Author: mantulin

3 Questions: Phillip Sharp on the discoveries that enabled RNA vaccines for Covid-19

Curiosity-driven basic science in the 1970s laid the groundwork for today’s leading vaccines against the novel coronavirus.

School of Science
December 11, 2020

Some of the most promising vaccines developed to combat Covid-19 rely on messenger RNA (mRNA) — a template cells use to carry genetic instructions for producing proteins. The mRNA vaccines take advantage of this cellular process to make proteins that then trigger an immune response that targets SARS-CoV-2, the virus that causes Covid-19.

Compared to other types of vaccines, recently developed technologies allow mRNA vaccines to be rapidly created and deployed on a large-scale — crucial aspects in the fight against Covid-19. Within the year since the identification and sequencing of the SARS-CoV-2 virus, companies such as Pfizer and Moderna have developed mRNA vaccines and run large-scale trials in the race to have a vaccine approved by the U.S. Food and Drug Administration — a feat unheard of with traditional vaccines using live attenuated or inactive viruses. These vaccines appear to have a greater than 90 percent efficacy in protecting against infection.

The fact that these vaccines could be rapidly developed within these last 10 months rests on more than four decades of study of mRNA. This success story begins with Institute Professor Phillip A. Sharp’s discovery of split genes and spliced RNA that took place at MIT in the 1970s — a discovery that would earn him the 1993 Nobel Prize in Physiology or Medicine.

Sharp, a professor within the Department of Biology and member of the Koch Institute for Integrative Cancer Research at MIT, commented on the long arc of scientific research that has led to this groundbreaking, rapid vaccine development — and looked ahead to what the future might hold for mRNA technology.

Q: Professor Sharp, take us back to the fifth floor of the MIT Center for Cancer Research in the 1970s. Were you and your colleagues thinking about vaccines when you studied viruses that caused cancer?

A: Not RNA vaccines! There was a hope in the ’70s that viruses were the cause of many cancers and could possibly be treated by conventional vaccination with inactivated virus. This is not the case, except for a few cancers such as HPV causing cervical cancer.

Also, not all groups at the MIT Center for Cancer Research (CCR) focused directly on cancer. We knew so little about the causes of cancer that Professor Salvador Luria, director of the CCR, recruited faculty to study cells and cancer at the most fundamental level. The center’s three focuses were virus and genetics, cell biology, and immunology. These were great choices.

Our research was initially funded by the American Cancer Society, and we later received federal funding from the National Cancer Institute, part of the National Institutes of Health and the National Science Foundation — as well as support from MIT through the CCR, of course.

At Cold Spring Harbor Laboratory in collaboration with colleagues, we had mapped the parts of the adenovirus genome responsible for tumor development. While doing so, I became intrigued by the report that adenovirus RNA in the nucleus was longer than the RNA found outside the nucleus in the cytoplasm where the messenger RNA was being translated into proteins. Other scientists had also described longer-than-expected nuclear RNA from cellular genes, and this seemed to be a fundamental puzzle to solve.

Susan Berget, a postdoc in my lab, and Claire Moore, a technician who ran MIT’s electron microscopy facility for the cancer center and would later be a postdoc in my lab, were instrumental in designing the experiments that would lead to the iconic electron micrograph that was the key to unlocking the mystery of this “heterogeneous” nuclear RNA. Since those days, Sue and Claire have had successful careers as professors at Baylor College of Medicine and Tufts Medical School, respectively.

The micrograph showed loops that would later be called “introns” — unnecessary extra material in between the relevant segments of mRNA, or “exons.” These exons would be joined together, or spliced, to create the final, shorter message for the translation to proteins in the cytoplasm of the cell.

This data was first presented at the Cancer Center fifth floor group meeting that included Bob Weinberg, David Baltimore, David Housman, and Nancy Hopkins. Their comments, particularly those of David Baltimore, were catalysts in our discovery. Our curiosity to understand this basic cellular mechanism drove us to learn more, to design the experiments that could elucidate the RNA splicing process. The collaborative environment of the MIT Cancer Center allowed us to share ideas and push each other to see problems in a new way.

Q: Your discovery of RNA splicing was a turning point, opening up new avenues that led to new applications. What did this foundation allow you to do that you couldn’t do before?

A: Our discovery in 1977 occurred just as biotechnology appeared with the objective of introducing complex human proteins as therapeutic agents, for example interferons and antibodies. Engineering genes to express these proteins in industrial tanks was dependent on this discovery of gene structure. The same is true of the RNA vaccines for Covid-19: By harnessing new technology for synthesis of RNA, researchers have developed vaccines whose chemical structure mimics that of cytoplasmic mRNA.

In the early 1980s, following isolation of many human mutant disease genes, we recognized that about one-fifth of these were defective for accurate RNA splicing. Further, we also found that different isoforms of mRNAs encoding different proteins can be generated from a single gene. This is “alternative RNA splicing” and may explain the puzzle that humans have fewer genes — 21,000 to 23,000 — than many less complex organisms, but these genes are expressed in more complex protein isoforms. This is just speculation, but there are so many things about biology yet to be discovered.

I liken RNA splicing to discovering the Rosetta Stone. We understood how the same letters of the alphabet could be written and rewritten to form new words, new meaning, and new languages. The new “language” of mRNA vaccines can be developed in a laboratory using a DNA template and readily available materials. Knowing the genetic code of the SARS-CoV-2 is the first step in generating the mRNA vaccine. The effective delivery of vaccines into the body based on our fundamental understanding of mRNA took decades more work and ingenuity to figure out how to evade other cellular mechanisms perfected over hundreds of millions of years of evolution to destroy foreign genetic material.

Q: Looking ahead 40 more years, where do you think mRNA technology might be?

A: In the future, mRNA vaccine technology may allow for one vaccine to target multiple diseases. We could also create personalized vaccines based on individuals’ genomes.

Messenger RNA vaccines have several benefits compared to other types of vaccines, including the use of noninfectious elements and shorter manufacturing times. The process can scaled up, making vaccine development faster than traditional methods. RNA vaccines can also be moved rapidly into clinical trials, which is critical for the next pandemic.

It is impossible to predict the future of RNA therapies, such as the new vaccines, but there are some signs that new advancements could happen very quickly. A few years ago, the first RNA-based therapy was approved for treatment of lethal genetic disease. This treatment was designed through the discovery of RNA interference. Messenger RNA-based therapies will also likely be used to treat genetic diseases, vaccinate against cancer, and generate transplantable organs. It is another tool at the forefront of modern medical care.

But keep in mind that all mRNAs in human cells are encoded by only 2 percent of the total genome sequence. Most of the other 98 percent is transcribed into cellular RNAs whose activities remain to be discovered. There could be many future RNA-based therapies.

MIT labs win top recognition for sustainable practices in cold storage management

Whitehead Institute and MIT named 2020 Organizational Winners in the fourth annual International Institute for Sustainable Laboratories International Laboratory Freezer Challenge.

Environment, Health and Safety Office
December 9, 2020

In its fourth year, the International Institute for Sustainable Laboratories (I2SL) International Laboratory Freezer Challenge drew 218 laboratory participants from around the world, from 88 research institutions. Three MIT laboratories participated in the challenge: the Department of Biology’s Barbara Imperiali Lab, Department of Biological Engineering’s Jacquin Niles Lab, and Department of Biology/Whitehead Institute for Biomedical Research’s David Sabatini Lab. MIT and the Whitehead Institute together received the Top Academic Organization Award. The Niles lab and the Imperiali lab are MIT Environment, Health & Safety (EHS) Green Lab Certified.

The Freezer Challenge, which is run by the nonprofit organizations My Green Labs and I2SL, is aimed at promoting efficient, effective sample storage for laboratories around the world, and using a spirit of friendly competition to increase sample accessibility, sample integrity, reduced costs, and energy efficiency.

Over a five-month period, challenge contestants implement optimal cold storage management practices, such as defrosting and removing dust from freezer intake or coils, regular cleanouts, organization of inventory on file, and high-density storage. Winners are then chosen based on the amount of energy saved. Additionally, in the spirit of friendly competition and collaboration that pervades the challenge, contestants can earn points for sharing tips about their own cold storage best practices.

This year, the 218 laboratory participants saved an estimated total of 3.2 million kilowatt-hours (kWh) per year, up from 2.4 million in 2019. The savings represents the equivalent of reducing carbon emissions by 2,260 metric tons per year, or removing 360 passenger vehicles from the road for a year. According to Christina Greever, operations manager at My Green Labs, the three participating MIT and Whitehead Institute labs saved an estimated 520 kWh/year.

Two of the three labs — Niles and Imperiali — have previously participated in MIT EHS’ Green Labs Freezer Challenge, and have consequently instituted good management practices surrounding cold storage. The Sabatini lab hasn’t previously participated in EHS’ challenge, but had also already implemented many of the practices the challenge encourages and rewards.

Edith Valeri, of the Sabatini lab, said that while her lab didn’t face any major difficulties, the challenge encouraged lab management staff to be “more aware of freezer usage” and “more mindful of wattage usage, turning down temperatures to a sustainable level, and defrosting the freezers.”

Similarly, both Sebastian Smick, a technical associate in the Niles lab, and Christine Arbour, an NIH postdoc in the Imperiali lab, found that participating in the challenge was not disruptive to operations, and the only difficulties they ran into came as a result of the Covid response. Because of their previous participation in  the MIT EHS’ Green Labs Freezer Challenge, efficient energy usage is already routine for the three labs.

Smick described the challenge as “a good incentive” for the Niles lab to practice regular thawing, and “a nice way to quantify what it means to the University’s power consumption.” He credits MIT Custodial Services for the invaluable support they provide on a regular basis. “Custodial Services is always there for us during our thaws to provide mopping and absorbent barriers while we thaw. Most of the ice is captured as a solid, but spillover is unavoidable. They’ve saved us thousands of paper towels!”

The Imperiali lab upgraded its cold storage in March, replacing its minus-80 degrees Celsius freezer with a newer, more energy efficient model, and entered the challenge ready to focus on maximizing that investment. “Our lab consistently cleans our freezer filters, -80 degree C freezer in particular, to prevent the compressor from overworking,” says Arbour. “We are also vigilant with appropriate chemical storage. We store chemicals at the temperature that the supplier/company recommends and nothing colder. This prevents overcrowding in –20 and –80 degree C freezers, which can start to add up!”

For Smick, a key takeaway from the challenge was the quantification of the power consumption of his lab’s cold storage. “I was so surprised when I first learned about the power consumption of our -80 C and -20 freezers,” he recalls. “It’s easy to see the impact of changing to a cheaper reagent or eliminating a wasteful process when it is something that comes directly out of your pocket, but electricity is something we take for granted; it should be conserved like any natural resource, and this challenge really shines an environmentally friendly, zero-energy consumption light on how easy it is to make a huge impact.”

Smick credits the challenge with inspiring his lab to conduct regular thaws, a major energy-saving practice. “I know for a fact that, prior to our regular freezer thaws which we started doing because of this competition, we were throwing away thousands of dollars of reagents away each year because they were lost in the glaciers that we were maintaining in our freezers.”

Similarly, Arbour says the Imperiali lab will continue to implement the practices recognized in the challenge. “Our lab practices will continue to evolve with new green practices,” she says. “Our entire lab is invested in doing better for the environment.”

“My hope is that competitions like this inspire MIT and the entire world to take a more serious look about how we deal with the resources available to us: from electricity to recyclable waste,” says Smick. “Science generates a huge amount of waste, and there is so much more that we can do to reduce environmental impact, and to offset the cost of generating meaningful data.”

MIT EHS has plans in the works for the enhancement and expansion of the Institute’s Green Labs program, and will be implementing them in the upcoming year. Labs interested in learning more about the Green Labs program, its benefits, and details on how to participate should contact environment@mit.edu.

Six MIT faculty elected 2020 AAAS Fellows

Choucri, Drennan, Fisher, Gershenfeld, Li, and Rus are recognized for their efforts to advance science.

MIT News Office
November 24, 2020

Six MIT faculty members have been elected as fellows of the American Association for the Advancement of Science (AAAS).

The new fellows are among a group of 489 AAAS members elected by their peers in recognition of their scientifically or socially distinguished efforts to advance science.

A virtual induction ceremony for the new fellows will be held on Feb. 13, 2021. 

Nazli Choucri is a professor of political science, a senior faculty member at the Center of International Studies (CIS), and a faculty affiliate at the Institute for Data, Science, and Society (IDSS). She works in the areas of international relations, conflict and violence, and the international political economy, with a focus on cyberspace and the global environment. Her current research is on cyberpolitics in international relations, focusing on linking integrating cyberspace into the fabric of international relations.

Catherine Drennan is a professor in the departments of Biology and Chemistry. Her research group seeks to understand how nature harnesses and redirects the reactivity of enzyme metallocenters in order to perform challenging reactions. By combining X-ray crystallography with other biophysical methods, the researchers’ goal is to “visualize” molecular processes by obtaining snapshots of enzymes in action.

Peter Fisher is a professor in the Department of Physics and currently serves as department head. He carries out research in particle physics in the areas of dark matter detection and the development of new kinds of particle detectors. He is also interested in compact energy supplies and wireless energy transmission.

Neil Gershenfeld is the director of MIT’s Center for Bits and Atoms, which works to break down boundaries between the digital and physical worlds, from pioneering quantum computing to digital fabrication to the “internet of things.” He is the founder of a global network of over 1,000 fab labs, chairs the Fab Foundation, and leads the Fab Academy.

Ju Li is the Battelle Energy Alliance Professor of Nuclear Science and Engineering and a professor of materials science and engineering. He studies how atoms and electrons behave and interact, to inform the design new materials from the atomic level on up. His research areas include overcoming timescale challenges in atomistic simulations, energy storage and conversion, and materials in extreme environments and far from equilibrium.

Daniela Rus is the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science and director of the Computer Science and Artificial Intelligence Laboratory (CSAIL) at MIT. Her research interests include robotics, mobile computing, and data science. Rus is a Class of 2002 MacArthur Fellow, a fellow of ACM, AAAI and IEEE, and a member of the National Academy of Engineering, and the American Academy for Arts and Science.

This year’s fellows will be formally announced in the AAAS News and Notes section of Science on Nov. 27.

Aspiring physician explores the many levels of human health

During her time at MIT, senior Ayesha Ng’s interests have expanded from cellular biology to the social systems that shape public health.

Alison Gold | School of Science
November 9, 2020

It was her childhood peanut allergy that first sparked senior Ayesha Ng’s fascination with the human body. “To see this severe reaction happen to my body and not know what was happening — that made me a lot more curious about biology and living systems,” Ng says.

She didn’t exactly plan it this way. But in her three and a half years at MIT, Ng, a biology and cognitive and brain sciences double major from the Los Angeles, California area, has conducted research and taken classes examining just about every level of human health — from cellular to societal.

Most recently, her passion for medicine and health equity led her to the National Foundation for the Centers for Disease Control and Prevention (CDC), where, this summer, she worked to develop guidelines for addressing health disparities on state and local health jurisdictions’ Covid-19 data dashboards. Now, as an aspiring physician amidst the medical school application process, Ng has a sense of how microbiological, physiological, and social systems interact to affect a person’s health.

Starting small

Throughout her entire first year at MIT, Ng studied the biology of health at a cellular level. Specifically, she researched the effects of fasting and aging on regeneration of intestinal stem cells, which are located in the human intestinal crypts and continuously self-divide and reproduce. Understanding these metabolic mechanisms is crucial, as their deregulation can lead to age-associated diseases such as cancer.

“That experience allowed me to broaden my technical skills, just getting used to so many different types of molecular biological techniques right away, which I really appreciated,” Ng says of her time at the Whitehead Institute for Biomedical Research in Professor David Sabatini’s lab.

“After some time, I realized that I also wanted to also study sciences at a broader, more macro level, instead of only the microbiology and molecular biology that we were studying in Course 7,” Ng says of her biology major.

In addition to studying the biology of cancer, Ng had developed a curiosity about the human brain and how it functions. “I was really interested in that, because my grandpa has dementia,” Ng says.

Seeing her grandfather’s cognitive decline, she was inspired to become involved in MIT BrainTrust, a student organization that offers a social support network for individuals from around the Boston, Massachusetts area who have brain injuries. “We have these meetings, in which I serve as one of only one or two students there to facilitate a safe space where we can have all these individuals with brain injury gather,” Ng says of the peer-support aspect of the program. “They can really share their mutual challenges and experiences.”

Investigating the brain

To pursue her interest in brain research and the societal impact of brain injuries, Ng traveled to the University of Hong Kong the summer after her first year as an MIT International Science and Technology Initiatives (MISTI) China Fung Scholar. Working with Professor Raymond Chang, she began to examine neurodegenerative disease and used tissue-clearing techniques to visualize 3D mouse brain structures at cellular resolution. “That was personally meaningful for me, to research about that and learn more about dementia,” Ng says.

Returning to MIT her sophomore year, Ng was certain that she wanted to continue studying the brain. She began working on Alzheimer’s research at the MIT Picower Institute for Learning and Memory in the lab of Professor Li-Huei Tsai, the Picower Professor of Neuroscience at MIT. Much existing research into Alzheimer’s disease has been at the bulk-tissue level, focusing on the neurons’ role in neurodegeneration associated with aging.

Ng’s work with Tsai considers the complexity of alterations across genes and less-abundant cell types, such as microglia, astrocytes, and other supporting glial cells that become dysregulated in the brains of patients with Alzheimer’s. Considering the interplay between and within cell types during neurodegeneration is most intriguing to her. While some molecular processes are protective, other damaging ones simultaneously occur and can exist even within the same cell type. This intricacy has made the mechanistic basis behind Alzheimer’s progression elusive and the research that much more crucial.

“It’s really interesting to see how heterogeneous and complex the responses are in Alzheimer’s brains,” Ng says of the research program with Tsai, a founding director of MIT’s Aging Brain Initiative. “I really think about these potential new drug targets to improve treatment for Alzheimer’s in the future because I have seen, with my grandpa especially, how treatment is really lacking in the neurodegeneration field. There’s no treatment that’s been able to stop or even slow the progression of Alzheimer’s disease.”

Her research project in the Tsai Lab relies on a technology called single-nucleus RNA sequencing (snRNA-seq), which extracts the genomic information contained in individual cells. This is followed by computational dimension reduction and clustering algorithms to examine how Alzheimer’s disease differentially affects genes and specific cell types.

“With that project, we’ve been able to use single-nucleus RNA sequencing to really look at the brains of human Alzheimer’s patients,” Ng says. “And with the single-cell technology, we’re able to look at brain tissue at a much higher resolution, allowing us to see that there’s so much heterogeneity within the brain.”

After conducting more than a year of Alzheimer’s research and then taking a human physiology class in her third year, Ng decided to add a second major in brain and cognitive sciences to gain deeper insight specifically into how the nervous system within the body functions.

“That class really allowed me to realize that I really love organ systems and wanted to study by looking at more physiological mechanisms,” Ng says. “It has been really great to, at the end of my college career, really delve more into a very specific system.”

Medicine and society

Having gained perspective on cellular and microbiology, and human organ systems, Ng decided to zoom out further, interning this past summer at the National Foundation for the CDC. She found the opportunity through MIT’s PKG Center, applied as one of 60 candidates, and was selected for a team of four. There, as a member of the CDC Foundation’s Health Equity Strike Team, she examined how to increase transparency of publicly available Covid-19 data on health disparities and how the narrative tied to health equity can be modified in public health messages. This involved harnessing data about the demographics of those most affected during Covid-19 — including how infection and mortality rates differ starkly based on social factors including housing conditions, socioeconomic status, race, and ethnicity.

“Thinking about all these factors, we compiled a set of best practices for how to present data about Covid-19, what data should be collected, and tried to push those out to help jurisdictions as best-practice recommendations,” Ng says. “That did really increase my interest in health equity and made me realize how important public health is as well.”

Amidst the Covid-19 pandemic, Ng is spending the first semester of her senior year at home with her family in the Los Angeles area. “I really miss the people and not being able to interact with not only other students and peers, but also faculty as well,” she says. “I really wanted to enjoy time with friends, and just explore more of MIT, too, which I didn’t always get the chance to do over the past few years.”

Still, she continues to participate in both BrainTrust and MIT’s Asian Dance team, remotely, through weekly practices on Zoom.

“I think dance is one of the biggest de-stressors for me; I had never done dance before going to college. Getting to meet this team and join this community allowed me not only to connect to my Asian cultural roots, but also just expose myself to this new art form where I could really learn how to express myself on stage,” Ng says. “And that really has been the source of relief for me to just liberate any worries that I have, and has increased my sense of self-awareness and self-confidence.”

Armed with the many experiences she has enjoyed at MIT, both in and out of the classroom, Ng plans to continue studying both medicine and public health. She’s excited to explore different potential specialties and is currently most intrigued by surgery. Whichever specialty she may choose, she is determined to include health equity and cultural sensitivity in her practice.

“Seeing surgeons, I personally think that being able to physically heal a patient with my own hands, that would be the most rewarding feeling,” Ng says. “I will strive to, as a physician, use whatever platform that I have to advocate for patients and really drive health-care systems to overcome disparities.”

Angelika Amon, cell biologist who pioneered research on chromosome imbalance, dies at 53

Professor and mentor for more than 20 years at MIT redefined scientists’ understanding of the biology of cell division and proliferation.

Bendta Schroeder | Koch Institute
October 30, 2020

Angelika Amon, professor of biology and a member of the Koch Institute for Integrative Cancer Research, died on Oct. 29 at age 53, following a two-and-a-half-year battle with ovarian cancer.

“Known for her piercing scientific insight and infectious enthusiasm for the deepest questions of science, Professor Amon built an extraordinary career – and in the process, a devoted community of colleagues, students and friends,” MIT President L. Rafael Reif wrote in a letter to the MIT community.

“Angelika was a force of nature and a highly valued member of our community,” reflects Tyler Jacks, the David H. Koch Professor of Biology at MIT and director of the Koch Institute. “Her intellect and wit were equally sharp, and she brought unmatched passion to everything she did. Through her groundbreaking research, her mentorship of so many, her teaching, and a host of other contributions, Angelika has made an incredible impact on the world — one that will last long into the future.”

A pioneer in cell biology

From the earliest stages of her career, Amon made profound contributions to our understanding of the fundamental biology of the cell, deciphering the regulatory networks that govern cell division and proliferation in yeast, mice, and mammalian organoids, and shedding light on the causes of chromosome mis-segregation and its consequences for human diseases.

Human cells have 23 pairs of chromosomes, but as they divide they can make errors that lead to too many or too few chromosomes, resulting in aneuploidy. Amon’s meticulous and rigorous experiments, first in yeast and then in mammalian cells, helped to uncover the biological consequences of having too many chromosomes. Her studies determined that extra chromosomes significantly impact the composition of the cell, causing stress in important processes such as protein folding and metabolism, and leading to additional mistakes that could drive cancer. Although stress resulting from aneuploidy affects cells’ ability to survive and proliferate, cancer cells — which are nearly universally aneuploid — can grow uncontrollably. Amon showed that aneuploidy disrupts cells’ usual error-repair systems, allowing genetic mutations to quickly accumulate.

Aneuploidy is usually fatal, but in some instances extra copies of specific chromosomes can lead to conditions such as Down syndrome and developmental disorders including those known as Patau and Edwards syndromes. This led Amon to work to understand how these negative effects result in some of the health problems associated specifically with Down syndrome, such as acute lymphoblastic leukemia. Her expertise in this area led her to be named co-director of the recently established Alana Down Syndrome Center at MIT.

“Angelika’s intellect and research were as astonishing as her bravery and her spirit. Her lab’s fundamental work on aneuploidy was integral to our establishment of the center,” say Li-Huei Tsai, the Picower Professor of Neuroscience and co-director of the Alana Down Syndrome Center. “Her exploration of the myriad consequences of aneuploidy for human health was vitally important and will continue to guide scientific and medical research.”

Another major focus of research in the Amon lab has been on the relationship between how cells grow, divide, and age. Among other insights, this work has revealed that once cells reach a certain large size, they lose the ability to proliferate and are unable to reenter the cell cycle. Further, this growth contributes to senescence, an irreversible cell cycle arrest, and tissue aging. In related work, Amon has investigated the relationships between stem cell size, stem cell function, and tissue age. Her lab’s studies have found that in hematopoetic stem cells, small size is important to cells’ ability to function and proliferate — in fact, she posted recent findings on bioRxiv earlier this week — and have been examining the same questions in epithelial cells as well.

Amon lab experiments delved deep into the mechanics of the biology, trying to understand the mechanisms behind their observations. To support this work, she established research collaborations to leverage approaches and technologies developed by her colleagues at the Koch Institute, including sophisticated intestinal organoid and mouse models developed by the Yilmaz Laboratory, and a microfluidic device developed by the Manalis Laboratory for measuring physical characteristics of single cells.

The thrill of discovery

Born in 1967, Amon grew up in Vienna, Austria, in a family of five. Playing outside all day with her three younger siblings, she developed an early love of biology and animals. She could not remember a time when she was not interested in biology, initially wanting to become a zoologist. But in high school, she saw an old black-and-white film from the 1950s about chromosome segregation, and found the moment that the sister chromatids split apart breathtaking. She knew then that she wanted to study the inner workings of the cell and decided to focus on genetics at the University of Vienna in Austria.

After receiving her BS, Amon continued her doctoral work there under Professor Kim Nasmyth at the Research Institute of Molecular Pathology, earning her PhD in 1993. From the outset, she made important contributions to the field of cell cycle dynamics. Her work on yeast genetics in the Nasmyth laboratory led to major discoveries about how one stage of the cell cycle sets up for the next, revealing that cyclins, proteins that accumulate within cells as they enter mitosis, must be broken down before cells pass from mitosis to G1, a period of cell growth.

Towards the end of her doctorate, Amon became interested in fruitfly genetics and read the work of Ruth Lehmann, then a faculty member at MIT and a member of the Whitehead Institute. Impressed by the elegance of Lehmann’s genetic approach, she applied and was accepted to her lab. In 1994, Amon arrived in the United States, not knowing that it would become her permanent home or that she would eventually become a professor.

While Amon’s love affair with  fruitfly genetics would prove short, her promise was immediately apparent to Lehmann, now director of the Whitehead Institute. “I will never forget picking Angelika up from the airport when she was flying in from Vienna to join my lab. Despite the long trip, she was just so full of energy, ready to talk science,” says Lehmann. “She had read all the papers in the new field and cut through the results to hit equally on the main points.”

But as Amon frequently was fond of saying, “yeast will spoil you.” Lehmann explains that “because they grow so fast and there are so many tools, ‘your brain is the only limitation.’ I tried to convince her of the beauty and advantages of my slower-growing favorite organism. But in the end, yeast won and Angelika went on to establish a remarkable body of work, starting with her many contributions to how cells divide and more recently to discover a cellular aneuploidy program.”

In 1996, after Lehmann had left for New York University’s Skirball Institute, Amon was invited to become a Whitehead Fellow, a prestigious program that offers recent PhDs resources and mentorship to undertake their own investigations. Her work on the question of how yeast cells progress through the cell cycle and partition their chromosomes would be instrumental in establishing her as one of the world’s leading geneticists. While at Whitehead, her lab made key findings centered around the role of an enzyme called Cdc14 in prompting cells to exit mitosis, including that the enzyme is sequestered in a cellular compartment called the nucleolus and must be released before the cell can exit.

“I was one of those blessed to share with her a ‘eureka moment,’ as she would call it,” says Rosella Visintin, a postdoc in Amon’s lab at the time of the discovery and now an assistant professor at the European School of Molecular Medicine in Milan. “She had so many. Most of us are lucky to get just one, and I was one of the lucky ones. I’ll never forget her smile and scream — neither will the entire Whitehead Institute — when she saw for the first time Cdc14 localization: ‘You did it, you did it, you figured it out!’ Passion, excitement, joy — everything was in that scream.”

In 1999, Amon’s work as a Whitehead Fellow earned her a faculty position in the MIT Department of Biology and the MIT Center for Cancer Research, the predecessor to the Koch Institute. A full professor since 2007, she also became the Kathleen and Curtis Marble Professor in Cancer Research, associate director of the Paul F. Glenn Center for Biology of Aging Research at MIT, a member of the Ludwig Center for Molecular Oncology at MIT, and an investigator of the Howard Hughes Medical Institute.

Her pathbreaking research was recognized by several awards and honors, including the 2003 National Science Foundation Alan T. Waterman Award, the 2007 Paul Marks Prize for Cancer Research, the 2008 National Academy of Sciences (NAS) Award in Molecular Biology, and the 2013 Ernst Jung Prize for Medicine. In 2019, she won the Breakthrough Prize in Life Sciences and the Vilcek Prize in Biomedical Science, and was named to the Carnegie Corporation of New York’s annual list of Great Immigrants, Great Americans. This year, she was given the Human Frontier Science Program Nakasone Award. She was also a member of the NAS and the American Academy of Arts and Sciences.

Lighting the way forward

Amon’s perseverance, deep curiosity, and enthusiasm for discovery served her well in her roles as teacher, mentor, and colleague. She has worked with many labs across the world and developed a deep network of scientific collaboration and friendships. She was a sought-after speaker for seminars and the many conferences she attended. In over 20 years as a professor at MIT, she has mentored more than 80 postdocs, graduate students, and undergraduates, and received the School of Science’s undergraduate teaching prize.

“Angelika was an amazing, energetic, passionate, and creative scientist, an outstanding mentor to many, and an excellent teacher,” says Alan Grossman, the Praecis Professor of Biology and head of MIT’s Department of Biology. “Her impact and legacy will live on and be perpetuated by all those she touched.”

“Angelika existed in a league of her own,” explains Kristin Knouse, one of Amon’s former graduate students and a current Whitehead Fellow. “She had the energy and excitement of someone who picked up a pipette for the first time, but the brilliance and wisdom of someone who had been doing it for decades. Her infectious energy and brilliant mind were matched by a boundless heart and tenacious grit. She could glance at any data and immediately deliver a sharp insight that would never have crossed any other mind. Her positive attributes were infectious, and any interaction with her, no matter how transient, assuredly left you feeling better about yourself and your science.”

Taking great delight in helping young scientists find their own “eureka moments,” Amon was a fearless advocate for science and the rights of women and minorities and inspired others to fight as well. She was not afraid to speak out in support of the research and causes she believed strongly in. She was a role model for young female scientists and spent countless hours mentoring and guiding them in a male-dominated field. While she graciously accepted awards for women in science, including the Vanderbilt Prize and the Women in Cell Biology Senior Award, she questioned the value of prizes focused on women as women, rather than on their scientific contributions.

“Angelika Amon was an inspiring leader,” notes Lehmann, “not only by her trailblazing science but also by her fearlessness to call out sexism and other -isms in our community. Her captivating laugh and unwavering mentorship and guidance will be missed by students and faculty alike. MIT and the science community have lost an exemplary leader, mentor, friend, and mensch.”

Amon’s wide-ranging curiosity led her to consider new ideas beyond her own field. In recent years, she has developed a love for dinosaurs and fossils, and often mentioned that she would like to study terraforming, which she considered essential for a human success to life on other planets.

“It was always amazing to talk with Angelika about science, because her interests were so deep and so broad, her intellect so sharp, and her enthusiasm so infectious,” remembers Vivian Siegel, a lecturer in the Department of Biology and friend since Amon’s postdoctoral days. “Beyond her own work in the lab, she was fascinated by so many things, including dinosaurs — dreaming of taking her daughters on a dig — lichen, and even life on Mars.”

“Angelika was brilliant; she illuminated science and scientists,” says Frank Solomon, professor of biology and member of the Koch Institute. “And she was intense; she warmed the people around her, and expanded what it means to be a friend.”

Amon is survived by her husband Johannes Weis, and her daughters Theresa and Clara Weis, and her three siblings and their families.

Tyler Jacks, founding director of MIT’s Koch Institute, to step down

A search committee chaired by Institute Professor Phillip Sharp will work to identify a new director for the MIT’s pioneering cancer research center.

Bendta Schroeder | Koch Institute
October 26, 2020

The Koch Institute for Integrative Cancer Research at MIT, a National Cancer Institute (NCI)-designated cancer center, has announced that Tyler Jacks will step down from his role as director, pending selection of his successor.

“An exceptionally creative scientist and a leader of great vision, Tyler also has a rare gift for launching and managing large, complex organizations, attracting exceptional talent and inspiring philanthropic support,” says MIT President L. Rafael Reif. “We are profoundly grateful for all the ways he has served MIT, including most recently his leadership on the Research Ramp Up Lightning Committee, which made it possible for MIT’s research enterprise to resume in safe ways after the initial Covid shutdown. I offer warmest admiration and best wishes as Tyler steps down from leading the Koch and returns full time to the excitement of the lab.”

Jacks, the David H. Koch Professor of Biology, has served as director for more than 19 years, first for the MIT Center for Cancer Research (CCR) and then for its successor, the Koch Institute. The CCR was founded by Nobel laureate Salvador Luria in 1974, shortly after the federal government declared “war on cancer,” with the mission of unravelling the molecular core of cancer. Jacks became the center’s fourth director in 2001, following Luria, Nobel laureate and Institute Professor Phillip Sharp, and Daniel K. Ludwig Professor for Cancer Research Richard Hynes.

Aided by the championship of then-MIT President Susan Hockfield and a gift of $100 million from MIT alumnus David H. Koch ’62, SM ’63, Jacks oversaw the evolution of the Center for Cancer Research into the Koch Institute in 2007 as well as the construction of a new home in Building 76, completed in 2010. The Koch Institute expands the mission of its predecessor by bringing life scientists and engineers together to advance understanding of the basic biology of cancer, and to develop new tools to better diagnose, monitor, and treat the disease.

Under the direction of Jacks, the institute has become an engine of collaborative cancer research at MIT. “Tyler’s vision and execution of a convergent cancer research program has propelled the Koch Institute to the forefront of discovery,” notes Maria Zuber, MIT’s vice president for research.

Bolstered by the Koch Institute’s associate directors Jacqueline Lees, Matthew Vander Heiden, Darrell Irvine, and Dane Wittrup, Jacks oversaw four successful renewals of the coveted NCI-designated cancer center stature, with the last two renewals garnering perfect scores. In 2015, Jacks was the recipient of the James R. Killian Jr. Faculty Achievement Award, the highest honor the MIT faculty can bestow upon one of its members, for his leadership in cancer research and for his role in establishing the Koch Institute.

“Tyler Jacks turned the compelling idea to accelerate progress against cancer by bringing together fundamental biology, engineering know-how, and clinical expertise, into the intensively collaborative environment that is now the Koch Institute for Integrative Cancer Research,” says Hockfield. “His extraordinary leadership has amplified the original idea into a paradigm-changing approach to cancer, which now serves as a model for research centers around the world.”

To support cross-disciplinary research in high-impact areas and expedite translation from the bench to the clinic, Jacks and his colleagues shepherded the creation of numerous centers and programs, among them the Ludwig Center for Molecular Oncology, the Marble Center for Cancer Nanomedicine, the MIT Center for Precision Cancer Medicine, the Swanson Biotechnology Center, the Lustgarten Lab for Pancreatic Cancer Research, and the MIT Stem Cell Initiative. In addition, Jacks has co-led the Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center that brings bioengineers, cancer scientists, and clinical oncologists together to solve some of the most challenging problems in cancer research. Jacks has raised nearly $375 million in support of these efforts, as well as the building of the Koch Institute facility, the Koch Institute Frontier Research Program, and other activities.

Jacks first became interested in cancer as a Harvard University undergraduate while attending a lecture by Robert Weinberg, the Daniel K. Ludwig Professor of Cancer Research and member of the Whitehead Institute, who is himself a pioneer in cancer genetics. After earning his PhD at the University of California at San Francisco under the direction of Nobel laureate Harold Varmus, Jacks joined Weinberg’s lab as a postdoctoral fellow. He joined the MIT faculty in 1992 with appointments in the Center for Cancer Research and the Department of Biology.

Jacks is widely considered a leader in the development of engineered mouse models of human cancers, and has pioneered the use of gene-targeting technology to construct mouse models and to study cancer-associated genes in mice. Strains of mice developed in his lab are used by researchers around the world, as well as by neighboring labs within the Koch Institute. Because these models closely resemble human forms of the disease, they have allowed researchers to track how tumors progress and to test new ways to detect and treat cancer. In more recent research, Jacks has been using mouse models to investigate how immune and tumor cells interact during cancer development and how tumors successfully evade immune recognition. This research is expected to lead to new immune-based therapies for human cancer.

Outside his research and MIT leadership, Jacks co-chaired the Blue Ribbon Panel for the National Cancer Moonshot Initiative, chaired the National Cancer Advisory Board of the National Cancer Institute, and is a past president of the American Association for Cancer Research. He is an elected member of the National Academy of Science, the National Academy of Medicine and the American Academy of Arts and Sciences. Jacks serves on the Board of Directors of Amgen and Thermo Fisher Scientific. He is also a co-founder of T2 Biosystems and Dragonfly Therapeutics, serves as an advisor to several other companies, and is a member of the Harvard Board of Overseers.

Sharp will lead the search for the next director of the Koch Institute, with guidance from noted leaders in MIT’s cancer research community, including Hockfield and Hynes, as well as Angela M. Belcher, head of the Department of Biological Engineering and Jason Mason Crafts Professor; Paula T. Hammond, head of the Department of Chemical Engineering and David H. Koch Professor of Engineering; Amy Keating, professor of biology; Robert S. Langer, David H. Koch Institute Professor; and David M. Sabatini, Professor of Biology and member, Whitehead Institute for Biomedical Research.

“Jacks is a renowned scientist whose personal research has changed the prevention and treatment of cancer,” says Sharp. “His contributions to the creation of the Koch Institute for Integrative Cancer Research and his leadership as its inaugural director have also transformed cancer research at MIT and nationally. By integrating engineers and cancer biologists into a community that shares knowledge and skills, and collaborates with clinical scientists and the private sector, this convergent institute represents the future of biological research in the MIT style.”

After Jacks steps down, he will continue his research in the areas of cancer genetics and immune-oncology and his teaching, while also stewarding the Bridge Project into its second decade.

“It has been a privilege for me to serve as director of the MIT Center for Cancer Research and the Koch Institute for the past two decades and to work alongside many of the brightest minds in cancer research,” says Jacks. “The Koch Institute is a powerhouse of research and innovation, and I look forward to the next generation of leadership in this very special place.”

Cancer researchers collaborate, target DNA damage repair pathways for cancer therapy

MIT researchers find blocking the expressions of the genes XPA and MK2 enhances the tumor-shrinking effects of platinum-based chemotherapies in p53-mutated cancers.

Koch Institute
October 2, 2020

Cancer therapies that target specific molecular defects arising from mutations in tumor cells are currently the focus of much anticancer drug development. However, due to the absence of good targets and to the genetic variation in tumors, platinum-based chemotherapies are still the mainstay in the treatment of many cancers, including those that have a mutated version of the tumor suppressor gene p53. P53 is mutated in a majority of cancers, which enables tumor cells to develop resistance to platinum-based chemotherapies. But these defects can still be exploited to selectively target tumor cells by targeting a second gene to take down the tumor cell, leveraging a phenomenon known as synthetic lethality.

Focused on understanding and targeting cell signaling in cancer, the laboratory of Michael Yaffe, the David H. Koch Professor Science and director of the MIT Center for Precision Cancer Medicine, seeks to identify pathways that are synthetic lethal with each other, and to develop therapeutic strategies that capitalize on that relationship. His group has already identified MK2 as a key signaling pathway in cancer and a partner to p53 in a synthetic lethal combination.

Now, working with a team of fellow researchers at MIT’s Koch Institute for Integrative Cancer Research, Yaffe’s lab added a new target, the gene XPA, to the combination. Appearing in Nature Communications, the work demonstrates the potential of “augmented synthetic lethality,” where depletion of a third gene product enhances a combination of targets already known to show synthetic lethality. Their work not only demonstrates the effectiveness of teaming up cancer targets, but also of the collaborative teamwork for which the Koch Institute is known.

P53 serves two functions: first, to give cells time to repair DNA damage by pausing cell division, and second, to induce cell death if DNA damage is too severe. Platinum-based chemotherapies work by inducing enough DNA damage to initiate the cell’s self-destruct mechanism. In their previous work, the Yaffe lab found that when cancer cells lose p53, they can re-wire their signaling circuitry to recruit MK2 as a backup pathway. However, MK2 only restores the ability to orchestrate DNA damage repair, but not to initiate cell death.

The Yaffe group reasoned that targeting MK2, which is only recruited when p53 function is absent, would be a unique way to create a synthetic lethality that specifically kills p53-defective tumors, by blocking their ability to coordinate DNA repair after chemotherapy. Indeed, the Yaffe Lab was able to show in pre-clinical models of non-small cell lung cancer tumors with mutations in p53, that silencing MK2 in combination with chemotherapy treatment caused the tumors to shrink significantly.

Although promising, MK2 has proven difficult to drug. Attempts to create target-specific, clinically viable small-molecule MK2 inhibitors have so far been unsuccessful. Researchers led by co-lead author Yi Wen Kong, then a postdoc in the Yaffe lab, have been exploring the use of RNA interference (siRNA) to stop expression of the MK2 gene, but siRNA’s tendency to degrade rapidly in the body presents new challenges.

Enter the potential of nanomaterials, and a team of nanotechnology experts in the laboratory of Paula Hammond, the David H. Koch Professor of Engineering, head of the MIT Department of Chemical Engineering, and the Yaffe group’s upstairs neighbor. There, Kong found a willing collaborator in then-postdoc Erik Dreaden, whose team had developed a delivery vehicle known as a nanoplex to protect siRNA until it gets to a cancer cell. In studies of non-small cell lung cancer models where mice were given the MK2-targeting nanocomplexes and standard chemotherapy, the combination clearly enhanced tumor cell response to chemotherapy. However, the overall increase in survival was significant, but relatively modest.

Meanwhile, Kong had identified XPA, a key protein involved in another DNA repair pathway called NER, as a potential addition to the MK2-p53 synthetic lethal combination. As with MK2, efforts to target XPA using traditional small-molecule drugs have not yet proven successful, and RNA interference emerged as the team’s tool of choice. The flexible and highly controllable nature of the Hammond group’s nanomaterials assembly technologies allowed Dreaden to incorporate siRNAs against both XPA and MK2 into the nanocomplexes.

Kong and Dreaden tested these dual-targeted nanocomplexes against established tumors in an immunocompetent, aggressive lung cancer model developed in collaboration between the laboratories of professor of biology Michael Hemann and Koch Institute Director Tyler Jacks. They let the tumors grow even larger before treatment than they had in their previous study, thus raising the bar for therapeutic intervention.

Tumors in mice treated with the dual-targeted nanocomplexes and chemotherapy were reduced by up to 20-fold over chemotherapy alone, and similarly improved over single-target nanocomplexes and chemotherapy. Mice treated with this regimen survived three times longer than with chemotherapy alone, and much longer than mice receiving nanocomplexes targeting MK2 or XPA alone.

Overall, these data demonstrate that identification and therapeutic targeting of augmented synthetic lethal relationships — in this case between p53, MK2 and XPA — can produce a safe and highly effective cancer therapy by re-wiring multiple DNA damage response pathways, the systemic inhibition of which may otherwise be toxic.

The nanocomplexes are modular and can be adapted to carry other siRNA combinations or for use against other cancers in which this augmented synthetic lethality combination is relevant. Beyond application in lung cancer, the researchers — including Kong, who is now a research scientist at the Koch Institute, and Dreaden, who is now an assistant professor at Georgia Tech and Emory School of Medicine — are working to test this strategy for use against ovarian and other cancers.

Additional collaborations and contributions were made to this project by the laboratories of Koch Institute members Stephen Lippard and Omer Yilmaz, the Eisen and Chang Career Development Professor.

This work was supported in part by a Mazumdar-Shaw International Oncology Fellowship, a postdoctoral fellowship from the S. Leslie Misrock (1949) Frontier Fund for Cancer Nanotechnology, and by the Charles and Marjorie Holloway Foundation, the Ovarian Cancer Research Foundation, and the Breast Cancer Alliance.

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.

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.