Bringing new energy to mitochondria research
Greta Friar | Whitehead Institute
September 17, 2020

Tiny mitochondria in our cells turn oxygen and nutrients into usable energy in a process called respiration. This process is essential for powering our cells, and yet in spite of its importance many of the finer details of how it happens remain unknown. One long-standing mystery is how a molecule called nicotinamide adenine dinucleotide (NAD), which plays a big part in respiration and metabolism, gets into the mitochondria in humans and other animals. Mitochondria use NAD in order to produce adenosine triphosphate (ATP), the energy supply molecules used throughout the cell. Researchers knew the identities of the molecules that transport NAD from the wider cell into the mitochondria of yeast and plants, but had not found the animal equivalent—in fact, there was some debate over whether one even existed or whether animal cells used other methods altogether.

Now, research from postdoctoral researcher Nora Kory in Whitehead Institute Member David Sabatini’s lab may end the debate. In a paper published in Science Advances on September 9, the researchers show that the missing human NAD transporter is likely the protein MCART1. This discovery not only answers a longstanding question about a vital cellular process, but may contribute to research on aging—during which cells’ NAD levels drop—as well as research on diseases that involve certain mitochondrial dysfunctions, for which cells with broken NAD transporters could be an experimental model.

“I find it striking that mitochondria play such an important role in metabolism in the cell, which in turn plays a huge role in health and disease, but we still don’t understand how all of the molecules involved get in and out of mitochondria. It was exciting to fill in a piece of that puzzle.” Kory says.

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Kory did not set out to find the long sought-after transport molecule. Rather, she was trying to better understand mitochondrial respiration by mapping the genes involved. She was comparing gene essentiality profiles, which show how important a gene is to different processes in a cell—the more co-essential two genes are, the more likely they are to be involved in the same cellular process—and one gene stood out: MCART1, also known as SLC25A51. It was highly correlated to other genes involved in mitochondrial respiration, and belonged to a family of genes known to code for transporters, yet its function was unknown. The protein coded for by MCART1 clearly played an important role, so Kory decided to figure out what that was; as her research progressed, she realized she had found the missing NAD transporter.

Kory and colleagues applied a common approach to determine MCART1’s function: inactivate the gene in cells, and see what breaks down in its absence. This approach is like troubleshooting a machine; if you cut a wire in your car and the headlights stop working, but everything else is fine, then that wire was probably linked to the headlights. When the researchers removed MCART1, the cells exhibited much lower oxygen consumption, reduced respiration and ATP production, and reliance on other, far less efficient means of ATP production—exactly what you’d expect to see if the inactivated gene was needed for respiration. Moreover, the biggest change that the researchers observed in cells without MCART1 was reduced levels of NAD in the mitochondria, while NAD levels in the wider cell remained the same, which they quantified using experiments previously developed in the lab. The researchers confirmed that MCART1 is essential for NAD transport into isolated mitochondria and overabundance of MCART1 caused an increased uptake.

“It’s very satisfying when our lab returns to the techniques that we have developed in order to make new findings such as identifying this important protein,” says Sabatini, who is also a professor of biology at Massachusetts Institute of Technology and an investigator with the Howard Hughes Medical Institute.

The evidence supports that the protein MCART1 is itself the transport channel. However, it is possible that the protein may play some other essential contributing role to transportation, or that it combines with other molecules to do its job. To strengthen the case for MCART1 as the transporter, the researchers showed that MCART1 and the known yeast NAD transport could be switched out for each other in both human and yeast cells, suggesting an equivalent function. Still, further experiments are needed to determine the precise mechanism of transport.

A serendipitous case of synchronous discovery reinforces Kory’s findings. A paper by other researchers published on the same day in the journal Nature also put forth that MCART1 is the missing NAD transporter, based on a completely different set of evidence. Combined, the papers provide an even more compelling case.

“It was nice to see how our different approaches complemented each other, and led to the same conclusion,” Kory says.

Understanding how NAD gets into the mitochondria opens up new questions about the details of mitochondrial respiration. Kory will shortly be leaving Sabatini’s lab to open her own lab at the Harvard T.H. Chan School of Public Health, where she intended to continue investigating the role of the mitochondria’s NAD supply in metabolism and signaling.

***

Written by Greta Friar

***

David Sabatini’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.

***

Citations:

Kory, N., et al. (2020). MCART1/SLC25A51 is required for mitochondrial NAD transport. Science Advances. doi:10.1126/sciadv.abe5310

Luongo, T. S., et al. (2020). SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature. doi:10.1038/s41586-020-2741-7

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; netbet sports betting appBrain 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 netbet sports bettingunknowns 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.

Defining a “new normal” for campus research

Despite the trials and tribulations of the COVID-19 pandemic, Building 68 core facilities have remained open for business.

Raleigh McElvery
September 10, 2020

In mid-March, MIT closed its doors due to the COVID-19 pandemic, and Building 68 temporarily became a ghost town. Home to over 25 life science labs and three core facilities, the Department of Biology’s primary research hub usually teems with activity. But this spring, only a skeleton crew of essential workers came in and out, maintaining the equipment and running select experiments. Since then, the ghost town has gradually come back to life, as scientists are returning to their benches once again while taking safety precautions.

Three of the 24 core facilities affiliated with the life sciences are located in Building 68: the BioMicro Center, Structural Biology Core Facility, and Biophysical Instrumentation Facility. Known fondly as the “BIF,” the latter houses instruments that help researchers elucidate macromolecular structures. Select staff members remained available throughout the research shutdown to help biologists, biological engineers, and chemists run essential protocols.

One floor down, the BioMicro Center also continued to offer limited services — from maintaining multi-year cancer studies to running analyses probing SARS-CoV-2, the virus strain that causes COVID-19. The team there specializes in genomic and transcriptomic technologies, bioinformatics, and research computing.

Stuart Levine SB ’97,  who leads the BioMicro Center, says the facility handled anywhere from six to nine projects a day before the pandemic. But during the research shutdown, requests dwindled netbet sports bettingto a steady “trickle.”

“We did whatever we could to be helpful,” he adds. “I went to campus a few times early on, and it was eerie to be one of the only people in the building.”

Illustration of virus-like molecule
Illustration of the Bathe lab’s virus-like nanoparticle. Credit: Ella Maru Design Studio

Although the BioMicro Center is situated in Building 68, it serves a wide array of individuals and labs across campus. Chemical engineering graduate student, Grant Knappe, was also among the select few permitted to work in lab during the shutdown, and he relied heavily on the BioMicro Center for a key step in his experimental protocol. Knappe’s advisor, Professor of Biological Engineering Mark Bathe, began shifting his group’s focus to COVID-related projects almost immediately after campus emptied in mid-March.

The Bathe lab studies nanoparticles made from DNA “origami” that’s been folded into tiny geometric shapes. They’ve developed user-friendly algorithms to design these structures, and regularly employ the BioMicro’s oligonucleotide synthesizer to produce their DNA strands. With the help of the facility, Knappe and his colleagues recently created nanoparticles adorned with short DNA strands to mimic the SARS-CoV-2 spike protein — which induces the body’s immune response. They hope these geometric nanoparticles will eventually help develop COVID-19 vaccines.

“The scientific process is usually very collaborative,” Knappe says, “so at the beginning it was difficult to run experiments without other people nearby to bounce ideas back-and-forth.”

Focusing on just one project — rather than several simultaneously — was also a new experience. Knappe is excited to see where his COVID research will go, and what lab instruments will ultimately be key to the process. “You never know what equipment could end up fighting the virus,” he adds.

On June 1, Phase 1 of the research ramp-up began, and labs were permitted to begin operating at 25% capacity. Scientists started working in shifts with reduced hours, conducting their experiments many feet apart, and visiting MIT Medical for regular COVID-19 testing. Levine remembers that the number of requests for BioMicro services surged almost immediately as researchers returned.

At the same time, Robert Grant, the Research Scientist responsible for the Structural Biology Core Facility, started up the core’s state-of-the-art X-ray crystallography equipment. Leaving in March had been a “mad scramble,” and he remembers hastily terminating non-essential experiments and distributing extra resources (like liquid nitrogen tanks) to labs in-need. When he returned in June he already had project requests.

“A big part of my job is interacting with people, which I really enjoy,” he says. “But we’ve had to adapt, and and devise new ways to train people on equipment and data processing that don’t require close contact.”

Grant has recently started socially distant one-on-one trainings, where both parties remain as far apart as possible while wearing masks and gloves. In some cases, he’s processed samples and collected data for users, helping them perform analyses via Zoom. He’s also found ways to revive collaborations with other institutes. He recently sent crystals to Argonne National Laboratory in Chicago. The student who grew the crystals then remotely controlled an X-ray beamline at Argonne’s Advanced Photon Source synchrotron to collect diffraction data from home while Zooming with Grant.

“We’re definitely open for business, although things look a little different than before,” Grant says. “We’ve reached a new normal.”

Building 68's Structural Biology Core Facility
Building 68’s Structural Biology Core Facility
Posted: 9.10.20
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 NetBet sportphenomena 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.

Sebastian Lourido earns ASM Award for Early Career Basic Research
August 28, 2020

Washington, D.C. – August 27, 2020 – The 2021 American Society for Microbiology (ASM) awardees in research, education and leadership have now been announced. ASM congratulates all of the award recipients for their achievements. The ASM Awards program is managed by the American Academy of Microbiology, the honorific leadership group within ASM. The mission of the Academy netbet online sports bettingis to recognize microbiologists for outstanding contributions to the microbial sciences and to provide microbiological expertise in the service of science and the public.

The 2021 ASM Award Laureates:

ASM Alice C. Evans Award for Advancement of Women
Recognizes outstanding contributions toward the full participation and advancement of women in the microbial sciences. This award is given in memory of Alice C. Evans, the first woman to be elected ASM president (elected in 1928).
•    Jennifer Glass, Ph.D.

ASM Award for Applied and Biotechnological Research
Recognizes an outstanding scientist with distinguished research achievements in the development of products, processes and technologies that have advanced the microbial sciences.
•    Dennis Hruby, Ph.D.

ASM Award for Early Career Applied and Biotechnological Research
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“Runaway” Transcription

Researchers discover new rules governing bacterial gene expression that overturn fundamental assumptions about basic biological pathways.

Raleigh McElvery
August 26, 2020

On the evolutionary tree, humans diverged from yeast roughly one billion years ago. By comparison, two seemingly similar species of bacteria, Escherichia coli and Bacillus subtilis, have been evolving apart for roughly twice as long. In other words: walking, talking bipeds are closer on the tree of life to single-celled fungus than these two bacteria are to one another. In fact, it’s becoming increasingly clear that what is true of one bacterial type may not be true of another — even when it comes down to life’s most basic biological pathways.

E. coli has served as a model organism in scientific research for over a century, and helped researchers parse many fundamental processes, including gene expression. In these bacteria, as one molecular machine, the RNA polymerase, moves along the DNA transcribing it into RNA, it is followed in close pursuit by a second molecular machine, the ribosome, which translates the RNA into proteins. This “coupled” transcription-translation helps monitor and tune RNA output, and is considered a hallmark of bacteria.

However, an interdisciplinary team of biologists and physicists recently showed that the B. subtilis bacterium employs a different set of rules. Rather than working in tandem with the ribosome, the polymerase in B. subtilis speeds ahead. This system of “runaway” transcription creates alternative rules for RNA quality control, and provides insights into the sheer diversity of bacterial species.

“Generations of researchers, including myself, were taught that coupled transcription-translation is fundamental to bacterial gene expression,” says Gene-Wei Li, an associate professor of biology and senior author of the study. “But our very precise, quantitative measurements have overturned that long-held view, and this study could be just the tip of the iceberg.”

Grace Johnson, a graduate student in the Department of Biology, and Jean-Benoît Lalanne, a graduate student in the Department of Physics, are the lead authors on the paper, which appeared in Nature on Aug. 26.

A curious clue

In 2018, Lalanne developed an experimental technique to measure the boundaries of RNA transcripts. When DNA is transcribed into RNA, the resulting transcripts are generally longer than the DNA coding sequence because they also have to include an extra bit at the end to signal the polymerase to stop. In B. subtilis, Lalanne noticed there simply wasn’t enough space between the ends of the coding sequences and the ends of the RNA transcripts — the extra code was too short for both the polymerase and the ribosome to fit at the same time. In this bacterium, coupled transcription-translation didn’t seem possible.

“It was a pretty weird observation,” Lalanne recalls. “It just didn’t square up with the accepted dogma.”

To delve further into these puzzling observations, Johnson measured the speeds of the RNA polymerase and ribosome in B. subtilis. She was surprised to find that they were moving at very different rates: the polymerase was going roughly twice as fast as the ribosome.

During coupled transcription-translation in E. coli, the ribosome is so closely associated with the RNA polymerase that it can control when transcription terminates. If the RNA encodes a “premature” signal for the polymerase to stop transcribing, the nearby ribosome can mask it and spur the polymerase on. However, if something goes awry and the ribosome is halted too far behind the polymerase, a protein called Rho can intervene netbet online sports bettingto terminate transcription at these premature sites, halting the production of these presumably non-functional transcripts.

However, in B. subtilis, the ribosome is always too far behind the polymerase to exert its masking effect. Instead, Johnson found that Rho recognizes signals encoded in the RNA itself. This allows Rho to prevent production of select RNAs while ensuring it doesn’t suppress all RNAs. However, these specific signals also mean Rho likely has a more limited role in B. subtilis than it does in E. coli.

A family trait

To gauge how common runaway transcription is, Lalanne created algorithms that sifted through genomes from over 1,000 bacterial species to identify the ends of transcripts. In many cases, there was not enough space at the end of the transcripts for both the RNA polymerase and the ribosome to fit, indicating that more than 200 additional bacteria also rely on runaway transcription.

“It was striking to see just how widespread this phenomenon is,” Li says. “It raises the question: How much do we really know about these model organisms we’ve been studying for so many years?”

Carol Gross, a professor in the Department of Microbiology and Immunology at University of California San Francisco who was not involved with the study, refers to the work as a “tour de force.”

“Gene-Wei Li and colleagues show transcription-translation coupling, thought to be a foundational feature of bacterial gene regulation, is not universal,” she says. “Instead, runaway transcription leads to a host of alternative regulatory strategies, thereby opening a new frontier in our study of bacterial strategies to thrive in varied environments.”

As researchers widen their experimental radius to include more types of bacteria, they are learning more about the basic biological processes underlying these microorganisms — with implications for those that take up residence in the human body, from helpful gut microbes to noxious pathogens.

“We’re beginning to realize that bacteria can have distinct ways of regulating gene expression and responding to environmental stress,” Johnson says. “It just shows how much interesting biology is left to uncover as we study increasingly diverse bacteria.”

Citation:
“Functionally uncoupled transcription–translation in Bacillus subtilis
Nature, online August 26, 2020, DOI: 10.1038/s41586-020-2638-5
Grace E. Johnson, Jean-Benoît Lalanne, Michelle L. Peters, and Gene-Wei Li

Top illustration: Researchers discovered a new system of transcription and translation in bacteria, where the polymerase (pink) in B. subtilis “runs away” from the ribosome (blue). Credit: Grace Johnson
Posted: 8.26.20