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3 Questions: Nancy Hopkins on improving gender equality in academia

Molecular biologist and professor emerita advocates for more inclusive science and advises how to get there.

Raleigh McElvery | Department of Biology
September 30, 2020

Over the course of her exceptional career, Amgen Professor of Biology Emerita Nancy Hopkins has overturned assumptions and defied expectations at the lab bench and beyond. After arriving at MIT in 1973, she set to work mapping RNA tumor virus genes, before switching her focus and pioneering zebrafish as a model system to probe vertebrate development and cancer.

Her experiences in male-dominated fields and institutions led her to catalyze an investigation that evolved into the groundbreaking 1999 public report on the status of women at MIT. These findings spurred nine universities, including MIT, to establish an ongoing effort to improve gender equity. A recent documentary, “Picture a Scientist,” chronicles this watershed report and spotlights researchers like Hopkins who champion underrepresented voices. She sat down to discuss what has changed for women in academia in the last two decades — and what hasn’t.

Q: How has the situation for women in science evolved since the landmark 1999 report?

A: It’s hard today to remember just how radical the 1999 report was at the time. I read it now and think, ‘What was so radical about that?’

The report documented that women joined the faculty believing that only greater family responsibilities might impede their success relative to male colleagues. But, as they progressed through tenure, many were marginalized and undervalued. Data showed this resulted in women having fewer institutional resources and rewards for their research, and in their exclusion from important professional opportunities. When the study began, only 8% of the science faculty were women.

Former MIT Dean of Science Robert Birgeneau addressed inequities on a case-by-case basis, adjusting salaries, space, and resources. He recruited women aggressively, quickly increasing the number of women School of Science faculty by 50%.

When the report became public, the overwhelming public reaction made clear that it described problems that were epidemic among women in science, technology, engineering, and mathematics (STEM). Former MIT President Chuck Vest and Provost Bob Brown addressed gender bias for all of MIT and “institutionalized” solutions. They established committees in the five MIT schools to ensure that inequities were promptly addressed and hiring policies were fair; rewrote family leave policies with input from women faculty; built day care facilities on campus; and recruited women faculty to high-level administrative positions.

Today, we realize that the MIT report elucidated two underappreciated forms of bias: “institutional bias” resulting from a system designed for a man with a wife at home; and “unconscious or implicit gender bias.” Voluminous research by psychologists has documented the latter, showing that identical work is undervalued if people believe it was done by a woman. Refusal to acknowledge unconscious gender bias today is akin to denying the world is round.

Q: What do you hope people will take away from the “Picture a Scientist” film?

A: I hope people will better understand why women are underrepresented in science, and women of color particularly so. The film does a terrific job of portraying the range of destructive behaviors that collectively explain the question, “Why so few?” The movie also focuses on the courage it takes for young women scientists to expose these problems.

I hope people will agree that, despite all the progress for women in my generation, as the bombshell report from the National Academy of Sciences documented in 2018, sexual harassment and gender discrimination persist and still require constant attention. It remains a challenge to identify, attract, and retain the best STEM talent. And, as the movie points out, it’s critical to do so.

The producers have received an unprecedented number of requests to show the documentary in institutes, universities, and companies, confirming that underrepresentation remains a widespread and pressing issue.

Q: Where do we go from here? How can academia better support underrepresented groups in science moving forward?

A: People often say you have to “change the culture,” but what does that really mean? You have to do what MIT did: look at the data; make corrections, including policy changes if necessary; continue to track the data to see if the policies work; and repeat as needed. Second, as the National Academies report points out, you must reward administrators who create a diverse workplace. Top talent is distributed among diverse groups. You can only be the best by being diverse.

But how do you change the behavior of individual faculty? Years ago, President Vest told me, “Nancy, anything I can measure I can fix, but I don’t know how to fix marginalization.” His comment was prescient. We’re pretty good at fixing things we can measure. But not at retraining our own unconscious biases: preference for working with people who look just like us; and unexamined, biased assumptions about people different from us. But psychologists tell us all we have to do is ‘change the world and our biases will change along with it.’  Furthermore, they now have methods to measure change in our biases.

I championed this cause because I believe being a scientist is the greatest job there is. I want anyone with this passion to be able to be a scientist. I’m grateful I got to see change first hand. I just wish the change was faster, so young women like Jane Willenbring and Raychelle Burks in the movie can just be scientists.

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.

Type 1 diabetes from a beta cell’s perspective
Eva Frederick | Whitehead Institute
September 24, 2020

Type 1 diabetes is an autoimmune disease that occurs when T-cells in the immune system attack the body’s own insulin-producing cells, called beta cells, in the pancreas. Usually diagnosed in children and young adults, type 1 diabetes accounts for around five percent of all diabetes cases.

The underlying biology of type 1 diabetes is tricky to study for a number of reasons. For one thing, by the time a person begins to show symptoms, their T-cells have already been destroying beta cells for a long period — months or even years. Also, the initial trigger for the disease is often unclear; a number of beta cell proteins can set off the immune response.

In a study published Sept. 22 in Cell Reports Medicine, researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch demonstrate a new experimental system for more precisely studying the mechanisms of type 1 diabetes, focusing on how a person’s beta cells respond to an attack from their own immune system. In doing so, they reveal features of the disease that could be targets for future therapeutics.

“Here our question was, let’s say the T cells get activated; what happens next from the perspective of beta cells? Could we find some potential intervention opportunities?” said Haiting Ma, a postdoctoral associate in Jaenisch’s lab and the first author of the study.

Ma, working with Jaenisch, also a professor of biology at MIT, and Jacob Jeppesen, Novo Nordisk’s Head of Diabetes and Metabolism Biology, took a synthetic biology approach to achieve this goal.

The researchers engineered a system by inducing human pluripotent stem cells to differentiate into functional pancreatic beta cells, and added a model antigen called CD19 to these cells using CRISPR techniques. They established that these cells functioned as insulin-producing beta cells by implanting them in diabetic mice; upon receiving the cells, the mice experienced an improvement in glucose levels.

They then replicated the autoimmune components of the disease using engineered immune cells called CAR-T cells. CAR-T cells are T-cells tailor-made to attack a certain type of cell; for example, they can be targeted to tumor cells to treat certain types of cancer. For the diabetes model, the researchers engineered the cells to contain receptors for the model antigen CD19.

When the researchers cocultured the synthetic beta cells and CAR-T cells, they found the system worked well to mimic a simplified version of type 1 diabetes: the CAR-T cells attacked the beta cells and caused them to enter the process of cell death. The researchers were also able to implement the strategy in humanized mice.

Using their new experimental system, the researchers were able to identify some interesting factors involved in the beta cells’ response to diabetic conditions. For one thing, they found that the beta cells cranked up production of protective mechanisms such as the protein PDL1. PDL1 is a protein found on non-harmful cells in the body that, in normal circumstances, prevents the immune system from attacking them.

Changes in PDL1 levels had been associated with type 1 diabetes in previous studies. Now, Ma wondered if it was possible to rescue the beta cells from the immune onslaught by inducing the expression of even more of the helpful protein. “We found that we can help beta cells by giving them a higher expression of PDL1,” he said. “When we do this, they can do better in the model.” If validated in human cells, increasing expression of PDL1 could be evaluated as a potential therapeutic method, Ma said.

Another finding concerned the way the cells died after T-cell attack. Ma found that the genes that were being upregulated as the beta cells were under attack were associated not with the usual form of cell death, apoptosis, but with a more inflammatory and violent kind of cell death called pyroptosis.

“The interesting thing about pyroptosis is that it causes the cells to release their contents,” Ma said. “This is in contrast to apoptosis, which is considered to be the main mechanism for autoimmune response. We think that pyroptosis could play a role in propelling this autoimmune reaction, because the contents from beta cells include multiple potential antigens. If these are released, they can be picked out by antigen presenting cells and start to crank up this autoimmunity.”

The process of pyroptosis in the context of beta cell autoimmunity could be linked to ER stress in beta cells, a highly secretory cell type. Indeed, an ER stress inducing chemical increased the marker of pyroptosis.

If researchers could find a way to inhibit the process of pyroptosis safely in humans, it could potentially lessen the severity of the autoimmune reaction that is the hallmark of type 1 diabetes. Pyroptosis is mediated by a protein called caspase-4, which can be inhibited in the lab. “If that can be validated in patient beta cells, that could indicate that modulating caspases could also be [a therapeutic mechanism],” Ma said.

Going forward, Ma and Jaenisch plan to investigate the immune mechanisms underlying autoimmunity in humans by using induced pluripotent stem cells from patients with type 1 diabetes. “These cells could be differentiated into immune cells such as T, B, macrophage, and dendritic cells, and we can investigate how they interact with beta cells,” Ma said.

They also plan to keep improving their new experimental system. “This system provides a very robust and tractable synthetic immune response that we can use to study type 1 diabetes,” said Jaenisch. “In the future it could be used to study other autoimmune diseases.”

This study was supported by a generous gift from Liliana and Hillel Bachrach, a collaborative research agreement from Novo Nordisk, and NIH grant 1R01-NS088538 (to R.J.).

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Written by Eva Frederick

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Citation:

Ma, H., Jeppesen, J, and Jaenisch, R. “Human T-cells expressing a CD19 CAR-T receptor provide insights into mechanisms of human CD19 positive cell destruction.” Cell Reports Medicine. Sept 22. https://doi.org/10.1016/j.xcrm.2020.100097

These genes help explain how malaria parasites survive treatment with common drug
Eva Frederick | Whitehead Institute
September 23, 2020

The essential malaria drug artemisinin acts like a “ticking time bomb” in parasite cells — but in the half a century since the drug was introduced, malaria-causing parasites have slowly grown less and less susceptible to the treatment, threatening attempts at global control over the disease.

In a paper published September 23 in Nature Communications, Whitehead Institute Member Sebastian Lourido and colleagues use genome screening techniques in the related parasite Toxoplasma gondii (T. gondii) to identify genes that affect the parasites’ susceptibility to artemisinin. Two genes stood out in the screen: one that makes the drug more lethal, and another that helps the parasite survive the treatment.

Artemisinin is derived from the extract of sweet wormwood (Artemisia annua), and is usually used against malaria as part of a combination therapy. “Artemisinin kills malaria-causing parasites super fast—it will wipe out 90 percent of parasites within 24 hours,” says former postdoctoral researcher and co-first author Clare Harding, now a research fellow at the University of Glasgow. Once the fast-acting drug clears out the bulk of the parasites—such as Plasmodium falciparum, the culprit in the deadliest forms of malaria—from the bloodstream, the second drug finishes off the stragglers, curing the infection.

“Artemisinin works differently than most antibiotics,” Lourido said. “You can think of it as a sort of bomb that needs to be turned on in order to work.” The molecule required to light the drug’s fuse is called heme. Heme is a small molecule that facilitates several cellular functions, including electron transport and the delivery of oxygen to tissues as a component of hemoglobin. When heme molecules encounter artemisinin, they activate the drug allowing the creation of small, toxic radicals which react with proteins, lipids and metabolites inside the parasite, leading to its death.

Lourido, Harding, and co-first authors Boryana Petrova and Saima Sidik (“We were the ‘Heme Team,’” Harding said) wanted to understand what mechanisms the less susceptible parasites were using to avoid activating the “bomb”. Previously, Lourido and his lab—which focuses on apicomplexan parasites, a group which includes both Toxoplasma gondii and the malaria-causing Plasmodium falciparum—had developed a method to screen the entire genome of T. gondii to discover beneficial and harmful mutations. For a number of reasons, the screen does not work on Plasmodium parasites, but Lourido hypothesized that the related parasites’ genomes were similar enough that the method could prove helpful.

After running the screen, two genes stood out to the researchers as important factors in the parasites’ susceptibility to artemisinin treatment. One, called Tmem14c, seemed to be protecting the parasites: when the gene was disrupted in the screen, the parasites became more susceptible to treatment with artemisinin. The gene is analogous to one in red blood cells that serves as a transporter for heme and its building blocks, shuttling them in and out of the mitochondrion.

“What could be happening here is that, in the absence of Tmem14c, heme, artemisinin’s activator, collects within the mitochondria where it is being synthesized, thereby rendering the mitochondria better at activating that ticking time bomb,” Lourido said. “Having that high concentration of heme in the mitochondria is like having a flame when there is a gas leak.”

The screen also identified one mutation that led to parasites being less sensitive to artemisinin. The mutation affected a gene called DegP2, the product of which interacts with several mitochondrial proteins and appears to play a role in heme metabolism. When less DegP2 was present, the cells contained a lower amount of heme, which in turn made it less likely that the parasites would be killed by artemisinin.

Both the findings support other research suggesting that heme metabolism is crucial for artemisinin susceptibility. “It is important to consider the role of heme when combining artemisinin with other therapies,” Lourido said. “You would want to avoid combination therapy that might inadvertently suppress the level of heme within the parasite and thereby reduce susceptibility to antiparasitic agents.”

The project also showed the potential of using the Toxoplasma screening method as a model to study other related parasites. The screen confirmed findings in Toxoplasma that had previously been shown in Plasmodium, suggesting that it could be a valuable tool in studying malaria and other diseases caused by apicomplexan parasites.

“Through the amazing screens and molecular biology that you can do in Toxoplasma, we can really learn a lot about the biology of this diverse group of parasites,” Lourido said. “Defeating malaria is going to take a lot of different and creative approaches, and the fundamental research that we can do in Toxoplasma can in fact inform many of the critical clinical questions we need to answer to control this disease.”

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Written by Eva Frederick

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Harding, C., Sidik, S, and Petrova, B., et al. “Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility.” Nature Communications. DOI: https://doi.org/10.1038/s41467-020-18624-0

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.

AN UNEXPECTED DISCOVERY

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.

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Written by Greta Friar

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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.

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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; 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.