris awarded him a master’s degree in geophysics in 2011 and a PhD in 2014. He first joined MIT as a postdoc in 2015 before moving to the University of Southern California as an assistant professor in 2018. He now returns as an assistant professor in the Department of Earth, Atmospheric and Planetary Sciences.

Ronald Fernando Garcia Ruiz advances research on fundamental physics and nuclear structure largely through the development of novel laser spectroscopy techniques. He investigates the properties of subatomic particles using atoms and molecules made up of short-lived radioactive nuclei. Garcia Ruiz’s experimental work provides unique information about the fundamental forces of nature and offers new opportunities in the search beyond the Standard Model of particle physics. His previous research at CERN focused on the study of the emergence of nuclear phenomena and the properties of nuclear matter at the limits of existence.

Garcia Ruiz’s bachelor’s degree in physics was achieved in 2009 at Universidad Nacional de Colombia. After earning a master’s in physics in 2011 at Universidad Nacional Autónoma de México, he completed a doctoral degree in radiation and nuclear physics at KU Leuven in 2015. Prior to joining MIT, he was first a research associate at the University of Manchester from 2016-17 and then a research fellow at CERN. Garcia Ruiz has now joined the Department of Physics as an assistant professor. He began his appointment Jan. 1. He is also affiliated with the Laboratory for Nuclear Science.

Ruth Lehmann studies germ cells. The only cells in the body capable of producing an entire organism on their own, germ cells pass genomic information from one generation to the next via egg cells. By analyzing the organization of their informational material as well as the mechanics they regulate, such as the production of eggs and sperm, Lehmann hopes to expose germ cells’ unique ability to enable procreation. Her work in cellular and developmental biology is renowned for identifying how germ cells migrate and lead to the continuation of life. An advocate for fundamental research in science, Lehmann studies fruit flies as a model to unveil vital aspects of early embryonic development that have important implications for stem cell research, lipid biology, and DNA repair.

Lehmann earned her bachelor’s degree in biology from the University of Tubingen in Germany. She took an interlude from her education to carry out research at the University of Washington in the United States before returning to Germany. There, she earned a master’s equivalent from the University of Freiburg and a PhD from the University of Tubingen. Lehmann was subsequently a postdoc at the Medical Research Council Laboratory of Molecular Biology in the UK, after which she joined MIT. A faculty member and Whitehead Institute for Biomedical Research member from 1988 to 1996, she now returns after 23 years at New York University. Lehmann joins as a full professor in the Department of Biology and is the new director of the Whitehead Institute for Biomedical Research.

As an astrochemist, Brett McGuire is interested in the chemical origins of life and its evolution. He combines physical chemistry experiments and analyses with molecular spectroscopy in a lab, the results of which he then compares against astrophysics observation. His work ties together questions about the formation of planets and a planet’s ability to host and create life. McGuire does this by investigating the generation, presence, and fate of new molecules in space, which is vast and mostly empty, providing unique physical challenges on top of chemical specifications that can impact molecular formation. He has discovered several complex molecules already, including benzonitrile, a marker of carbon-based reactions occurring in an interstellar medium.

McGuire’s BS degree was awarded by the University of Illinois at Urbana-Champaign in 2009. He completed a master’s in physical chemistry in 2011 at Emory University and a PhD in 2015 at Caltech. He then pursued a postdoc at the National Radio Astronomy Observatory and the Harvard-Smithsonian Center for Astrophysics. He joins the Department of Chemistry as an assistant professor.

Dor Minzer works in the fields of mathematics and theoretical computer science. His interests revolve around computational complexity theory, or — more explicitly — probabilistically checkable proofs, Boolean function analysis, and combinatorics. With collaborators, he has proved the 2-to-2 Games Conjecture, a central problem in complexity theory closely related to the Unique-Games Conjecture. This work significantly advances our understanding of approximation problems and, in particular, our ability to draw the border between computationally feasible and infeasible approximation problems.

Minzer is not new to online education. After earning his bachelor’s degree in mathematics in 2014 and a PhD in 2018, both from Tel-Aviv University, he became a postdoc at the Institute for Advanced Study at Princeton University. He joins the Department of Mathematics as an assistant professor.

Lisa Piccirillo is a mathematician specializing in the study of three- and four-dimensional spaces. Her work in four-manifold topology has surprising applications to the study of mathematical knots. Perhaps most notably, Piccirillo proved that the Conway knot is not “slice.” For all other small knots, “sliceness” is readily determined, but this particular knot had remained a mystery since John Conway presented it in the mid-1900s. After hearing about the problem at a conference, Piccirillo took only a week to formulate a proof. She is broadly interested in low-dimensional topology and knot theory, and employs constructive techniques in four-manifolds.

Piccirillo earned her BS in mathematics in 2013 from Boston College. Her PhD in mathematics was earned from the University of Texas at Austin in 2019, and from 2019-20 she was a postdoc at Brandeis University. She joins the Department of Mathematics as an assistant professor.

Jonathan Weissman’s research interest is protein folding and structure, an integral function of life. His purview encompasses the expression of human genes and the lineage of cells, as well as protein misfolding, which can cause diseases and other physiological issues. He has made discoveries surrounding protein folding mechanisms, the development of CRISPR gene-editing tools, and other new therapeutics and drugs, and in the process generated innovative experimental and analytical methods and technologies. One of his novel methods is the ribosome profiling approach, which allows researchers to observe in vivo molecular translation, the process by which a protein is created according to code provided by RNA, a major advancement for health care.

Weissman earned a bachelor’s degree in physics from Harvard University in 1998 and a PhD from MIT in 1993. After completing his doctoral degree, he left MIT to become a postdoc at Yale University for three years, and then a faculty member at the University of California at San Francisco in 1996. He returns to MIT to join the Department of Biology as a full professor and a member of the Whitehead Institute for Biomedical Research. He is also a Howard Hughes Medical Institute investigator.

Yukiko Yamashita, a stem cell biologist, delves into the origins of multicellular organisms, asking questions about how genetic information is passed from one generation to the next, essentially in perpetuity, via germ cells (eggs and sperm), and how a single cell (fertilized egg) becomes an organism containing many different types of cells. The results of her work on stem cell division and gene transmission has implications for medicine and long-term human health. Using fruit flies as a model in the lab, she has revealed new areas of knowledge. For example, Yamashita has identified the mechanisms that enable a stem cell to produce two daughter cells with distinct fates, one a stem cell and one a differentiating cell, as well as the functions of satellite DNA, which she found to be crucial, unlike the “waste” they were previously thought to be.

Yamashita received her bachelor’s degree in biology in 1994 and her PhD in biophysics in 1999, both from Kyoto University. After being a postdoc at Stanford University for five years, she was appointed a faculty member at the University of Michigan in 2007. She joined the Department of Biology as a full professor with a July 1 start. She also became a member of the Whitehead Institute of Biomedical Research and is a standing investigator at the Howard Hughes Medical Institute.

SMART research enhances dengue vaccination in mice
Singapore-MIT Alliance for Research and Technology
August 13, 2020

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have found a practical way to induce a strong and broad immunity to the dengue virus based on proof-of-concept studies in mice. Dengue is a mosquito-borne viral disease with an estimated 100 million symptomatic infections every year. It is endemic in over 100 countries in the world, from the United States to Africa and wide swathes of Asia. In Singapore, over 1,700 dengue new cases were reported recently.

The study is reported in a paper titled “Sequential immunization induces strong and broad immunity against all four dengue virus serotypes,” published in NPJ Vaccines. It is jointly published by SMART researchers Jue Hou, Shubham Shrivastava, Hooi Linn Loo, Lan Hiong Wong, Eng Eong Ooi, and Jianzhu Chen from SMART’s Infectious Diseases and Antimicrobial Resistance (AMR) interdisciplinary research groups (IRGs).

The dengue virus (DENV) consists of four antigenically distinct serotypes and there is no lasting immunity following infection with any of the DENV serotypes, meaning someone can be infected again by any of the remaining three variants of DENVs.

Today, Dengvaxia is the only vaccine available to combat dengue. It consists of four variant dengue antigens, one for each of the four serotypes of dengue, expressed from attenuated yellow-fever virus. The current three doses of immunization with the tetravalent vaccine induce only suboptimal protection against DENV1 and DENV2. Furthermore, in people who have not been infected by dengue, the vaccine induces a more severe dengue infection in the future. Therefore, in most of the world, the vaccination is only given to those who have been previously infected.

To help overcome these issues, SMART researchers tested on mice whether sequential immunization (or one serotype per dose) induces stronger and broader immunity against four DENV serotypes than tetravalent-formulated immunization — and found that sequential immunization induced significantly higher levels of virus-specific T cell responses than tetravalent immunization. Moreover, sequential immunization induced higher levels of neutralizing antibodies to all four DENV serotypes than tetravalent vaccination.

“The principle of sequential immunization generally aligns with the reality for individuals living in dengue-endemic areas, whose immune responses may become protective after multiple heterotypic exposures,” says Professor Eng Eong Ooi, SMART AMR principal investigator and senior author of the study. “We were able to find a similar effect based on the use of sequential immunization, which will pave the way for a safe and effective use of the vaccine and to combat the virus.”

Upon these promising results, the investigators will aim to test the sequential immunization in humans in the near future.

The work was supported by the National Research Foundation (NRF) Singapore through the SMART Infectious Disease Research Program and AMR IRG. SMART was established by MIT in partnership with the NRF Singapore in 2007. SMART is the first entity in the Campus for Research Excellence and Technological Enterprise (CREATE) developed by NRF.  SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, performing cutting-edge research of interest to both Singapore and MIT. SMART currently comprises an Innovation Centre and five IRGs: AMR, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems. SMART research is funded by the NRF Singapore under the CREATE program.

The AMR IRG is a translational research and entrepreneurship program that tackles the growing threat of antimicrobial resistance. By leveraging talent and convergent technologies across Singapore and MIT, they aim to tackle AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, they provide transformative, holistic solutions for Singapore and the world.

3 Questions: Jonathan King on the future of nuclear weapons testing

Professor of biology discusses a scientist’s responsibility to speak out about important issues that affect our nation and the world.

Raleigh McElvery | Department of Biology
July 29, 2020

In an open letter published on July 16 in Science, four MIT professors and nearly 70 additional scientific leaders called upon fellow researchers to urge U.S. government officials to halt plans to restart nuclear weapons testing. Corresponding author and professor of biology Jonathan King sat down to discuss the history of nuclear testing, his personal ties to the issue, and his responsibilities as a scientist. He also co-chairs the Nuclear Disarmament Working Group of Massachusetts Peace Action, MIT’s annual Reducing the Threat of Nuclear War conference, and the editorial board of the MIT Faculty Newsletter.

Q: What events have made you passionate about the issue of nuclear weapons testing?

A: I grew up in the shadow of nuclear war, participating in drills at school where you would duck under your desk. During the Cold War, the world’s nations exploded hundreds of dangerous nuclear tests, releasing radioactivity into the atmosphere in order to develop these weapons. I was a college student during the Cuban Missile Crisis, and remember vividly the fear of a nuclear exchange.

Around that time, it became clear to our nation’s leaders that this was not the way to go. In his famous speech at American University, President Kennedy reversed direction. Professor of chemistry at Caltech Linus Pauling led an effort with his wife to back Kennedy and collect 9,000 signatures from scientists endorsing the president’s Partial Nuclear Test Ban Treaty. This was before the internet, so getting 9,000 signatures was not easy, and it had a national impact. I was actually a graduate student at Caltech, following up on Pauling’s work on proteins, when the treaty was ratified and he was awarded the Nobel peace prize for his work.

When I arrived at MIT as an assistant professor, Jerome Wiesner was the Institute president. He was also a key player in pushing the Partial Nuclear Test Ban Treaty, and Kennedy had previously named him chair of the President’s Science Advisory Committee (PSAC). MIT was full of world leaders in nuclear disarmament, including physicists who had worked on the bomb and decided it was a mistake. I’m not a physicist, but I was among the generation at MIT that was very vocal about these issues.

Q: What is the current state of nuclear weapon testing and regulation in the United States, and what concerns do you have about renewed testing?

A: The U.S. hasn’t tested a nuclear weapon since 1992. In that period of time, the Comprehensive Test Ban Treaty (CTBT) was developed by many nations, agreeing not to conduct a nuclear weapons test of any yield. The Senate hasn’t ratified it, but in 2016 the U.S. did adopt UN Security Council Resolution 2310, agreeing to uphold the goal of the CTBT and withhold nuclear testing.

However, the current administration is proposing to modernize nuclear weapons and restart testing, which is both provocative and dangerous. Even if these tests are small, contained, and underground, they will still open the door for other nations to restart testing of their own, and possibly lead to a new nuclear weapons arms race.

When a nuclear weapon — either a conventional bomb or hydrogen bomb — explodes, many radioactive isotopes are produced. Some of them are short-lived and decay quickly, but others like strontium-90 are much longer-lived. These ones can make you sick very slowly, and some can mutate or damage DNA. Even underground tests can leak radioactivity into the atmosphere and environment.

Q: What spurred you and your colleagues to write an open letter to Science, and what was your goal in doing so?

A: Our letter was signed by 70 scientific leaders and Nobel Prize winners, and calls upon the scientific community to warn the nation that this is a dangerous way to go. We also urged the Senate to ratify the CTBT, and pass a new bill introduced by Senator Ed Markey called the Preserving Leadership Against Nuclear Explosives Testing (PLANET) Act — which would prevent spending money on the renewal of testing.

I come from a culture that views scientists as public servants. All my research has been funded by taxpayer dollars, and with that comes a responsibility to help address threats to the community. The very history of my department, the MIT Department of Biology, is tied to scientists taking a stand against social and political issues. I was just a young assistant professor when faculty members like David Baltimore and Ethan Signer led demonstrations to oppose the Vietnam War. It was a very open environment and we supported one another.

These days, science is simply a career. You do your work and you keep your eyes to the bench. But the world can be a better place if we take our eyes off the bench occasionally. So this letter is a reminder to our colleagues: Get involved, and consider it our contribution to the general public who support our research.

Bringing RNA into genomics

ENCODE consortium identifies RNA sequences that are involved in regulating gene expression.

Anne Trafton | MIT News Office
July 29, 2020

The human genome contains about 20,000 protein-coding genes, but the coding parts of our genes account for only about 2 percent of the entire genome. For the past two decades, scientists have been trying to find out what the other 98 percent is doing.

A research consortium known as ENCODE (Encyclopedia of DNA Elements) has made significant progress toward that goal, identifying many genome locations that bind to regulatory proteins, helping to control which genes get turned on or off. In a new study that is also part of ENCODE, researchers have now identified many additional sites that code for RNA molecules that are likely to influence gene expression.

These RNA sequences do not get translated into proteins, but act in a variety of ways to control how much protein is made from protein-coding genes. The research team, which includes scientists from MIT and several other institutions, made use of RNA-binding proteins to help them locate and assign possible functions to tens of thousands of sequences of the genome.

“This is the first large-scale functional genomic analysis of RNA-binding proteins with multiple different techniques,” says Christopher Burge, an MIT professor of biology. “With the technologies for studying RNA-binding proteins now approaching the level of those that have been available for studying DNA-binding proteins, we hope to bring RNA function more fully into the genomic world.”

Burge is one of the senior authors of the study, along with Xiang-Dong Fu and Gene Yeo of the University of California at San Diego, Eric Lecuyer of the University of Montreal, and Brenton Graveley of UConn Health.

The lead authors of the study, which appears today in Nature, are Peter Freese, a recent MIT PhD recipient in Computational and Systems Biology; Eric Van Nostrand, Gabriel Pratt, and Rui Xiao of UCSD; Xiaofeng Wang of the University of Montreal; and Xintao Wei of UConn Health.

RNA regulation

Much of the ENCODE project has thus far relied on detecting regulatory sequences of DNA using a technique called ChIP-seq. This technique allows researchers to identify DNA sites that are bound to DNA-binding proteins such as transcription factors, helping to determine the functions of those DNA sequences.

However, Burge points out, this technique won’t detect genomic elements that must be copied into RNA before getting involved in gene regulation. Instead, the RNA team relied on a technique known as eCLIP, which uses ultraviolet light to cross-link RNA molecules with RNA-binding proteins (RBPs) inside cells. Researchers then isolate specific RBPs using antibodies and sequence the RNAs they were bound to.

RBPs have many different functions — some are splicing factors, which help to cut out sections of protein-coding messenger RNA, while others terminate transcription, enhance protein translation, break down RNA after translation, or guide RNA to a specific location in the cell. Determining the RNA sequences that are bound to RBPs can help to reveal information about the function of those RNA molecules.

“RBP binding sites are candidate functional elements in the transcriptome,” Burge says. “However, not all sites of binding have a function, so then you need to complement that with other types of assays to assess function.”

The researchers performed eCLIP on about 150 RBPs and integrated those results with data from another set of experiments in which they knocked down the expression of about 260 RBPs, one at a time, in human cells. They then measured the effects of this knockdown on the RNA molecules that interact with the protein.

Using a technique developed by Burge’s lab, the researchers were also able to narrow down more precisely where the RBPs bind to RNA. This technique, known as RNA Bind-N-Seq, reveals very short sequences, sometimes containing structural motifs such as bulges or hairpins, that RBPs bind to.

Overall, the researchers were able to study about 350 of the 1,500 known human RBPs, using one or more of these techniques per protein. RNA splicing factors often have different activity depending on where they bind in a transcript, for example activating splicing when they bind at one end of an intron and repressing it when they bind the other end. Combining the data from these techniques allowed the researchers to produce an “atlas” of maps describing how each RBP’s activity depends on its binding location.

“Why they activate in one location and repress when they bind to another location is a longstanding puzzle,” Burge says. “But having this set of maps may help researchers to figure out what protein features are associated with each pattern of activity.”

Additionally, Lecuyer’s group at the University of Montreal used green fluorescent protein to tag more than 300 RBPs and pinpoint their locations within cells, such as the nucleus, the cytoplasm, or the mitochondria. This location information can also help scientists to learn more about the functions of each RBP and the RNA it binds to.

“The strength of this manuscript is in the generation of a comprehensive and multilayered dataset that can be used by the biomedical community to develop therapies targeted to specific sites on the genome using genome-editing strategies, or on the transcriptome using antisense oligonucleotides or agents that mediate RNA interference,” says Gil Ast, a professor of human molecular genetics and biochemistry at Tel Aviv University, who was not involved in the research.

Linking RNA and disease

Many research labs around the world are now using these data in an effort to uncover links between some of the RNA sequences identified and human diseases. For many diseases, researchers have identified genetic variants called single nucleotide polymorphisms (SNPs) that are more common in people with a particular disease.

“If those occur in a protein-coding region, you can predict the effects on protein structure and function, which is done all the time. But if they occur in a noncoding region, it’s harder to figure out what they may be doing,” Burge says. “If they hit a noncoding region that we identified as binding to an RBP, and disrupt the RBP’s motif, then we could predict that the SNP may alter the splicing or stability of the gene.”

Burge and his colleagues now plan to use their RNA-based techniques to generate data on additional RNA-binding proteins.

“This work provides a resource that the human genetics community can use to help identify genetic variants that function at the RNA level,” he says.

The research was funded by the National Human Genome Research Institute ENCODE Project, as well as a grant from the Fonds de Recherche de Québec-Santé.

Gene-controlling mechanisms play key role in cancer progression

Study finds “epigenomic” alterations evolve as lung tumors become more aggressive and metastasize.

Anne Trafton | MIT News Office
July 22, 2020

As cancer cells evolve, many of their genes become overactive while others are turned down. These genetic changes can help tumors grow out of control and become more aggressive, adapt to changing conditions, and eventually lead the tumor to metastasize and spread elsewhere in the body.

MIT and Harvard University researchers have now mapped out an additional layer of control that guides this evolution — an array of structural changes to “chromatin,” the mix of proteins, DNA, and RNA that makes up cells’ chromosomes. In a study of mouse lung tumors, the researchers identified 11 chromatin states, also called epigenomic states, that cancer cells can pass through as they become more aggressive.

“This work provides one of the first examples of using single-cell epigenomic data to comprehensively characterize genes that regulate tumor evolution in cancer,” says Lindsay LaFave, an MIT postdoc and the lead author of the study.

In addition, the researchers showed that a key molecule they found in the more aggressive tumor cell states is also linked to more advanced forms of lung cancer in humans, and could be used as a biomarker to predict patient outcomes.

Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research, and Jason Buenrostro, an assistant professor of stem cell and regenerative biology at Harvard University, are the senior authors of the study, which appears today in Cancer Cell.

Epigenomic control

While a cell’s genome contains all of its genetic material, the epigenome plays a critical role in determining which of these genes will be expressed. Every cell’s genome has epigenomic modifications — proteins and chemical compounds that attach to DNA but do not alter its sequence. These modifications, which vary by cell type, influence the accessibility of genes and help to make a lung cell different from a neuron, for example.

Epigenomic changes are also believed to influence cancer progression. In this study, the MIT/Harvard team set out to analyze the epigenomic changes that occur as lung tumors develop in mice. They studied a mouse model of lung adenocarcinoma, which results from two specific genetic mutations and closely recapitulates the development of human lung tumors.

Using a new technology for single-cell epigenome analysis that Buenrostro had previously developed, the researchers analyzed the epigenomic changes that occur as tumor cells evolve from early stages to later, more aggressive stages. They also examined tumor cells that had metastasized beyond the lungs.

This analysis revealed 11 different chromatin states, based on the locations of epigenomic alterations and density of the chromatin. Within a single tumor, there could be cells from all 11 of the states, suggesting that cancer cells can follow different evolutionary pathways.

For each state, the researchers also identified corresponding changes in where gene regulators called transcription factors bind to chromosomes. When transcription factors bind to the promoter region of a gene, they initiate the copying of that gene into messenger RNA, essentially controlling which genes are active. Chromatin modifications can make gene promoters more or less accessible to transcription factors.

“If the chromatin is open, a transcription factor can bind and activate a specific gene program,” LaFave says. “We were trying to understand those transcription factor networks and then what their downstream targets were.”

As the structure of tumor cells’ chromatin changed, transcription factors tended to target genes that would help the cells to lose their original identity as lung cells and become less differentiated. Eventually many of the cells also gained the ability to leave their original locations and seed new tumors.

Much of this process was controlled by a transcription factor called RUNX2. In more aggressive cancer cells, RUNX2 promotes the transcription of genes for proteins that are secreted by cells. These proteins help remodel the environment surrounding the tumor to make it easier for cancer cells to escape.

The researchers also found that these aggressive, premetastatic tumor cells were very similar to tumor cells that had already metastasized.

“That suggests that when these cells were in the primary tumor, they actually changed their chromatin state to look like a metastatic cell before they migrated out into the environment,” LaFave says. “We believe they undergo an epigenetic change in the primary tumor that allows them to become migratory and then seed in a distal location like the lymph nodes or the liver.”

A new biomarker

The researchers also compared the chromatin states they identified in mouse tumor cells to chromatin states seen in human lung tumors. They found that RUNX2 was also elevated in more aggressive human tumors, suggesting that it could serve as a biomarker for predicting patient outcomes.

“The RUNX positive state was very highly predictive of poor survival in human lung cancer patients,” LaFave says. “We’ve also shown the inverse, where we have signatures of early states, and they predict better prognosis for patients. This suggests that you can use these single-cell gene regulatory networks as predictive modules in patients.”

RUNX could also be a potential drug target, although it traditionally has been difficult to design drugs that target transcription factors because they usually lack well-defined structures that could act as drug docking sites. The researchers are also seeking other potential targets among the epigenomic changes that they identified in more aggressive tumor cell states. These targets could include proteins known as chromatin regulators, which are responsible for controlling the chemical modifications of chromatin.

“Chromatin regulators are more easily targeted because they tend to be enzymes,” LaFave says. “We’re using this framework to try to understand what are the important targets that are driving these state transitions, and then which ones are therapeutically targetable.”

The research was funded by a Damon Runyon Cancer Foundation postdoctoral fellowship, the Paul G. Allen Frontiers Group, the National Institutes of Health, and the Koch Institute Support (core) Grant from the National Cancer Institute.

3 Questions: Ibrahim Cissé on using physics to decipher biology

A biophysicist employs super-resolution microscopy to peer inside living cells and witness never-before-seen phenomena.

Raleigh McElvery | Department of Biology
July 23, 2020

How do cells use physics to carry out biological processes? Biophysicist Ibrahim Cissé explores this fundamental question in his interdisciplinary laboratory, leveraging super-resolution microscopy to probe the properties of living matter. As a postdoc in 2013, he discovered that RNA polymerase II, a critical protein in gene expression, forms fleeting (“transient”) clusters with similar molecules in order to transcribe DNA into RNA. He joined the Department of Physics in 2014, and was recently granted tenure and a joint appointment in biology. He sat down to discuss how his physics training led him to rewrite the textbook on biology.

Q: How does your work revise conventional models describing how RNA polymerases carry out their cellular duties?

A: My interest in biology has always been curiosity-driven. As a physicist reading biology textbooks, I thought that transcription — the process by which DNA is made into RNA — was fully understood. It’s so basic, and the textbooks write about it with such confidence. Come to find out, most of what we know about the cell nucleus, where gene expression starts, comes from people studying these processes outside the cell, inside a test tube. I started to wonder: Do we actually know how they work in a living cell?

The textbook models say that when a specific gene is being activated, RNA polymerase and dozens of other molecules are recruited to the DNA to begin transcription. If you don’t look closely enough, the polymerases appear to be uniformly distributed and acting randomly throughout the nucleus. However, my single-molecule and “super-resolution” microscopy methods allowed me to see something different when I looked inside live cells: polymerase clusters, which are very dynamic. In the mid-’90s, people had observed similar clusters in so-called “fixed” cells that were chemically frozen. But these findings were dismissed as possible artifacts of the fixation procedure. However, when we saw these same protein clusters in living cells that were not treated with harsh chemicals, it suggested that the textbook explanation may be incomplete.

Q: How has your background in physics given you a unique perspective on the mechanics of living cells?

A: When I arrived at the University of Illinois at Urbana-Champaign to begin my PhD in physics, I hadn’t enrolled in a biology class since high school. I was really taken with the interdisciplinary work of one physics professor, Taekjip Ha, who became my PhD mentor. He had developed single-molecule fluorescence resonance energy transfer techniques, to study with unprecedented sensitivity when two biomolecules are close to each other and monitor the distance between them in real time.

Taekjip graciously accepted me into his lab despite my limited biology background, and I never looked back. His work mirrored my interest in condensed matter physics, but the material we were looking at wasn’t from the inanimate world, it was living matter.

Between 2006 and 2008, as I was working on my PhD, super-resolution microscopy really took off from the single-molecule microscopes I used in grad school. It was a natural progression, in my mind, to learn cell biology during my postdoc fellowship at École Normale Supérieure in Paris, and to try to visualize weak and transient interactions directly in living cells using single-molecule and super-resolution imaging. You could now pinpoint molecules with nanometer accuracy; you could “turn on” and “off” molecules to observe them individually and ensure there was no overlap between those that were side-by-side.

Thanks to these new techniques, we saw clusters of RNA polymerases in living cells for the first time during my postdoc, and I pushed the technique further to reveal the cluster dynamics. But the fact that you had to turn individual molecules on and off made it really hard to see these clusters assembling or disassembling. I didn’t want to trade temporal resolution for spatial resolution. So I came up with an approach called Time-Correlated Photoactivated Localization Microscopy (tcPALM). It allowed us to measure the lifetimes of these ephemeral polymerase clusters, and we found that they last just a few seconds.

Once I arrived at MIT, we wanted to test whether the clusters could be fleeting but still biologically relevant. We pushed a dual-color super-resolution technique where we correlated the clusters with gene activity. With RNA live-imaging experts at Howard Hughes Medical Institute’s Janelia Research Campus, Brian English and Tim Lionnet, and my postdoc, Wonki Cho, we found that roughly 80 to 100 polymerases form a cluster on a gene where transcription is about to start. Although the cluster is only there for a few seconds, that’s enough time to load a handful of polymerases and generate “bursts” of RNA transcription. In fact, there was a linear correlation between the clusters’ transient dynamics and the number of messenger RNAs made in each burst.

Q: What is it like to be a physicist working with biologists?

A: Even though I joined MIT as a physics hire, I was lucky enough to get lab space in Building 68 alongside amazing biologists. They were the perfect people to talk to about my crazy ideas. And it turned out that renowned researchers like Rick Young and Phil Sharp actually had similar theories. They had genomic evidence for clusters of gene regulators, which they call “super enhancers,” that we all thought could relate to what my lab was seeing. That’s led to hours of exciting discussions between our labs, and has evolved into one of my most rewarding collaborations — and revealed that clusters associate as tiny transcriptional condensates with properties of liquid droplets.

Now, students and postdocs in my lab are wondering about the clusters’ functions and mechanisms of action, and whether protein clustering extends beyond transcription. For instance, clustering could explain some aspects of neurodegeneration. One perplexing idea that came out of this work is that perhaps it gets harder for our cells to clear protein condensates as we age, leading to Parkinson’s, Alzheimer’s, and other diseases. It’s becoming clearer that physics may be just as important as biology for understanding how cells work. The physics of how condensates and droplets form in the inanimate world is increasingly helpful in determining how living cells can evolve to regulate the same process for specific biological functions like transcription. Nature uses physics in much more elaborate ways than we initially anticipated.

Nine MIT School of Science professors receive tenure for 2020

Professors earn tenure in the departments of Brain and Cognitive Sciences, Chemistry, Mathematics, and Physics.

School of Science
July 6, 2020

Beginning July 1, nine faculty members in the MIT School of Science have been granted tenure by MIT. They are appointed in the departments of Brain and Cognitive Sciences, Chemistry, Mathematics, and Physics.

Physicist Ibrahim Cisse investigates living cells to reveal and study collective behaviors and biomolecular phase transitions at the resolution of single molecules. The results of his work help determine how disruptions in genes can cause diseases like cancer. Cisse joined the Department of Physics in 2014 and now holds a joint appointment with the Department of Biology. His education includes a bachelor’s degree in physics from North Carolina Central University, concluded in 2004, and a doctoral degree in physics from the University of Illinois at Urbana-Champaign, achieved in 2009. He followed his PhD with a postdoc at the École Normale Supérieure of Paris and a research specialist appointment at the Howard Hughes Medical Institute’s Janelia Research Campus.

Jörn Dunkel is a physical applied mathematician. His research focuses on the mathematical description of complex nonlinear phenomena in a variety of fields, especially biophysics. The models he develops help predict dynamical behaviors and structure formation processes in developmental biology, fluid dynamics, and even knot strengths for sailing, rock climbing and construction. He joined the Department of Mathematics in 2013 after completing postdoctoral appointments at Oxford University and Cambridge University. He received diplomas in physics and mathematics from Humboldt University of Berlin in 2004 and 2005, respectively. The University of Augsburg awarded Dunkel a PhD in statistical physics in 2008.

A cognitive neuroscientist, Mehrdad Jazayeri studies the neurobiological underpinnings of mental functions such as planning, inference, and learning by analyzing brain signals in the lab and using theoretical and computational models, including artificial neural networks. He joined the Department of Brain and Cognitive Sciences in 2013. He achieved a BS in electrical engineering from the Sharif University of Technology in 1994, an MS in physiology at the University of Toronto in 2001, and a PhD in neuroscience from New York University in 2007. Prior to joining MIT, he was a postdoc at the University of Washington. Jazayeri is also an investigator at the McGovern Institute for Brain Research.

Yen-Jie Lee is an experimental particle physicist in the field of proton-proton and heavy-ion physics. Utilizing the Large Hadron Colliders, Lee explores matter in extreme conditions, providing new insight into strong interactions and what might have existed and occurred at the beginning of the universe and in distant star cores. His work on jets and heavy flavor particle production in nuclei collisions improves understanding of the quark-gluon plasma, predicted by quantum chromodynamics (QCD) calculations, and the structure of heavy nuclei. He also pioneered studies of high-density QCD with electron-position annihilation data. Lee joined the Department of Physics in 2013 after a fellowship at CERN and postdoc research at the Laboratory for Nuclear Science at MIT. His bachelor’s and master’s degrees were awarded by the National Taiwan University in 2002 and 2004, respectively, and his doctoral degree by MIT in 2011. Lee is a member of the Laboratory for Nuclear Science.

Josh McDermott investigates the sense of hearing. His research addresses both human and machine audition using tools from experimental psychology, engineering, and neuroscience. McDermott hopes to better understand the neural computation underlying human hearing, to improve devices to assist hearing impaired, and to enhance machine interpretation of sounds. Prior to joining MIT’s Department of Brain and Cognitive Sciences, he was awarded a BA in 1998 in brain and cognitive sciences by Harvard University, a master’s degree in computational neuroscience in 2000 by University College London, and a PhD in brain and cognitive sciences in 2006 by MIT. Between his doctoral time at MIT and returning as a faculty member, he was a postdoc at the University of Minnesota and New York University, and a visiting scientist at Oxford University. McDermott is also an associate investigator at the McGovern Institute for Brain Research and an investigator in the Center for Brains, Minds and Machines.

Solving environmental challenges by studying and manipulating chemical reactions is the focus of Yogesh Surendranath’s research. Using chemistry, he works at the molecular level to understand how to efficiently interconvert chemical and electrical energy. His fundamental studies aim to improve energy storage technologies, such as batteries, fuel cells, and electrolyzers, that can be used to meet future energy demand with reduced carbon emissions. Surendranath joined the Department of Chemistry in 2013 after a postdoc at the University of California at Berkeley. His PhD was completed in 2011 at MIT, and BS in 2006 at the University of Virginia. Suendranath is also a collaborator in the MIT Energy Initiative.

A theoretical astrophysicist, Mark Vogelsberger is interested in large-scale structures of the universe, such as galaxy formation. He combines observational data, theoretical models, and simulations that require high-performance supercomputers to improve and develop detailed models that simulate galaxy diversity, clustering, and their properties, including a plethora of physical effects like magnetic fields, cosmic dust, and thermal conduction. Vogelsberger also uses simulations to generate scenarios involving alternative forms of dark matter. He joined the Department of Physics in 2014 after a postdoc at the Harvard-Smithsonian Center for Astrophysics. Vogelsberger is a 2006 graduate of the University of Mainz undergraduate program in physics, and a 2010 doctoral graduate of the University of Munich and the Max Plank Institute for Astrophysics. He is also a principal investigator in the MIT Kavli Institute for Astrophysics and Space Research.

Adam Willard is a theoretical chemist with research interests that fall across molecular biology, renewable energy, and material science. He uses theory, modeling, and molecular simulation to study the disorder that is inherent to systems over nanometer-length scales. His recent work has highlighted the fundamental and unexpected role that such disorder plays in phenomena such as microscopic energy transport in semiconducting plastics, ion transport in batteries, and protein hydration. Joining the Department of Chemistry in 2013, Willard was formerly a postdoc at Lawrence Berkeley National Laboratory and then the University of Texas at Austin. He holds a PhD in chemistry from the University of California at Berkeley, achieved in 2009, and a BS in chemistry and mathematics from the University of Puget Sound, granted in 2003.

Lindley Winslow seeks to understand the fundamental particles shaped the evolution of our universe. As an experimental particle and nuclear physicist, she develops novel detection technology to search for axion dark matter and a proposed nuclear decay that makes more matter than antimatter. She started her faculty position in the Department of Physics in 2015 following a postdoc at MIT and a subsequent faculty position at the University of California at Los Angeles. Winslow achieved her BA in physics and astronomy in 2001 and PhD in physics in 2008, both at the University of California at Berkeley. She is also a member of the Laboratory for Nuclear Science.