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Tyler Jacks wins 2020 AACR Princess Takamatsu Memorial Lectureship
American Association for Cancer Research
May 28, 2020

PHILADELPHIA – The American Association for Cancer Research (AACR) is recognizing Tyler Jacks, PhD, Fellow of the AACR Academy, with the 2020 AACR Princess Takamatsu Memorial Lectureship.

Jacks is director of the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), co-director of the Ludwig Center at MIT, and a Howard Hughes Medical Institute Investigator. He is being recognized for transforming cancer research and the development of therapeutic treatments through his remarkable advancement of genetically engineered mouse models and for his seminal discoveries related to oncogenes, tumor suppressor genes, cell death, and immune system regulation of tumor progression.

“Dr. Jacks is a highly esteemed cancer scientist, and we are delighted to recognize his exceptional body of innovative work,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “His groundbreaking research has provided deep insights into cancer initiation and progression and has led to the identification of promising new treatments for cancer patients worldwide. He is revered for his tremendous research achievements as well as for his commitment to collaborative research across the world.  He is richly deserving of this prestigious accolade, which honors the life and work of Princess Takamatsu.”

The AACR Princess Takamatsu Memorial Lectureship is awarded to a scientist whose novel and significant fundamental scientific work has had or may have a far-reaching impact on the detection, diagnosis, treatment, or prevention of cancer, and who embodies the dedication of the Princess to outstanding cancer research and advances that emanate from multinational collaborations. Her Imperial Highness Princess Kikuko Takamatsu was personally instrumental in promoting progress against cancer.  She became a champion of these causes following her mother’s death from bowel cancer in 1933 at the young age of 43.

Jacks is a world-renowned researcher whose career has focused on understanding the genetic events that drive the development of cancer by applying the most advanced techniques of genetic engineering to develop mouse models of disease. He and researchers in his laboratory have engineered mice to carry mutations in many genes known to be involved in human cancer, including tumor suppressor genes such as Rb; oncogenes such as K-Ras; and genes involved in oxidative stress, DNA damage and repair, and epigenetic control of gene expression. These preclinical models have since enabled researchers to further investigate the fundamental initiation and progression mechanisms of colon, lung, pancreatic, and ovarian cancers as well as astrocytomas, peripheral nervous system tumors, retinoblastoma, and soft tissue sarcomas. Furthermore, these mice have been used as essential tools for the testing of novel approaches to cancer prevention, early detection, interception, and treatment. Recently, Jacks has used new genetic engineering techniques to study additional cancer processes, including metastasis and tumor-immune cell interactions.

An active AACR member since 1994, Jacks was elected to the inaugural class of Fellows of the AACR Academy in 2013, served as AACR President from 2009 to 2010, served as a member of the AACR Board of Directors from 2001 to 2004, and is a Trustee Emeritus of the AACR Foundation. Jacks has further served the AACR as chair of the AACR Membership Development Task Force and a member of the AACR Academy Steering Committee; Science Policy and Government Affairs Committee; Cancer Prevention, Early Detection, and Interception Committee; the AACR Team Science Award Committee; and the AACR Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research Committee. Jacks was honored with the AACR Award for Outstanding Achievement in Cancer Research in 1997.

Jacks’ scientific accomplishments have been recognized with numerous honors throughout his career, including the MIT James R. Killian Jr. Faculty Achievement Award (2015), Sergio Lombroso Award in Cancer Research (2015), the Simon M. Shubitz Award (2005), the Paul Marks Prize for Cancer Research (2005), the Chestnut Hill Award for Excellence in Cancer Research (2002), and the Amgen Award (1998). In addition, Jacks is an elected Fellow of the American Academy of Arts and Sciences, member of the National Academy of Sciences, and member of the National Academy of Medicine.

Jacks received his undergraduate degree in Biology from Harvard University and completed his doctorate in Biochemistry under the tutelage of Nobel Laureate Harold Varmus at the University of California, San Francisco.

Cellular players get their moment in the limelight
Greta Friar | Whitehead Institute
May 27, 2020

In order to understand our biology, researchers need to investigate not only what cells are doing, but also more specifically what is happening inside of cells at the level of organelles, the specialized structures that perform unique tasks to keep the cell functioning. However, most methods for analysis take place at the level of the whole cell. Because a specific organelle might make up only a fraction of an already microscopic cell’s contents, “background noise” from other cellular components can drown out useful information about the organelle being studied, such as changes in the organelle’s protein or metabolite levels in response to different conditions.

Whitehead Institute Member David Sabatini and Walter Chen, a former graduate student in Sabatini’s lab and now a pediatrics resident at Boston Children’s Hospital and Boston Medical Center and a postdoctoral researcher at Harvard Medical School, developed in recent years a method for isolating organelles for analysis that outstrips previous methods in its ability to purify organelles both rapidly and specifically. They first applied the method to mitochondria, the energy-generating organelles known as the “powerhouses of the cell,” and published their study in Cell in 2016. Subsequently, former Sabatini lab postdoctoral researcher Monther Abu-Remaileh and graduate student Gregory Wyant applied the method to lysosomes, the recycling plants of cells that break down cell parts for reuse, as described in the journal Science in 2017. In collaboration with former Sabatini lab postdoctoral researcher Kivanc Birsoy, Sabatini and Chen next developed a way to use the mitochondrial method in mice, as described in PNAS in 2019. Now, in a paper published in iScience on May 22, Sabatini, Chen, and graduate student Jordan Ray have extended the method for use on peroxisomes, organelles that play essential roles in human physiology.

“It’s gratifying to see this toolkit expand so we can use it to gain insight into the nuances of these organelles’ biology,” Sabatini says.

Using their organellar immunoprecipitation techniques, the researchers have uncovered previously unknown aspects of mitochondrial biology, including changes in metabolites during diverse states of mitochondrial function. They also uncovered new aspects of lysosomal biology, including how nutrient starvation affects the exchange of amino netbet sports bettingacids between the organelle and the rest of the cell. Their methods could help researchers gain new insights into diseases in which mitochondria or lysosomes are affected, such as mitochondrial respiratory chain disorders, lysosomal storage diseases, and Parkinson’s Disease. Now that Sabatini, Chen, and Ray have extended the method to peroxisomes, it could also be used to learn more about peroxisome-linked disorders.

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The researchers’ method is based on “organellar immunoprecipitation,” which utilizes antibodies, immune system proteins that recognize specific perceived threats that they are supposed to bind to and help remove from the body. The researchers create a custom tag for each type of organelle by taking an epitope, the section of a typical perceived threat that antibodies recognize and bind to, and fusing it to a protein that is known to localize to the membrane of the organelle of interest, so the tag will attach to the organelle. The cells containing these tagged organelles are first broken up to release all of the cell’s contents, and then put in solution with tiny magnetic beads covered in the aforementioned antibodies. The antibodies on the beads latch onto the tagged organelles. A magnet is then used to collect all of the beads and separate the bound organelles from the rest of the cellular material, while contaminants are washed away. The resulting isolated organelles can subsequently be analyzed using a variety of methods that look at the organelles’ metabolites, lipids, and proteins.

With their method, Chen and Sabatini have developed an organellar isolation technique that is both rapid and specific, qualities that prior methods have typically lacked. The workflow that Chen and Sabatini developed is fast—this new iteration for peroxisomes takes only 10 minutes to isolate the tagged organelles once they have been released from cells. Speed is important because the natural profile of the organelles’ metabolites and proteins begins to change once they are released from the cell, and the longer the process takes, the less the results will reflect the organelle’s native state.

“We’re interested in studying the metabolic contents of organelles, which can be labile over the course of an isolation,” Chen says. “Because of their speed and specificity, these methods allow us to not only better assess the original metabolic profile of a specific organelle but also study proteins that may have more transient interactions with the organelle, which is very exciting.”

PEROXISOMES TAKE THE LIMELIGHT

Peroxisomes are organelles that are important for multiple metabolic processes and contribute to a number of essential biological functions, such as producing the insulating myelin sheaths for neurons. Defects in peroxisomal function are found in various genetic disorders in children and have been implicated in neurodegenerative diseases as well. However, compared to other organelles such as mitochondria, peroxisomes are relatively understudied. Being able to get a close-up look at the contents of peroxisomes may provide insights into important and previously unappreciated biology. Importantly, in contrast to traditional ways of isolating peroxisomes, the new method that Sabatini, Chen, and Ray have developed is not only fast and specific, but also reproducible and easy to use.

“Peroxisomal biology is quite fascinating, and there are a lot of outstanding questions about how they are formed, how they mature, and what their role is in disease that hopefully this tool can help elucidate,” Ray says.

An exciting next step may be to adapt the peroxisome isolation method so it can be used in a mammaliam model organism, such as mice, something the researchers have already done with the mitochondrial version.

“Using this method in animals could be especially helpful for studying peroxisomes because peroxisomes participate in a variety of functions that are essential on an organismal rather than cellular level,” Chen says. Going forward, Chen is interested in using the method to profile the contents of peroxisomes in specific cell types across a panel of different mammalian organs.

While Chen sets out to discover what unknown biology the peroxisome isolation method can reveal, researchers in Sabatini’s lab are busy working on another project: extending the method to even more organelles.

Written by Greta Friar

***

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

***

Citations:

G. Jordan Ray, Elizabeth A. Boydston, Emily Shortt, Gregory A. Wyant, Sebastian Lourido, Walter W. Chen, David M. Sabatini,  “A PEROXO-Tag Enables Rapid Isolation of Peroxisomes from Human Cells,” iScience, May 22, 2020.

Bayraktar et al., “MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo,” PNAS, Jan 2, 2019.

Abu-Remaileh et al., “Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes,” Science, Nov 10, 2017.

Chen et al., “Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism,” Cell, August 25, 2016.

Six from MIT awarded research funding to address Covid-19

Multi-institutional MassCPR initiative announces more than $16.5 million to support 62 Boston-area projects.

Mindy Blodgett | Institute for Medical Engineering and Science
May 22, 2020

As the world grapples with the continuing challenges of the Covid-19 pandemic, a multi-institutional initiative has been formed to support a broad range of research aimed at addressing the devastation to global public health, including projects by six MIT faculty.

Called the Massachusetts Consortium on Pathogen Readiness (MassCPR), and based at Harvard Medical School (HMS), it was conceived to both battle the myriad effects of SARS-CoV-2 and prepare for future health crises. Now, MassCPR has announced more than $16.5 million in funding to support 62 research projects, all with the potential for significant impact in fighting the pandemic on several fronts.

MassCPR includes scientists and clinicians from Harvard, MIT, Boston University, Tufts University, and the University of Massachusetts, as well as local biomedical research institutes, biotech companies and academic medical centers. The projects selected in the initial round of funding were based on the MassCPR’s primary scientific and clinical focus areas: the development of vaccines, therapies and diagnostic tools, clinical management, epidemiology and understanding how SARS-CoV-2 causes disease.

Of the projects selected, six are led by MIT faculty:

Lee Gehrke, the Hermann von Helmholtz Professor of Health Sciences and Technology, MIT Institute for Medical Engineering and Science (IMES), a professor at HMS and a member of the faculty at the Harvard-MIT Health Sciences and Technology program (HST), will receive funding for work to develop a “simple and direct antigen rapid test for SARS-CoV-2 infections.” A Cambridge-based startup, E25Bio, which is using technology developed by Gerhke, has been working on a paper-based test that can deliver results in under half an hour. Gehrke, the CTO of E25Bio, says that the funding will help to accelerate the final stages of producing and introducing this test into patient care. “We have been working on diagnostic tests overall for over 10 years,” Gehrke says. “We started working on a Covid test as soon as the news came of potential danger back in January.” Gehrke says that the test is “manufacturing-ready” and that they have conducted small-scale manufacturing runs with a local Massachusetts-based company that will be able to scale up once clinical tests are complete. E25Bio has submitted the test to the FDA for emergency use authorization.

Angela Belcher, head of the Department of Biological Engineering, the James Mason Crafts Professor of Biological Engineering and Materials Science and Engineering, and a member of the Marble Center for Cancer Nanomedicine at the Koch Institute for Integrative Cancer Research, will also receive support for her research proposal, “Novel nanocarbon materials for life-development of distributable textiles that filtrate/neutralize dangerous viruses/bacteria to protect medical professional and civilians from virus pandemic disease.”

Jianzhu Chen, a professor in the Department of Biology, also a member of the Koch Institute and a co-director of the Center for Infection and Immunity at the Chinese Academy of Sciences, was selected for a project focusing on “enhancing mRNA-based coronavirus vaccines with lymph node-targeted delivery and neutralizing antibody-inducing adjuvant.” Chen says that the grant will help fund proposed research aimed at devising an effective vaccine, and that the money will “help us to jumpstart our research on SARS-CoV-2,” as well as vaccines to address other pathogens.

Bruce Walker, professor of the practice at IMES and the Department of Biology, founding director of the Ragon Institute of MGH, MIT, and Harvard, and Phillip T and Susan netbet sports betting appM Ragon Professor of Medicine at Harvard Medical School, will receive support for research on “A highly networked, exosome-based SARS-CoV-2 vaccine.”

Feng Zhang’s project, “Development of a point-of-care diagnostic for COVID-19,” was also selected. Zhang is the James and Patricia Poitras Professor of Neuroscience and a professor of brain and cognitive sciences and biological engineering at MIT, and a core member of the Broad Institute of MIT and Harvard.

Siqi Zheng, the Samuel Tak Lee Associate Professor in the Department of Urban Studies and Planning and faculty director of the Center for Real Estate will receive funding for research on quantifying “the role of social distancing in shaping the Covid-19 curve: incorporating adaptive behavior and preference shifts in epidemiological models using novel big data in 344 Chinese cities.” Zheng calls the funding “crucial” in research that will compare different regions and how people react to social and physical distancing during a pandemic, and will examine various government policies aimed at controlling the spread of the virus.

Decoding development

Despite being 2,000 miles apart, two researchers are devising deep learning algorithms to predict embryonic tissue folding.

Raleigh McElvery
May 18, 2020

Since March when MIT’s new COVID-19 policies took effect, the research labs on campus have been vacant, save a skeleton crew of essential workers. Despite being separated from their benches, microscopes, and pipets, biologists have devised creative solutions to continue working remotely. In one lab, a postdoc and an undergraduate are using their time at home to develop a deep learning algorithm to spot hidden clues about embryonic development.

Professor Adam Martin’s lab studies the fruit fly embryo, which consists of a single layer of cells encircling a yolk core about three hours after fertilization. Within the next few minutes, a band of cells on the surface furrows inward, forming a critical fold that helps determine where the cells will go and what roles they will eventually play.

Postdoc Hannah Yevick has spent most of her time in the Martin lab focusing on the protein myosin, which forms a network of connections that links cells together and helps generate the force needed to fold the embryo. With her eye to the microscope, she’s been investigating how this ball of cells compensates for damage and continues to fold correctly despite occasional disruptions to the myosin network. But it remains unclear how cells coordinate to overcome such impediments, and what factors besides myosin aid the process. Yevick began to wonder if there was a way to extract hidden clues from her microscope pictures that would predict which embryos would develop properly and which would not.

Deep learning, a type of machine learning, has become a popular tool to detect and classify visual data. Just like the brain, deep learning algorithms run on sets of interconnecting nodes that can be trained to distinguish features and predict outcomes. (For example, differentiating a cat from a dog, or recognizing a friend in a Facebook picture.) Before an algorithm can complete these tasks on its own, however, researchers must train it using a set of practice images. Some scientists are training algorithms intended for use in clinical settings, from AI-based chatbots to diagnostic assistance that helps predict whether a patient has cancer.

Man in shirt and tie
Prateek Kalakuntla, a third-year Course 20 major and Course 6 minor.

“Deep learning shows great promise in clinical settings,” Yevick says, “and that got me thinking about ways to bring it back into the lab, and dig deeper into fundamental questions about development.”

Although she conducts computational analyses to decipher her microscopy images of fly embryos, Yevick hadn’t considered leveraging deep learning algorithms to predict developmental outcomes until a few months ago. In fact, she’d never tried any machine learning techniques at all. Sitting at home sans microscope during a pandemic seemed like the perfect time to start.

Right before the Martin lab dispersed per MIT’s COVID-19 policies, Yevick gained a collaborator: undergraduate researcher Prateek Kalakuntla, a third-year Course 20 (Biological Engineering) major with a minor in Course 6 (Electrical Engineering and Computer Science). He returned to his home in Dallas, Texas while Yevick remained in Cambridge.

“I was looking for a new project, and this seemed like the perfect one to start from home,” Kalakuntla says. “Our experience of practical machine learning is limited, so we assign ourselves research to do individually, and then check in with each other regularly.”

Despite nearly 2,000 miles separating them, the duo meets via Zoom once or twice a week to discuss their progress. They have been taking online tutorials in deep learning, provided by MIT OpenCourseWare, and gleaning information from scientific papers and colleagues.

“When you’re learning new things, it’s fun to have someone else to bounce ideas off,” Yevick says. “We’re exploring machine learning and gaining basic skills that will help us shape and address important questions moving forward.”

Two people at computer
Adam Martin and Hannah Yevick examine a video of a folding embryo.

At the moment, they’re practicing by constructing codes pulled from online exercises. Eventually, they aim to create and train their own algorithm and feed it images of embryos, taken just a few minutes into the stage of development where the layer of cells begins to furrow inward. The algorithm will then predict whether or not the embryo will develop correctly over the course of the 15-minute folding process.

Yevick and Kalakuntla intend to collect images from the entire lab, gathering as much data as possible to teach the algorithm to discern successful folds from failed ones. But they hope the algorithm will eventually teach them a thing or two as well — namely, where and when critical proteins are working to influence development.

“We’re feeding the algorithm entire images, but it’s pulling out what it deems to be the most interesting parts,” Kalakuntla says. “These could be specific regions of tissue or time periods that provide hints about the necessary proteins and cell shapes, which we can then analyze further.”

Although they’ll train their algorithm on images of fruit fly embryos, Kalakuntla hopes their model could eventually be applied to other organisms like mice or frogs — and even predict outcomes for data sets lacking images of later developmental stages.

“Machine learning can give us a birds-eye view of how cells coordinate collective movements, and show us ‘signatures’ that we might not have otherwise considered,” Yevick says. “Working remotely is certainly not ideal, but it’s given us the chance to gain new skills like this.”

Third annual Science Slam becomes first virtual Research Slam

Nine biology alumni had just three minutes and one slide to awe the audience and judges.

Raleigh McElvery | Department of Biology
May 13, 2020

When MIT announced its pandemic polices back in March, all in-person events were canceled, including the Department of Biology’s third annual Science Slam. Instead, the department devised a new plan in tandem with MIT’s Alumni Association: a virtual slam featuring biology alumni. On April 30, roughly 300 attendees gathered via Zoom to hear nine graduates from Course 7 (Biology) and 5-7 (Chemistry and Biology) share their research.

A science slam features a series of short presentations where researchers explain their work in a compelling manner, and — as the name suggests — make an impact. These presentations aren’t just talks; they’re performances geared toward a science-literate but non-specialized public audience. In this case, competitors were each given one slide and three minutes to tell their scientific tales and earn votes from audience members and judges. Viewers could type questions into the Zoom Q&A function in real-time, and after the prizes were awarded the audience split into breakout rooms to connect with the top three finishers.

The judges included Holden Thorp, editor-in-chief of the Science family of journals; Bob Prior, executive editor of the MIT Press; Vivian Siegel, director of communications for the Department of Biology; and Ari Daniel PhD ’08, an independent science reporter who crafts digital videos for PBS NOVA and co-produces the Boston branch of Story Collider.

The nine competitors included alumnae currently working as graduate students, postdocs, and research scientists — as well as the associate director for research at the U.S. Food and Drug Administration (FDA). In order of appearance, they were:

  • Hanna Starobinets ’09, a research scientist at Genocea, who spoke about devising personalized vaccines that train the immune system to fight cancer;
  • Suzanne Epstein PhD ’79, the FDA’s associate director for research, who spoke about targeting conserved viral proteins to formulate universal vaccines that combat all influenza strains;
  • Amy Norovich ’08, a postdoc at Columbia University, who spoke about the ways male and female fish see the world, and how those differences impact behavior;
  • Helen Hou ’10, also a postdoc at Columbia University, who spoke about how our brains distinguish the sounds we generate from the sounds others make, and what happens when disease interferes with this ability;
  • NetBet live casinoMaya Jay, ’18, a graduate student at Harvard Medical School, who spoke about how the chemical dopamine helps the brain encode actions and learn behaviors;
  • Lori Huberman ’07, a project scientist at the University of California at Berkeley, who spoke about developing a high-throughput functional genomics platform to study filamentous fungi;
  • Juhyun Oh ’09, a postdoc at Massachusetts General Hospital, who spoke about designing antibody-based imaging techniques, which allow deep profiling of immune cells in a scalable fashion to treat cancer;
  • Alissandra Hillis ’18, a graduate student at Harvard University, who spoke about using genetic tools to identify combinatorial breast cancer treatments that require lower doses and prevent drug resistance; and
  • Allegra Hawkins ’14, a postdoc at Weill Cornell Medicine, who spoke about mapping tumors in order to understand the location and function of each individual cancer cell.

The event was moderated and co-organized by Joe McGonegal, director of alumni education. Like the Department of Biology, the Alumni Association has been hosting research slams for three years running. “It was a natural collaboration,” McGonegal says. “There were lots of moving parts, and given our lean staffing and remote production, I’m surprised the entire thing didn’t sink for one reason or another. There was plenty of room for improvement for sure, but for a pilot virtual slam I couldn’t have asked for more.”

McGonegal collaborated with Siegel, a judge and co-organizer, to plan the event. “It’s always a great treat to hear members of our biology community share their research in the slam format,” she says. “When Joe approached me about collaborating to hold a virtual slam, I immediately agreed. Hearing from our alumni was inspiring, and I hope we can do it again.”

There were four prizes: three awarded by the judges and another determined by the audience. Jay earned first place from the judges, as well as the honor of crowd favorite, while Hawkins and Oh received second and third places, respectively. The Alumni Association donated a total of $2,000 to MIT’s Covid-19 research funds in their names.

First-place winner Jay says that many scientists make a habit of describing their work in inaccessible terms — but conveying research to a wider audience is a critical skill. “The slam provided a perfect opportunity to share my graduate work with the MIT and alumni communities, while practicing explaining our science and its applications for anyone to understand,” she says. “Condensing complex science into a three-minute spiel is hard, but I appreciated the challenge and am glad the work paid off!”

Aviv Regev to join Genentech in August
Broad Institute
May 11, 2020

After 14 years at the Broad Institute, Aviv Regev will be taking up an extraordinary opportunity to influence biomedicine in August 2020. She has accepted the position of Executive Vice President of Genentech Research and Early Development, one of the most influential roles in the pharmaceutical industry, with the opportunity to make transformative change in therapeutic development. Below, find a note to the Broad community from Eric.

ERIC LANDER’S NOTE:

I’m writing today to share the bittersweet news that, after 14 years at the Broad Institute, Aviv Regev will be taking up an extraordinary opportunity to influence biomedicine. She has accepted the position of Executive Vice President of Genentech Research and Early Development, and a member of the Roche Extended Corporate Executive Committee reporting to the CEO of Roche.

This is one of the most influential roles in the pharmaceutical industry, with the opportunity to make transformative change in therapeutic development.

Aviv will continue at the Broad until August 1, when she will officially assume the role at Genentech. She will continue to travel back and forth to maintain her lab activities at the Broad for another year, until summer 2021. She also plans to have a lab at Genentech.

Aviv was not looking for a new position. She had been clear that there was simply no place in academic science that she would want to be other than the Broad Institute.

The offer to be one of the senior leaders of Roche and Genentech came as a surprise, but it offered the opportunity to do something extraordinary — shape the entire therapeutic portfolio of one of the world’s best biopharma firms.

Aviv’s departure is a great loss for the Broad community, but I am thrilled for her to have this amazing opportunity.

Aviv is a force of nature.

She was the first faculty member recruited after the formation of the Broad Institute, which she joined in 2006 after running a computational biology lab as Fellow at the Bauer Center at Harvard.

Over the next fourteen years, Aviv has had an extraordinary impact on the science in the Broad community — propelling advances in both experimental and computational biology:

  • She pioneered the creation of methods for single-cell biology, making it possible to read out and interpret gene expression in individual cells.
  • Starting with an initial paper reporting single-cell RNA sequencing of 18 cells, she has led a revolution that has touched every area of biology at Broad and around the world.
  • At the Broad, she founded the Klarman Cell Observatory, which has become the leading nexus for creativity advances in the methodology and application of cell circuits, single-cell biology, and tissue biology.
  • In parallel, she has taken on the analytical challenge of extracting deep biological insights from the massive amounts of data generated by single-cell biology — drawing on the frontiers of data science and machine learning.
  • She amplified the impact through her work to form the Human Cell Atlas, an international collaboration to understand all cell types in the human body that now involves more than 1,100 institutions in 71 countries.
  • She has also built strong ties between Broad and Israel, including with the Broad-ISF Partnership.

Aviv has also played a central role in the Broad’s culture of mentorship. She has led a thriving lab, training dozens of postdocs and graduate students who now pursue independent academic careers as leaders in their own areas. As Chair of the Faculty, Aviv has helped to support the extended Broad faculty. In less formal but numerous ways, she has served as a mentor and sounding board for so many people at all levels.

She has also been a member of the Executive Leadership Team, guiding our most important institutional decisions.

Finally, she has been such a tremendous friend and colleague to me.

As hard as it is to contemplate the Broad without her, both Aviv and I know that the Broad community will use the transition as an opportunity to further strengthen our community — with Broadies stepping up to contribute scientific vision and institutional leadership.

Aviv and I are committed to ensuring the long-term success of the activities she has led. In particular, the Klarman Cell Observatory and its remarkable capabilities and community around single-cell and tissue biology will continue as an essential part of the Broad, led by deeply engaged champions. With their leadership, KCO will remain a vibrant and thriving community for many years to come. Aviv will also continue to co-chair the Human Cell Atlas Initiative, and Broad will remain as dedicated as ever to the ambitious international effort.

I am grateful to Aviv for her commitment to ensuring that the Broad only grows stronger and for her eagerness to remain engaged with the Broad community in the months and years ahead.

It’s hard to convey news about transitions in the midst of the pandemic, with many Broadies working round the clock on the scientific response and without the ability to get together.

We will, however, have a chance to celebrate Aviv — either in person or virtually — before August.

For now, I hope you will join me in congratulating Aviv on this new challenge and in thanking her for all that she has done.

Pollen research inspires art
May 10, 2020
Fu-shuang Li, a research scientist in Whitehead Institute Member Jing-Ke Weng’s lab, has collected flowers or ferns from over 160 different species as part of his research into the chemistry of a super-tough molecule in pollen and plant spores that gives them their tough outer shells and helped plants survive their original migration to land. Collecting the flowers often requires careful timing. Many plants bloom for a brief window, and that window is the only time they produce the pollen that Li needs for his research. There’s no way to know exactly when each plant will bloom, other than to observe them, and if Li misses this window for any of the species, he has to wait a whole year for another chance to collect the pollen he needs. Because of this, Li has spent many hours walking the sprawling grounds of the Arnold Arboretum in the Jamaica Plain neighborhood of Boston, one of his main collection sites, to check in on the plants he needs and see if they are ready for collection.

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At the Arnold Arboretum. Photo: Fu-shuang Li/ Whitehead Institute

During his regular visits to observe the plants, Li became taken with the beauty of the flowers and ferns he was collecting, inspiring him to turn some of his research samples into art. In doing so, Li is contributing to a rich tradition of combining science and art—from historical scientific sketches to artistic modern microscopy—and following in the footsteps of other Whitehead scientists. On each collection trip, Li first takes the samples he needs for his research NetBet live casinoand then, with permission from the managers of the sites, he takes a few extra. He presses these extra flowers and ferns to preserve them. Not all 160 species lend themselves to pressing—some are too bulky, or fade and crumble instead of drying nicely. Li has turned the ones that did press well into small laminated cards.

“My favorites are the ferns,” Li says, looking through the collection of cards. “I think they are very beautiful.”

Several other members of Weng’s lab have aided Li in gathering the large number of specimens required for his research. In order to procure samples from all of the species that he needs, the group has collected not only from the Arnold Arboretum of Harvard University, but also from the Botanic Garden of Smith College and the University of Connecticut’s Ecology and Evolutionary Biology Greenhouse. Last year, Li designed baseball caps bearing images of pollen under an electron microscope. He gave one of these hats to Andrew Mitchell, the Weng Lab member who collected the most specimens, second to Li, last spring. This year, he plans to gift some of the flower-art cards to the people who assist him.

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Photo: Conor Gearin/ Whitehead Institute

A tough subject

Li is using the many samples that he and his lab have collected to investigate sporopollenin, an impressively tough molecule that is found in both pollen and spores—small reproductive cells that ferns and other non-pollen bearing plants use to procreate.

“Among organic things, sporopollenin is one of the strongest you can find in nature,” Li says.

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Photo: “Three Species Pollen Grains” by Asja Radja is licensed under CC-BY-4.0

The molecule’s toughness played a key role in plants’ evolutionary history. Plant life began in the ocean, and in order to make the jump to land, plants and their reproductive cells needed to be able to handle the terrestrial world’s harsh conditions, such as exposure to the sun’s UV radiation and drought. Sporopollenin’s chemical structure makes it incredibly durable, unreactive to its environment, and protective against UV; this gave spores, and later pollen, the protection they needed to survive on land. Besides its significance in the origins of terrestrial ecosystems, sporopollenin is an exciting blueprint for nature-inspired design. Li, Weng, and collaborators cracked the chemical structure of sporopollenin a few years ago. Using this information, researchers may be able to create products that mimic sporopollenin’s durability and inertness, for example in medical implants that need to stay intact and unreactive in patients’ bodies.

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Pitch pine. Photo: “Pinus rigida cone Poland” by Crusier is licensed under CC BY 3.0

The researchers first identified the structure of sporopollenin in pitch pine. Now Li is investigating differences in the molecule across plant species, tracing the molecule’s evolution along with that of the plant kingdom—hence the need for his extensive collection trips. Weng and Li are especially interested in finding out how sporopollenin changed with the evolution of flowering plants in order to better understand the differences in pollen characteristics that arose alongside changes in plant structure and modes of pollination.

Pollen endures in nature, and now art

Sporopollenin’s hardiness, and the longevity it gives to pollen and spores, inspired Li’s next art project: pollen rings. Rings symbolize endurance, Li says—their perfect circles can represent eternity, or a life-long commitment to another person. Pollen grains, meanwhile, can stay intact for thousands or even millions of years. Pollen is abundant in fossil records and one of the first pollen rings that Li made contains fossil pollen from the Cretaceous Period, the age of dinosaurs.

“Pollen is special. The morphology survives for millions of years,” Li says. “So I always thought about the meaning of putting it in a ring.”

NetBet sport

Photo: Conor Gearin/ Whitehead Institute

Li has also made rings using pine and lily pollen. Each type of pollen has its own color. The rings made of pine pollen are bright yellow, while the ones made with lily have a slightly purplish hue. Li creates the rings by mixing the pollen with resin and shaping the mixture in a mold. The rings are then hardened under UV light. Li observed a fun display of sporopollenin’s protective qualities during this process. The more pollen he mixed into a ring, the longer that ring would take to harden—he suspects because the sporopollenin absorbs UV. After the rings are hardened, Li sands and polishes them. He is saving the most carefully polished ring as a present for his wife.

Seeking further inspiration

Inspecting flowers at the Arnold Arboretum. Photo: Fu-shuang Li/ Whitehead Institute

As Li plans for his next round of collection trips this spring, he is also looking for his next art project. Unfortunately, due to the coronavirus pandemic, some of Li’s upcoming collection trips have been cancelled, meaning that he may miss his window to catch a few of the plants he needs in bloom. However, the Arnold Arboretum is still accessible, so sometime soon Li will tread the familiar, winding paths through the trees there, checking to see if the few remaining plants he needs for his research have bloomed and waiting for his next spark of inspiration to ignite, starting him on a new artistic endeavor.

Written by Greta Friar

Kerry Emanuel, David Sabatini, and Peter Shor receive BBVA Frontiers of Knowledge awards

Laureates recognized for contributions to climate change, biomedicine, and quantum cryptography.

Sandi Miller | Department of Mathematics
May 8, 2020

The BBVA Foundation awarded three MIT professors Frontiers of Knowledge Awards for their work in climate change, biology and biomedicine, and quantum computation. Department of Earth, Atmospheric, and Planetary Sciences Professor Kerry A. Emanuel, Department of Biology Professor David Sabatini, and Department of Mathematics Professor Peter Shor were recognized in the 12th edition of this annual award.

Kerry Emanuel

Emanuel, the Cecil and Ida Green Professor of Atmospheric Science, earned the BBVA’s Climate Change award “for his fundamental contributions to the understanding of tropical cyclones and how they are affected by climate change,” according to the committee’s citation. “By understanding the essential physics of atmospheric convection … he has unraveled the behavior of tropical cyclones — hurricanes and typhoons — as our climate changes.” He was also lauded for “extraordinary effectiveness in communicating the science of climate change to the public and policymakers.”

Emanuel is the co-founder (with Daniel H. Rothman) and co-director of the MIT Lorenz Center, a climate think tank that fosters creative approaches to learning how climate works. He was the first to link greater hurricane intensity to climate change-induced warming of sea surface waters.

“It is hard to imagine an area of climate science where one person’s leadership is so incontestable,” says Bjorn Stevens, BBVA Foundation committee chairman and director of the Max Planck Institute for Meteorology.

Hurricanes have long been known as destructive natural events, but the underlying physics of them was still largely unknown. Throughout the 1980s and 1990s, after completing degrees at MIT and later joining the EAPS faculty, Emanuel pinned down the mechanisms behind hurricanes. In his research detailing how warming surface oceans fuel storms and increase the intensity, he called them “massive, natural machines that convert the heat they extract from the ocean into wind energy.”

A changing climate will see more powerful hurricanes. Emanuel warns that this will complicate the already-tough task of making accurate forecasts, and predicts that hurricanes will spread into more regions of the planet.

His models currently predict a 5 percent increase in hurricane intensity (i.e., wind speed) for each 1-degree rise in ocean temperatures. “Three degrees of warming would make hurricanes 15 percent more intense, but their destructive potential would actually triple; in other words, with this 15 percent increase in wind speed, the damage would increase by around 45 percent,” says Emanuel, the author of “Divine Wind: The History and Science of Hurricanes” (Oxford Unviersity Press, 2005) and “What We Know about Climate Change” (MIT Press, 2018).

“Today’s most intense hurricanes may have a wind speed at the surface of 85 meters per second, but by the end of this century, unless we curb greenhouse gas emissions, we could start to see speeds of up to 90-92 meters per second. A hurricane’s destructive potential is determined by its wind speed, so in fact, the destructiveness of these storms for human populations would be considerably greater.”

Emanuel says that the international community “is not doing nearly enough” to combat climate change. “We need to stop listening to the voices of denial, and instead listen to our own children, who are crying out for us to act.”

David Sabatini

Sabatini, an MIT professor of biology and member of the Whitehead Institute for Biomedical Research and the Koch Institute for Integrative Cancer Research, shares his Frontiers of Knowledge Award in Biology and Biomedicine with Michael Hall of the University of Basel, for the discovery of a protein kinase that regulates cellular metabolism and growth.

Their discovery of mTOR is used in the study of a wide array of health netbet online sports bettingconditions, including obesity, aging, cancer, diabetes, epilepsy, Alzheimer’s, and Parkinson’s. “Research has suggested that 60 percent of cancers have some mechanism for turning on the mTOR pathway,” Sabatini says. “I could never have imagined the implications of that first discovery.”

Sabatini began his PhD thesis on understanding the mechanism of action of rapamycin, a natural anti-fungal agent proved to have immunosuppressive and anti-cancer properties. It is used to prevent organ rejection in transplant patients.

The two scientists arrived at their findings independently. Hall discovered the target of rapamycin (TOR) protein in yeast cells in 1993 during his time as a senior investigator; Sabatini isolated it in mammals while still a doctoral student, in 1994, and gave it the name mTOR.

In mammalian cells, mTOR — which stands for “mechanistic target of rapamycin,” an immunosuppressant drug that inhibits cell growth — is the keystone molecule in a pathway that regulates cellular metabolic processes in response to nutrients.

Sabatini explains that “mTOR is a switch that turns on in the presence of nutrients, so the body can build material, and when there are no nutrients available it breaks the material down.” The on/off switch of the mTOR switch controls a cascade of hundreds of molecular signals, many of which are still unknown to science.

“The molecular mechanisms that regulate the growth of organisms and coordinate it with the availability of nutrients were unknown until two decades ago,” said the committee.

After the molecule was isolated in yeast and mammals, both researchers began the task of unraveling its multiple organismal functions. Sabatini’s lab has since identified most of the components of the mTOR pathway and shown how they contribute to the function of cells and organisms. His discoveries have opened avenues for identifying disease vulnerabilities and treatment targets for diverse conditions — notably including key metabolic vulnerabilities in pancreatic and ovarian cancer cells and neurodevelopmental defects. He is currently working to exploit those vulnerabilities as targets for new therapies.

Rapamycin is used as an immunosuppressant to prevent rejection of transplanted organs and as an anti-cancer agent. In the treatment of cardiovascular diseases, it is used as a coating for coronary stents to stop new blockages forming in the bloodstream.

Because mTOR is a nutrient sensor, additional research points to caloric restriction for increasing longevity. TOR was the first known protein that influences longevity in all of the four species that scientists commonly use to study aging: yeast, worms, flies, and mice. “We are just scratching the surface” of possible mTOR applications, he says.  “I don’t know if it will help us live to be 120, but I think it will have beneficial effects on different physiological systems, and I am practically sure that it will ameliorate aspects of aging-related diseases.”

Peter Shor

Shor, the Morss Professor of Applied Mathematics, was recognized in the Basic Sciences category for his role in the development of quantum computation and cryptology. He shares this award with IBM Research’s chemical physicist Charles H. Bennett and University of Montreal computer scientist Gilles Brassard.

The award committee remarked on the leap forward in quantum technologies, an advance that draws heavily on the new laureates’ pioneering contributions. The committee stated that their work “spans multiple disciplines and brings together concepts from mathematics, physics, and computer science. Their ideas are playing a key role in the development of quantum technologies for communication and computation.”

Bennett and Brassard invented quantum cryptography in the 1980s to ensure the physical inviolability of data communications. The importance of this work became apparent 10 years later when Shor discovered that a hypothetical quantum computer would render effectively useless the conventional cryptography systems underpinning the privacy and security of today’s internet communications.

Bennett and Brassard’s BB84 protocol — generally acknowledged as the first practical application of the science of quantum information — underpins the security of all our internet communications and transactions, and is based on the existence of mathematical problems that computers cannot solve. Until, as the citation states, “Shor discovered that quantum computers could factorize integers much faster than any supercomputer, therefore compromising the security of conventional cryptographic schemes.”

Says Brassard, “The importance of our work became much more evident after Shor destroyed everything else.” Shor’s Algorithm is now one of the quantum algorithms that comprise the fast-developing language to be spoken by tomorrow’s quantum computers.

Another of Shor’s contributions is an algorithm used to correct quantum computer errors, “an essential requirement for enabling and scaling quantum computations,” the committee wrote.

Quantum computers are exposed to a large volume of noise, causing numerous errors. “Everyone thought that you couldn’t correct errors on quantum computers,” recalls Shor, “because as soon as you try to measure a quantum system you disturb it. In other words, if you try to measure the error so as to correct it, you disturb it and computation is interrupted. My algorithm showed that you can isolate and fix the error and still preserve the computation.”

Quantum cryptography is one of the most advanced branches of quantum technology, which the laureates view as a long-term prospect. “It will be five or 10 years before a quantum computer can do anything approaching useful,” says Shor. With time, however, he is convinced that these machines will deliver revolutionary applications. For example, in biomedicine, “it takes enormous amounts of computer time to simulate the behavior of molecules,” he says. “But quantum computers could achieve that, and help design new drugs.”

The BBVA Foundation promotes knowledge based on research and artistic and cultural creation, and supports activity on the analysis of emerging issues in five strategic areas: environment, biomedicine and health, economy and society, basic sciences and technology, and culture. The Frontiers of Knowledge Awards, spanning eight prize categories, recognize research and creative work of excellence as embedded in theoretical advances, technological developments, or innovative artistic works and styles, as well as fundamental contributions in addressing key challenges of the 21st century.

Since its launch in 2009, the BBVA also has given awards to MIT’s Susan Solomon for climate change; Marvin Minsky, Adi Shamir, Silvio Micali, Shafi Goldwasser, and Ronald Rivest for information and computer technologies; Stephen Buchwald for basic sciences; Edward Boyden for biology and biomedicine; and Daron Acemoglu for economics.

Study finds ‘volume dial’ for turning neural communication up or down
Picower Institute
May 6, 2020

Neuroscientists at MIT’s Picower Institute for Learning and Memory have found that a protein acts like a volume dial for the release of neurotransmitters, the chemicals that neurons release across connections called synapses to stimulate muscles or communicate with other neurons in brain circuits. The findings help explain how synapses work and could better inform understanding of some neurological disorders.

Working in the model of fruit flies, the team determined that the protein Synaptotagmin 7 (SYT7), which is also found in humans and other mammals, constrains the number and availability of neurotransmitter-containing blobs, called vesicles, for release at the synapse. Neurons deploy vesicles to sites called “active zones” to release them across synapses, a process called “vesicle fusion.”  When the scientists reduced SYT7, they saw much more neurotransmitter release at synapses. When they increased the protein, neurotransmitter release dropped significantly.

“You can think of this as almost like a radio’s volume dial,” said senior author Troy Littleton, Menicon Professor of Neuroscience in MIT’s Departments of Biology and Brain and Cognitive Sciences. “If a neuron wants to send more signal out all it has to do is basically reduce the levels of SYT7 protein that it is making. It’s a very elegant way for neurons to turn up or down the amount of output that they are giving.”

The study’s co-lead authors are Zhuo Guan, a research scientist, and Mónica C. Quiñones-Frías, who successfully defended her doctoral thesis on the work May 4. She noted that by acting as that volume dial, the protein could change the nature of a synapse’s activity in a circuit, a property called “synaptic plasticity.”

“Syt7 regulates neurotransmission in a dose-dependent manner and can act as a switch for short term synaptic plasticity,” Quiñones-Frías said.

Research scientist Yulia Akbergenova is also a co-author of the study published in eLife.

Synaptic surprise

Important as they are, the study’s findings are not ones the team was originally looking for.

For decades, neuroscientists have known that the synaptotagmin netbet online sports bettingprotein family plays key roles in synaptic function. In fact, Littleton’s 1993 doctoral dissertation showed that SYT1 promoted a quick release of neurotransmitters when triggered by an influx of calcium ions. But even with SYT1 disabled, synapses could still release neurotransmitters on a slower timeframe. No one has found what promotes that subsequent slower release, but many scientists had pinned their hopes on it being SYT7.

“That’s been something that the whole field, including my lab, has really been searching for,” Littleton said. “So it was a real surprise when we knocked it out and saw just the opposite of what we expected.”

Mutants and microscopes

To study SYT7 the team focused its experiments on synapses in a well characterized locale: the junction between a fly neuron and muscle. The team not only wanted to see what differences changing the protein’s levels would make in synaptic activity there, but also track how it made those differences.

They changed the amount of SYT7 the neuron could produce by mutating and breeding flies in which the gene was completely eliminated, only one copy could be expressed, or in which the gene was overexpressed, producing more SYT7 than normal. For each of these fly lines they measured the surprising inverse relationship between SYT7 and synaptic transmission.

Also, using a technique the lab invented to visually flag neurotransmitter release every time it happens, they mapped how active individual synapses at the neuron-muscle junction were over time. In flies engineered to produce less SYT7 they saw many more synapses with a high propensity for release than they did in normal flies.

Once they confirmed SYT7’s restrictive role, the natural question was how does SYT7 constrain neurotransmitter release. Synapses are very complex, after all, and crucial aspects of SYT7’s role within that machinery had yet to be characterized.

When they compared synapses in normal flies and those missing SYT7 they didn’t see major differences in anatomy or calcium influx that could explain how SYT7 works to limit release.

They then turned their attention to the cycle in which vesicles release their neurotransmitter cargo and are then sent back into the cell to refill with neurotransmitter before rejoining a pool of vesicles ready for redeployment. Their experiments showed that neurons lacking SYT7 didn’t recycle the vesicles differently but they nevertheless had more vesicles in the readily releasable pool (RRP). Moreover, mutants in which SYT7 was overexpressed substantially limited the vesicles in that pool.

“SYT7 limits release in a dosage-sensitive manner by negatively regulating the number of synaptic vesicles available for fusion and slowing recovery of the RRP following stimulation,” they determined.

The final step was to track down where SYT7 resides in the synaptic machinery. Under the microscope they were able to pin it down in a network of tubes surrounding, but not within the active zones. The vantage point is right where other proteins regulating vesicle trafficking also reside, giving SYT7 a clear opportunity to interact with those proteins to regulate the return of vesicles to the active zones.

Implications for disease and plasticity

Understanding more about SYT7’s role at the synapse in mammals could matter in several ways, Littleton said. Two years ago, researchers showed that the protein is reduced in mice harboring a genetic cause of Alzheimer’s disease. And in February another paper showed that patients with bipolar disorder exhibited lower levels of the protein than people who do not have the disorder. Mice with SYT7 knocked out showed some manic and depressive behaviors.

More fundamentally, Littleton and Quiñones-Frías said, is the flexibility or plasticity it can afford. Because SYT7 regulates neurotransmitter release by slowing down the resupply of releasable vesicles, an increase in its levels can transform a synapse from being the kind that sends out large bursts of signal (and therefore transmits more information) early on and then peters out into one that builds up its signal over time. Such distinctions in release timeframe can make important differences in circuit information processing in the brain.

Although the team was able to identify SYT7’s effect at synapses and show key aspects of how it functions, they still hope to determine the exact mechanism that allows the protein to gate vesicle fusion. That work is ongoing.

The National Institutes of Health and the JPB Foundation provided support for the research.