Author: mantulin

Department of Biology receives funds to support summer students

Generous gift from Michael Gould and Sara Moss provides endowed support for MIT’s Summer Research Program in Biology.

Department of Biology
January 27, 2021

Last month, the Department of Biology received a generous gift from Michael Gould and Sara Moss to support students participating in MIT’s Summer Research Program in Biology (MSRP-Bio). Gould is a philanthropist and the retired chair and CEO of Bloomingdales, and Moss is the vice chair of Estée Lauder Companies. Their gift will supplement the existing Bernard S. and Sophie G. Gould Fund, which the couple initiated in 2015 to honor Gould’s parents. Together, these donations will enable many undergraduate students from outside MIT who are interested in a career in life science to participate in MSRP-Bio each summer. To honor the Gould family’s generosity, MSRP-Bio will be renamed the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology, or BSG-MSRP-Bio.

“We are deeply grateful to Mike and Sara for their commitment to and support for our community,” says department head and Praecis Professor Alan Grossman. “Their willingness to enable opportunities for students will allow many talented individuals to benefit from research experiences here at MIT, and foster the next generation of scientists.”

“Mike Gould and Sara Moss are amazing people,” says Mandana Sassanfar, the Department of Biology’s director of outreach. “They’ve made a generous gift that has enabled MRSP-Bio to give many deserving undergraduates a life-changing summer research experience.”

MSRP-Bio is a 10-week summer program offered to non-MIT undergraduates, which provides access to cutting-edge facilities and supervised research in a fast-paced environment. The program encourages students from groups that are historically underrepresented in science, first-generation college students, students from economically disadvantaged backgrounds, and students with disabilities to attend graduate school and pursue careers in basic research.

Every year, roughly 20 participants are placed in laboratories affiliated with the Department of Biology. In total, nearly 400 students have participated in MSRP-Bio since its establishment in 2003. Nearly 300 have already gone to PhD or MD/PhD programs, and of these, 63 have enrolled at MIT for graduate school and 45 have joined the Department of Biology specifically.

Gould and Moss were inspired to create a fund supporting MSRP-Bio because both of Gould’s parents were MIT alumni devoted to mentorship. Bernard “Bernie” Gould ’32 was a beloved biochemistry professor in the Department of Biology and counseled many biology and pre-med students for 50 years. His wife, Sophia Gould CMP ’48, earned a master’s degree in public health at a time when there were few female graduate students at the Institute, and shared this passion for training students.

“I’ve been inspired by my father, who was a first-generation American, cared enormously about his students, and nurtured their intellectual curiosity and drive,” Michael Gould says. “MSRP-Bio does the same by giving each student the opportunity of a lifetime. My dream is for every department at MIT to create a similar program. It would enrich the Institute immeasurably.”

“This gift will have a tremendous impact on the MSRP-Bio program in the biology department, and comes at a crucial time as issues surrounding diversity, equity, and inclusion remain key priorities for the School of Science and Institute,” says Nergis Mavalvala, dean of MIT’s School of Science.

Since its inauguration in 2015, the Bernard S. and Sophie G. Gould Fund has offered scholarships to 30 MSRP-Bio students — six each year. Every summer, Gould and Moss travel to campus to get to know the current Gould fellows. The duo has been continually impressed by the caliber of students, and decided to provide more support to fund additional fellows and ensure the program’s longevity.

“Mike and Sara have a sustained interest in the well-being and success of the Gould fellows, and take pride in these students’ accomplishments,” Sassanfar says. “The Gould Fellowship stands out because of the open relationship between the Mike and Sara and the fellows, which forges meaningful connections that will last for many years.”

Participating in MSRP-Bio was a “life-changing” experience, says former Gould Fellow Meucci Ilunga. “I genuinely mean that — I can only imagine how different my life would be if I had not had that opportunity.”

Former Gould Fellow Asmita Panthi adds that MSRP-Bio showed her what she was capable of accomplishing, and gave her the confidence to apply to graduate school. “I’m so thankful for this impactful fellowship, which gives students like me — who come from small undergraduate institutions or humble backgrounds — the chance to participate in a rigorous research program.”

Four MIT scientists honored with 2021 National Academy of Sciences awards

Pablo Jarillo-Herrero, Aviv Regev, Susan Solomon, and Feng Zhang are the recipients of distinguished awards for major contributions to science.

Laura Carter | School of Science
January 25, 2021

Four MIT scientists are among the 20 recipients of the 2021 Academy Honors for major contributions to science, the National Academy of Sciences (NAS) announced at its annual meeting. The individuals are recognized for their “extraordinary scientific achievements in a wide range of fields spanning the physical, biological, social, and medical sciences.”

The awards recognize: Pablo Jarillo-Herrero, for contributions to the fields of nanoscience and nanotechnology through his discovery of correlated insulator behavior and unconventional superconductivity in magic-angle graphene superlattices; Aviv Regev, for using interdisciplinary information or techniques to solve a contemporary challenge; Susan Solomon, for contributions to understanding and communicating the causes of ozone depletion and climate change; and Feng Zhang, for pioneering achievements developing CRISPR tools with the potential to diagnose and treat disease.

Pablo Jarillo-Herrero: Award for Scientific Discovery

Pablo Jarillo-Herrero, a Cecil and Ida Green Professor of Physics, is the recipient of the NAS Award for Scientific Discovery for his pioneering developments in nanoscience and nanotechnology, which is presented to scientists in the fields of astronomy, materials science, or physics. His findings expand nanoscience by demonstrating for the first time that orientation can be used to dramatically control nanomaterial properties and to design new nanomaterials. This work lays the groundwork for developing a whole new family of 2D materials and has had a transformative impact on the field and on condensed-matter physics.

The biannual award recognizes “an accomplishment or discovery in basic research, achieved within the previous five years, that is expected to have a significant impact on one or more of the following fields: astronomy, biochemistry, biophysics, chemistry, materials science, or physics.”

In 2018, his research group discovered that by rotating two layers of graphene relative to each other by a magic angle, the bilayer material can be turned from a metal into an electrical insulator or even a superconductor. This discovery has fostered new theoretical and experimental research, inspiring the interest of technologists in nanoelectronics. The result is a new field in condensed-matter physics that has the potential to result in materials that conduct electricity without resistance at room temperature.

Aviv Regev: James Prize in Science and Technology Integration

Aviv Regev, who is a professor of biology, a core member of the Broad Institute of Harvard and MIT, a member of the Koch Institute, and a Howard Hughes Medical Institute investigator has been selected for the inaugural James Prize in Science and Technology Integration, along with Harvard Medical School Professor Allon Kelin, for “their concurrent development of now widely adopted massively parallel single-cell genomics to interrogate the gene expression profiles that define, at the level of individual cells, the distinct cell types in metazoan tissues, their developmental trajectories, and disease states, which integrated tools from molecular biology, engineering, statistics, and computer science.”

The prize recognizes individuals “who are able to adopt or adapt information or techniques from outside their fields” to “solve a major contemporary challenge not addressable from a single disciplinary perspective.”

Regev is credited with forging new ways to unite the disciplines of biology, computational science, and engineering as a pioneer in the field of single-cell biology, including developing some of its core experimental and analysis tools, and their application to discover cell types, states, programs, environmental responses, development, tissue locations, and regulatory circuits, and deploying these to assemble cellular atlases of the human body that illuminate mechanisms of disease with remarkable fidelity.

Susan Solomon: Award for Chemistry in Service to Society

Susan Solomon, the Lee and Geraldine Martin Professor of Environmental Studies in the Department of Earth, Atmospheric and Planetary Sciences who holds a secondary appointment in the Department of Chemistry, is the recipient of the Award for Chemistry in Service to Society for “influential and incisive application of atmospheric chemistry to understand our most critical environmental issues — ozone layer depletion and climate change — and for her effective communication of environmental science to leaders to facilitate policy changes.”

The award is given biannually for “contributions to chemistry, either in fundamental science or its application, that clearly satisfy a societal need.”

Solomon is globally recognized as a leader in atmospheric science, notably for her insights in explaining the cause of the Antarctic ozone “hole.” She and her colleagues have made important contributions to understanding chemistry-climate coupling, including pioneering research on the irreversibility of global warming linked to anthropogenic carbon dioxide emissions, and on the influence of the ozone hole on the climate of the southern hemisphere.

Her work has had an enormous effect on policy and society, including the transition away from ozone-depleting substances and to environmentally benign chemicals. The work set the stage for the Paris Agreement on climate, and she continues to educate policymakers, the public, and the next generation of scientists.

Feng Zhang: Richard Lounsbery Award

Feng Zhang, who is the James and Patricia Poitras Professor of Neuroscience at MIT, an investigator at the McGovern Institute for Brain Research and the Howard Hughes Medical Institute, a professor of brain and cognitive sciences and biological engineering at MIT, and a core member of the Broad Institute of MIT and Harvard, is the recipient of the Richard Lounsbery Award for pioneering CRISPR-mediated genome editing.

The award recognizes “extraordinary scientific achievement in biology and medicine” as well as stimulating research and encouraging reciprocal scientific exchanges between the United States and France.

Zhang continues to lead the field through the discovery of novel CRISPR systems and their development as molecular tools with the potential to diagnose and treat disease, such as disorders affecting the nervous system. His contributions in genome engineering, as well as his earlier work developing optogenetics, are enabling a deeper understanding of behavioral neural circuits and advances in gene therapy for treating disease.

In addition, Zhang has championed the open sharing of the technologies he has developed through extensive resource sharing. The tools from his lab are being used by thousands of scientists around the world to accelerate research in nearly every field of the life sciences. Even as biomedical researchers around the world adopt Zhang’s discoveries and his tools enter the clinic to treat genetic diseases, he continues to innovate and develop new technologies to advance science.

The National Academy of Sciences is a private, nonprofit society of distinguished scholars, established in 1863 by the U.S. Congress. The NAS is charged with providing independent, objective advice to the nation on matters related to science and technology as well as encouraging education and research, recognize outstanding contributions to knowledge, and increasing public understanding in matters of science, engineering, and medicine. Winners received their awards, which include a monetary prize, during a virtual ceremony at the 158th NAS Annual Meeting.

This story is a modified compilation from several National Academy of Sciences press releases.

Understanding antibodies to avoid pandemics

Structural biologist Pamela Björkman shared insights into pandemic viruses as part of the Department of Biology’s IAP seminar series.

Saima Sidik | Department of Biology
January 19, 2021

Last month, the world welcomed the rollout of vaccines that may finally curb the Covid-19 pandemic. Pamela Björkman, the David Baltimore Professor of Biology and Bioengineering at Caltech, wants to understand how antibodies like the ones elicited by these vaccines target the SARS-CoV-2 virus that causes Covid-19. She hopes this understanding will guide treatment strategies and help design vaccines against future pandemics. She shared her lab’s work during the MIT Department of Biology’s Independent Activities Period (IAP) seminar series, Immunity from Principles to Practice, on Jan. 12.

“Pamela is an amazing scientist, a strong advocate for women in science, and has a stellar history of studying the structural biology of virus-antibody interactions,” says Whitehead Institute for Biomedical Research Member Pulin Li, the Eugene Bell Career Development Professor of Tissue Engineering and one of the organizers of this year’s lecture series.

Immunology research often progresses from the lab bench to the clinic quickly, as was the case with Covid-19 vaccines, says Latham Family Career Development Professor of Biology and Whitehead Institute Member Sebastian Lourido, who organized the lecture series with Li. He and Li chose to focus this year’s seminar series on immunity because this field highlights the tie between basic molecular biology, which is a cornerstone of the Department of Biology, and practical applications.

“Pamela’s work is an excellent example of how fundamental discoveries can be intimately tied to real-world applications,” Lourido says.

Björkman’s lab has a long history of studying antibodies, which are protective proteins that the body generates in response to invading pathogens. Björkman focuses on neutralizing antibodies, which bind and jam up the molecular machines that let viruses reproduce in human cells. Last fall, the U.S. Food and Drug Administration (FDA) authorized a combination of two neutralizing antibodies, produced by the pharmaceutical company Regeneron, for emergency use in people with mild to moderate Covid-19. This remains one of the few treatments available for the disease.

Together with Michel Nussenzweig’s lab at The Rockefeller University, Börkman’s lab identified four categories of neutralizing antibodies that prevent a protein that decorates SARS-CoV-2’s surface, called the spike protein, from binding to a human protein called ACE2. Spike acts like the virus’s key, with ACE2 being the lock it has to open to enter human cells. Some of the antibodies that Björkman’s lab characterized bind to the tip of spike so that it can’t fit into ACE2, like sticking a wad of chewing gum on top of the virus’s key. Others block spike proteins from interacting with ACE2 by preventing them from altering their orientations. Understanding the variety of ways that neutralizing antibodies work will let scientists figure out how to combine them into maximally effective treatments.

Björkman isn’t satisfied with just designing treatments for this pandemic, however. “Coronavirus experts say this is going to keep happening,” she says. “We need to be prepared next time.”

To this end, Björkman’s lab has put pieces of spike-like proteins from multiple animal coronaviruses onto nanoparticles and injected them into mice. This made the mice generate antibodies against a mix of pathogens that are poised to jump into humans, suggesting that scientists could use this approach to create vaccines before pandemics occur. Importantly, the nanoparticles still work after they’re freeze-dried, meaning that companies could stockpile them, and that they could be shipped at room temperature.

Björkman’s talk was the second in the Immunity from Principles to Practice series, which was kicked off by Gabriel Victora from The Rockefeller University. Victora discussed how antibodies are produced in structures called germinal centers that are found in lymph nodes and the spleen.

Next in the series is Chris Garcia from Stanford University, who will speak on Jan. 19 about his lab’s work on engineering immune signaling molecules to maximize their potential to elicit therapeutic responses. To round out the series, Yasmine Belkaid from the National Institute of Allergy and Infectious Disease will speak on Jan. 26 about interactions between the gut microbiome and the pathogens we ingest. These talks complement a number of career development seminars that were organized by graduate students Fiona Aguilar, Alex Chan, Chris Giuliano, Alice Herneisen, Jimmy Ly, and Aditya Nair.

Biden taps Eric Lander and Maria Zuber for senior science posts

Lander to take a leave of absence to assume Cabinet-level post; Zuber to co-chair presidential advisory council.

Steve Bradt | MIT News Office
January 19, 2021

President-elect Joseph Biden has selected two MIT faculty leaders — Broad Institute Director Eric Lander and Vice President for Research Maria Zuber — for top science and technology posts in his administration.

Lander has been named Presidential Science Advisor, a position he will assume soon after Biden’s inauguration on Jan. 20. He has also been nominated as director of the Office of Science and Technology Policy (OSTP), a position that requires Senate confirmation.

Biden intends to elevate the Presidential Science Advisor, for the first time in history, to be a member of his Cabinet.

Zuber has been named co-chair of the President’s Council of Advisors on Science and Technology (PCAST), along with Caltech chemical engineer Frances Arnold, a 2018 winner of the Nobel Prize in chemistry. Zuber and Arnold will be the first women ever to co-chair PCAST.

Lander, Zuber, Arnold, and other appointees will join Biden in Wilmington, Delaware, on Saturday afternoon, where the president-elect will introduce his team of top advisors on science and technology, domains he has declared as crucial to America’s future. Biden has charged this team with recommending strategies and actions to ensure that the nation maximizes the benefits of science and technology for America’s welfare in the 21st century, including addressing health needs, climate change, national security, and economic prosperity.

“From Covid-19 to climate change, cybersecurity to U.S. competitiveness in innovation, the nation faces urgent challenges whose solutions depend on a broad and deep understanding of the frontiers of science and technology. In that context, it is enormously meaningful that science is being raised to a Cabinet-level position for the first time,” MIT President L. Rafael Reif says. “With his piercing intelligence and remarkable record as scientific pioneer, Eric Lander is a superb choice for this new role. And given her leadership of immensely complex NASA missions and her deep engagement with the leading edge of dozens of scientific domains as MIT’s vice president for research, it is difficult to imagine someone more qualified to co-chair PCAST than Maria Zuber. This is a banner day for science, and for the nation.”

Lander will take a leave of absence from MIT, where he is a professor of biology, and the Broad Institute, which he has led since its 2004 founding. The Broad Institute announced today that Todd Golub, currently its chief scientific officer as well as a faculty member at Harvard Medical School and an investigator at the Dana-Farber Cancer Institute, will succeed Lander as director.

Zuber, the E.A. Griswold Professor of Geophysics in MIT’s Department of Earth, Atmospheric, and Planetary Sciences, will continue to serve as the Institute’s vice president for research, a position she has held since 2013.

Separately, Biden announced earlier this week that he will nominate Gary Gensler, professor of the practice of global economics and management at the MIT Sloan School of Management, as chair of the Securities and Exchange Commission.

Eric Lander

Eric S. Lander, 63, has served since 2004 as founding director of the Broad Institute of MIT and Harvard. A geneticist, molecular biologist, and mathematician, he was one of the principal leaders of the international Human Genome Project from 1990 to 2003, and is committed to attracting, teaching, and mentoring a new generation of scientists to fulfill the promise of genomic insights to benefit human health.

From 2009 to 2017, Lander informed federal policy on science and technology as co-chair of PCAST throughout the two terms of President Barack Obama.

“Our country once again stands at a consequential moment with respect to science and technology, and how we respond to the challenges and opportunities ahead will shape our future for the rest of this century,” Lander says. “President-elect Biden understands the central role of science and technology, and I am deeply honored to have been asked to serve.”

Trained as a mathematician, Lander earned a BA in mathematics from Princeton University in 1978. As a Rhodes Scholar from 1978 to 1981, he attended Oxford University, where he earned his doctorate in mathematics. Lander served on the Harvard Business School faculty from 1981 to 1990, teaching courses on managerial economics, decision analysis, and bargaining.

In 1983, his younger brother, Arthur, a developmental neurobiologist, suggested that, with his interest in coding theory, Lander might be interested in how biological systems, including the brain, encode and process information. Lander began to audit courses at Harvard and to moonlight in laboratories around Harvard and MIT, learning about molecular biology and genetics.

In 1986, he was appointed a Whitehead Fellow of the Whitehead Institute for Biomedical Research, where he started his own laboratory. In 1990, Lander was appointed as a tenured professor in MIT’s Department of Biology and as a member of the Whitehead Institute.

Lander’s honors and awards include the MacArthur Fellowship, the Breakthrough Prize in Life Sciences, the Albany Prize in Medicine and Biological Research, the Gairdner Foundation International Award of Canada, and MIT’s Killian Faculty Achievement Award. He was elected as a member of the U.S. National Academy of Sciences in 1997 and of the U.S. Institute of Medicine in 1999.

Maria Zuber

The daughter of a Pennsylvania state trooper and the granddaughter of coal miners, Maria T. Zuber, 62, has been a member of the MIT faculty since 1995 and MIT’s vice president for research since 2013. She has served since 2012 on the 24-member National Science Board (NSB), the governing body of the National Science Foundation, serving as NSB chair from 2016 to 2019.

Zuber’s own research bridges planetary geophysics and the technology of space-based laser and radio systems. She was the first woman to lead a NASA spacecraft mission, serving as principal investigator of the space agency’s Gravity Recovery and Interior Laboratory (GRAIL) mission, an effort launched in 2008 to map the moon’s gravitational field to answer fundamental questions about the moon’s evolution and internal composition. In all, Zuber has held leadership roles associated with scientific experiments or instrumentation on nine NASA missions since 1990.

As MIT’s vice president for research, Zuber is responsible for research administration and policy. She oversees more than a dozen interdisciplinary research centers, including the David H. Koch Institute for Integrative Cancer Research, the Plasma Science and Fusion Center, the Research Laboratory of Electronics, the Institute for Soldier Nanotechnologies, the MIT Energy Initiative (MITEI), and the Haystack Observatory. She is also responsible for MIT’s research integrity and compliance, and plays a central role in research relationships with the federal government.

“Many of the most pressing challenges facing the nation and the world will require breakthroughs in science and technology,” Zuber says. “An essential element of any solution must be rebuilding trust in science, and I’m thrilled to have the opportunity to work with President-elect Biden and his team to drive positive change.”

Zuber holds a BA in astronomy and geology from the University of Pennsylvania, awarded in 1980, and an ScM and PhD in geophysics from Brown University, awarded in 1983 and 1986, respectively. She has received awards and honors including MIT’s Killian Faculty Achievement Award; the American Geophysical Union’s Harry H. Hess Medal; and numerous NASA awards, including the Distinguished Public Service Medal and the Outstanding Public Leadership Medal. She was elected as a member of the National Academy of Sciences in 2004.

Todd Golub

Todd Golub, 57, will become the next director of the Broad Institute. He joined Dana-Farber and Harvard Medical School in 1997, and is currently a professor of pediatrics at Harvard Medical School and the Charles A. Dana Investigator in Human Cancer Genetics at Dana-Farber.

Golub served as a leader of the Whitehead Institute/MIT Center for Genome Research, the precursor to the Broad Institute. He has also been an investigator with the Howard Hughes Medical Institute, and has served as chair of numerous scientific advisory boards, including at St. Jude Children’s Research Hospital and the National Cancer Institute’s Board of Scientific Advisors.

Golub is also an entrepreneur, having co-founded several biotechnology companies to develop diagnostic and therapeutic products. He has created and applied genomic tools to understand the basis of disease, and to develop new approaches to drug discovery. He has made fundamental discoveries in the molecular basis of human cancer, and has helped develop new approaches to precision medicine.

“Broad is in a stronger scientific and cultural position today than at any point in our 16-year history,” Golub says. “Moreover, the pandemic has pushed us to think differently about nearly every aspect of how we collaborate and deliver on our scientific mission. We are well-positioned to work with the larger scientific community to confront some of the most urgent challenges in biomedicine: from developing novel diagnostics and therapeutics for infectious diseases and cancer, to understanding the genetic basis of cardiovascular disease and mental illness. I am honored to serve as director of this remarkable institution.”

Members of the Broad Institute’s Board of Directors thanked Lander for his lengthy service and expressed optimism in Golub’s ability to build upon that foundation.

“Todd’s deep knowledge of the Broad Institute community, its science, and its mission to propel the understanding and treatment of disease make him the perfect choice for the Institute’s next director,” says Louis Gerstner, Jr., chair of the Broad Institute Board of Directors. “Todd is well-positioned to lead the Institute and our key scientific collaborations forward, and the board is highly confident he will continue the Broad’s culture of innovation, collegiality, and constant renewal.”

Broad board member Shirley Tilghman, professor of molecular biology and public policy and president emerita of Princeton University, adds: “In its 16 years, the Broad has become one of the most unique institutions in the biomedical ecosystem. Under Eric’s and Todd’s leadership, it has developed powerful new methods and made many contributions to genomic medicine that will benefit human health.”

Why cancer cells waste so much energy

MIT study sheds light on the longstanding question of why cancer cells get their energy from fermentation.

Anne Trafton | MIT News Office
January 19, 2021

In the 1920s, German chemist Otto Warburg discovered that cancer cells don’t metabolize sugar the same way that healthy cells usually do. Since then, scientists have tried to figure out why cancer cells use this alternative pathway, which is much less efficient.

MIT biologists have now found a possible answer to this longstanding question. In a study appearing in Molecular Cell, they showed that this metabolic pathway, known as fermentation, helps cells to regenerate large quantities of a molecule called NAD+, which they need to synthesize DNA and other important molecules. Their findings also account for why other types of rapidly proliferating cells, such as immune cells, switch over to fermentation.

“This has really been a hundred-year-old paradox that many people have tried to explain in different ways,” says Matthew Vander Heiden, an associate professor of biology at MIT and associate director of MIT’s Koch Institute for Integrative Cancer Research. “What we found is that under certain circumstances, cells need to do more of these electron transfer reactions, which require NAD+, in order to make molecules such as DNA.”

Vander Heiden is the senior author of the new study, and the lead authors are former MIT graduate student and postdoc Alba Luengo PhD ’18 and graduate student Zhaoqi Li.

Inefficient metabolism

Fermentation is one way that cells can convert the energy found in sugar to ATP, a chemical that cells use to store energy for all of their needs. However, mammalian cells usually break down sugar using a process called aerobic respiration, which yields much more ATP. Cells typically switch over to fermentation only when they don’t have enough oxygen available to perform aerobic respiration.

Since Warburg’s discovery, scientists have put forth many theories for why cancer cells switch to the inefficient fermentation pathway. Warburg originally proposed that cancer cells’ mitochondria, where aerobic respiration occurs, might be damaged, but this turned out not to be the case. Other explanations have focused on the possible benefits of producing ATP in a different way, but none of these theories have gained widespread support.

In this study, the MIT team decided to try to come up with a solution by asking what would happen if they suppressed cancer cells’ ability to perform fermentation. To do that, they treated the cells with a drug that forces them to divert a molecule called pyruvate from the fermentation pathway into the aerobic respiration pathway.

They saw, as others have previously shown, that blocking fermentation slows down cancer cells’ growth. Then, they tried to figure out how to restore the cells’ ability to proliferate, while still blocking fermentation. One approach they tried was to stimulate the cells to produce NAD+, a molecule that helps cells to dispose of the extra electrons that are stripped out when cells make molecules such as DNA and proteins.

When the researchers treated the cells with a drug that stimulates NAD+ production, they found that the cells started rapidly proliferating again, even though they still couldn’t perform fermentation. This led the researchers to theorize that when cells are growing rapidly, they need NAD+ more than they need ATP. During aerobic respiration, cells produce a great deal of ATP and some NAD+. If cells accumulate more ATP than they can use, respiration slows and production of NAD+ also slows.

“We hypothesized that when you make both NAD+ and ATP together, if you can’t get rid of ATP, it’s going to back up the whole system such that you also cannot make NAD+,” Li says.

Therefore, switching to a less efficient method of producing ATP, which allows the cells to generate more NAD+, actually helps them to grow faster. “If you step back and look at the pathways, what you realize is that fermentation allows you to generate NAD+ in an uncoupled way,” Luengo says.

Solving the paradox

The researchers tested this idea in other types of rapidly proliferating cells, including immune cells, and found that blocking fermentation but allowing alternative methods of NAD+ production enabled cells to continue rapidly dividing. They also observed the same phenomenon in nonmammalian cells such as yeast, which perform a different type of fermentation that produces ethanol.

“Not all proliferating cells have to do this,” Vander Heiden says. “It’s really only cells that are growing very fast. If cells are growing so fast that their demand to make stuff outstrips how much ATP they’re burning, that’s when they flip over into this type of metabolism. So, it solves, in my mind, many of the paradoxes that have existed.”

The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say.

The research was funded by the Ludwig Center for Molecular Oncology, the National Science Foundation, the National Institutes of Health, the Howard Hughes Medical Institute, the Medical Research Council, NHS Blood and Transplant, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, Stand Up 2 Cancer, the Lustgarten Foundation, and the MIT Center for Precision Cancer Medicine.

Neuroscientists identify brain circuit that encodes timing of events

Findings suggest this hippocampal circuit helps us to maintain our timeline of memories.

Anne Trafton | MIT News Office
January 12, 2021

When we experience a new event, our brain records a memory of not only what happened, but also the context, including the time and location of the event. A new study from MIT neuroscientists sheds light on how the timing of a memory is encoded in the hippocampus, and suggests that time and space are encoded separately.

In a study of mice, the researchers identified a hippocampal circuit that the animals used to store information about the timing of when they should turn left or right in a maze. When this circuit was blocked, the mice were unable to remember which way they were supposed to turn next. However, disrupting the circuit did not appear to impair their memory of where they were in space.

The findings add to a growing body of evidence suggesting that when we form new memories, different populations of neurons in the brain encode time and place information, the researchers say.

“There is an emerging view that ‘place cells’ and ‘time cells’ organize memories by mapping information onto the hippocampus. This spatial and temporal context serves as a scaffold that allows us to build our own personal timeline of memories,” says Chris MacDonald, a research scientist at MIT’s Picower Institute for Learning and Memory and the lead author of the study.

Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at the RIKEN-MIT Laboratory of Neural Circuit Genetics at the Picower Institute, is the senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences.

Time and place

About 50 years ago, neuroscientists discovered that the brain’s hippocampus contains neurons that encode memories of specific locations. These cells, known as place cells, store information that becomes part of the context of a particular memory.

The other critical piece of context for any given memory is the timing. In 2011, MacDonald and the late Howard Eichenbaum, a professor of psychological and brain sciences at Boston University, discovered cells that keep track of time, in a part of the hippocampus called CA1.

In that study, MacDonald, who was then a postdoc at Boston University, found that these cells showed specific timing-related firing patterns when mice were trained to associate two stimuli — an object and an odor — that were presented with a 10-second delay between them. When the delay was extended to 20 seconds, the cells reorganized their firing patterns to last 20 seconds instead of 10.

“It’s almost like they’re forming a new representation of a temporal context, much like a spatial context,” MacDonald says. “The emerging view seems to be that both place and time cells organize memory by mapping experience to a representation of context that is defined by time and space.”

In the new study, the researchers wanted to investigate which other parts of the brain might be feeding CA1 timing information. Some previous studies had suggested that a nearby part of the hippocampus called CA2 might be involved in keeping track of time. CA2 is a very small region of the hippocampus that has not been extensively studied, but it has been shown to have strong connections to CA1.

To study the links between CA2 and CA1, the researchers used an engineered mouse model in which they could use light to control the activity of neurons in the CA2 region. They trained the mice to run a figure-eight maze in which they would earn a reward if they alternated turning left and right each time they ran the maze. Between each trial, they ran on a treadmill for 10 seconds, and during this time, they had to remember which direction they had turned on the previous trial, so they could do the opposite on the upcoming trial.

When the researchers turned off CA2 activity while the mice were on the treadmill, they found that the mice performed very poorly at the task, suggesting that they could no longer remember which direction they had turned in the previous trial.

“When the animals are performing normally, there is a sequence of cells in CA1 that ticks off during this temporal coding phase,” MacDonald says. “When you inhibit the CA2, what you see is the temporal coding in CA1 becomes less precise and more smeared out in time. It becomes destabilized, and that seems to correlate with them also performing poorly on that task.”

Memory circuits

When the researchers used light to inhibit CA2 neurons while the mice were running the maze, they found little effect on the CA1 “place cells” that allow the mice to remember where they are. The findings suggest that spatial and timing information are encoded preferentially by different parts of the hippocampus, MacDonald says.

“One thing that’s exciting about this work is this idea that spatial and temporal information can operate in parallel and might merge or separate at different points in the circuit, depending on what you need to accomplish from a memory standpoint,” he says.

MacDonald is now planning additional studies of time perception, including how we perceive time under different circumstances, and how our perception of time influences our behavior. Another question he hopes to pursue is whether the brain has different mechanisms for keeping track of events that are separated by seconds and events that are separated by much longer periods of time.

“Somehow the information that we store in memory preserves the sequential order of events across very different timescales, and I’m very interested in how it is that we’re able to do that,” he says.

The research was funded by the RIKEN Center for Brain Science, the Howard Hughes Medical Institute, and the JPB Foundation.

Turning microbiome research into a force for health

A diverse group of researchers is working to turn new discoveries about the trillions of microbes in the body into treatments for a range of diseases.

Zach Winn | MIT News Office
January 8, 2021

The microbiome comprises trillions of microorganisms living on and inside each of us. Historically, some researchers have guessed at its role in human health, but in the last decade or so genetic sequencing techniques have illuminated this galaxy of microorganisms enough to study it in detail.

As researchers unravel the complex interplay between our bodies and microbiomes, they are beginning to appreciate the full scope of the field’s potential for treating disease and promoting health.

For instance, the growing list of conditions that correspond with changes in the microbes of our gut includes type 2 diabetes, inflammatory bowel disease, Alzheimer’s disease, and a variety of cancers.

“In almost every disease context that’s been investigated, we’ve found different types of microbial communities, divergent between healthy and sick patients,” says professor of biological engineering Eric Alm. “The promise [of these findings] is that some of those differences are going to be causal, and intervening to change the microbiome is going to help treat some of these diseases.”

Alm’s lab, in conjunction with collaborators at the Broad Institute of MIT and Harvard, did some of the early work characterizing the gut microbiome and showing its relationship to human health. Since then, microbiome research has exploded, pulling in researchers from far-flung fields and setting new discoveries in motion. Startups are now working to develop microbiome-based therapies, and nonprofit organizations have also sprouted up to ensure these basic scientific advances turn into treatments that benefit the maximum number of people.

“The first chapter in this field, and our history, has been validating this modality,” says Mark Smith PhD ’14, a co-founder of OpenBiome, which processes stool donations for hospitals to conduct stool transplants for patients battling gut infection. Smith is also currently CEO of the startup Finch Therapeutics, which is developing microbiome-based treatments. “Until now, it’s been about the promise of the microbiome. Now I feel like we’ve delivered on the first promise. The next step is figuring out how big this gets.”

An interdisciplinary foundation

MIT’s prominent role in microbiome research came, in part, through its leadership in a field that may at first seem unrelated. For decades, MIT has made important contributions to microbial ecology, led by work in the Parsons Laboratory in the Department of Civil and Environmental Engineering and by scientists including Institute Professor Penny Chisholm.

Ecologists who use complex statistical techniques to study the relationships between organisms in different ecosystems are well-equipped to study the behavior of different bacterial strains in the microbiome.

Not that ecologists — or anyone else — initially had much to study involving the human microbiome, which was essentially a black box to researchers well into the 2000s. But the Human Genome Project led to faster, cheaper ways to sequence genes at scale, and a group of researchers including Alm and visiting professor Martin Polz began using those techniques to decode the genomes of environmental bacteria around 2008.

Those techniques were first pointed at the bacteria in the gut microbiome as part of the Human Microbiome Project, which began in 2007 and involved research groups from MIT and the Broad Institute.

Alm first got pulled into microbiome research by the late biological engineering professor David Schauer as part of a research project with Boston Children’s Hospital. It didn’t take much to get up to speed: Alm says the number of papers explicitly referencing the microbiome at the time could be read in an afternoon.

The collaboration, which included Ramnik Xavier, a core institute member of the Broad Institute, led to the first large-scale genome sequencing of the gut microbiome to diagnose inflammatory bowel disease. The research was funded, in part, by the Neil and Anna Rasmussen Family Foundation.

The study offered a glimpse into the microbiome’s diagnostic potential. It also underscored the need to bring together researchers from diverse fields to dig deeper.

Taking an interdisciplinary approach is important because, after next-generation sequencing techniques are applied to the microbiome, a large amount of computational biology and statistical methods are still needed to interpret the resulting data — the microbiome, after all, contains more genes than the human genome. One catalyst for early microbiome collaboration was the Microbiology Graduate PhD Program, which recruited microbiology students to MIT and introduced them to research groups across the Institute.

As microbiology collaborations increased among researchers from different department and labs, Neil Rasmussen, a longtime member of the MIT Corporation and a member of the visiting committees for a number of departments, realized there was still one more component needed to turn microbiome research into a force for human health.

“Neil had the idea to find all the clinical researchers in the [Boston] area studying diseases associated with the microbiome and pair them up with people like [biological engineers, mathematicians, and ecologists] at MIT who might not know anything about inflammatory bowel disease or microbiomes but had the expertise necessary to solve big problems in the field,” Alm says.

In 2014, that insight led the Rasmussen Foundation to support the creation of the Center for Microbiome Informatics and Therapeutics (CMIT), one of the first university-based microbiome research centers in the country.

Tami Lieberman, the Hermann L. F. von Helmholtz Career Development Professor at MIT, whose background is in ecology, says CMIT was a big reason she joined MIT’s faculty in 2018. Lieberman has developed new genomic approaches to study how bacteria mutate in healthy and sick individuals, with a particular focus on the skin microbiome.

Laura Kiessling, a chemist who has been recognized for contributions to our understanding of cell surface interactions, was also quick to joint CMIT. Kiessling, the Novartis Professor of Chemistry, has made discoveries relating to microbial mechanisms that influence immune function. Both Lieberman and Kiessling are also members of the Broad Institute.

Today, CMIT, co-directed by Alm and Xavier, facilitates collaborations between researchers and clinicians from hospitals around the country in addition to supporting research groups in the area. That work has led to hundreds of ongoing clinical trials that promise to further elucidate the microbiome’s connection to a broad range of diseases.

Fulfilling the promise of the microbiome

Researchers don’t yet know what specific strains of bacteria can improve the health of people with microbiome-associated diseases. But they do know that fecal matter transplants, which carry the full spectrum of gut bacteria from a healthy donor, can help patients suffering from certain diseases.

The nonprofit organization OpenBiome, founded by a group from MIT including Smith and Alm, launched in 2012 to help expand access to fecal matter transplants by screening donors for stool collection then processing, storing, and shipping samples to hospitals. Today OpenBiome works with more than 1,000 hospitals, and its success in the early days of the field shows that basic microbiome research, when paired with clinical trials like those happening at CMIT, can quickly lead to new treatments.

“You start with a disease, and if there’s a microbiome association, you can start a small trial to see if fecal transplants can help patients right away,” Alm explains. “If that becomes an effective treatment, while you’re rolling it out you can be doing the genomics to figure out how to make it better. So you can translate therapeutics into patients more quickly than when you’re developing small-molecule drugs.”

Another nonprofit project launched out of MIT, the Global Microbiome Conservancy, is collecting stool samples from people living nonindustrialized lifestyles around the world, whose guts have much different bacterial makeups and thus hold potential for advancing our understanding of host-microbiome interactions.

A number of private companies founded by MIT alumni are also trying to harness individual microbes to create new treatments, including, among others, Finch Therapeutics founded by Mark Smith; Concerto Biosciences, co-founded by Jared Kehe PhD ’20 and Bernardo Cervantes PhD ’20; BiomX, founded by Associate Professor Tim Lu; and Synlogic, founded by Lu and Jim Collins, the Termeer Professor of Medical Engineering and Science at MIT.

“There’s an opportunity to more precisely change a microbiome,” explains CMIT’s Lieberman. “But there’s a lot of basic science to do to figure out how to tweak the microbiome in a targeted way. Once we figure out how to do that, the therapeutic potential of the microbiome is quite limitless.”

Explained: Why RNA vaccines for Covid-19 raced to the front of the pack

Many years of research have enabled scientists to quickly synthesize RNA vaccines and deliver them inside cells.

Anne Trafton | MIT News Office
December 11, 2020

Developing and testing a new vaccine typically takes at least 12 to 18 months. However, just over 10 months after the genetic sequence of the SARS-CoV-2 virus was published, two pharmaceutical companies applied for FDA emergency use authorization of vaccines that appear to be highly effective against the virus.

Both vaccines are made from messenger RNA, the molecule that cells naturally use to carry DNA’s instructions to cells’ protein-building machinery. A vaccine based on mRNA has never been approved by the FDA before. However, many years of research have gone into RNA vaccines, which is one reason why scientists were able to start testing such vaccines against Covid-19 so quickly. Once the viral sequences were revealed in January, it took just days for pharmaceutical companies Moderna and Pfizer, along with its German partner BioNTech, to generate mRNA vaccine candidates.

“What’s particularly unique to mRNA is the ability to rapidly generate vaccines against new diseases. That I think is one of the most exciting stories behind this technology,” says Daniel Anderson, a professor of chemical engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

Most traditional vaccines consist of either killed or weakened forms of a virus or bacterium. These provoke an immune response that allows the body to fight off the actual pathogen later on.

Instead of delivering a virus or a viral protein, RNA vaccines deliver genetic information that allows the body’s own cells to produce a viral protein. Synthetic mRNA that encodes a viral protein can borrow this machinery to produce many copies of the protein. These proteins stimulate the immune system to mount a response, without posing any risk of infection.

A key advantage of mRNA is that it is very easy to synthesize once researchers know the sequence of the viral protein they want to target. Most vaccines for SARS-CoV-2 provoke an immune response that targets the coronavirus spike protein, which is found on the surface of the virus and gives the virus its characteristic spiky shape. Messenger RNA vaccines encode segments of the spike protein, and those mRNA sequences are much easier to generate in the lab than the spike protein itself.

“With traditional vaccines, you have to do a lot of development. You need a big factory to make the protein, or the virus, and it takes a long time to grow them,” says Robert Langer, the David H. Koch Institute Professor at MIT, a member of the Koch Institute, and one of the founders of Moderna. “The beauty of mRNA is that you don’t need that. If you inject nanoencapsulated mRNA into a person, it goes into the cells, and then the body is your factory. The body takes care of everything else from there.”

Langer has spent decades developing novel ways to deliver medicines, including therapeutic nucleic acids such as RNA and DNA. In the 1970s, he published the first study showing that it was possible to encapsulate nucleic acids, as well as other large molecules, in tiny particles and deliver them into the body. (Work by MIT Institute Professor Phillip Sharp and others on RNA splicing, which also laid groundwork for today’s mRNA vaccines, began in the ’70s as well.)

“It was very controversial at the time,” Langer recalls. “Everybody told us it was impossible, and my first nine grants were rejected. I spent about two years working on it, and I found over 200 ways to get it to not work. But then eventually I did find a way to get it to work.”

That paper, which appeared in Nature in 1976, showed that tiny particles made of synthetic polymers could safely carry and slowly release large molecules such as proteins and nucleic acids. Later, Langer and others showed that when polyethylene glycol (PEG) was added to the surface of nanoparticles, they could last in the body for much longer, instead of being destroyed almost immediately.

In subsequent years, Langer, Anderson, and others have developed fatty molecules called lipid nanoparticles that are also very effective at delivering nucleic acids. These carriers protect RNA from being broken down in the body and help to ferry it through cell membranes. Both the Moderna and Pfizer RNA vaccines are carried by lipid nanoparticles with PEG.

“Messenger RNA is a large hydrophilic molecule. It doesn’t naturally enter cells by itself, and so these vaccines are wrapped up in nanoparticles that facilitate their delivery inside of cells. This allows the RNA to be delivered inside of cells, and then translated into proteins,” Anderson says.

In 2018, the FDA approved the first lipid nanoparticle carrier for RNA, which was developed by Alnylam Pharmaceuticals to deliver a type of RNA called siRNA. Unlike mRNA, siRNA silences its target genes, which can benefit patients by turning off mutated genes that cause disease.

One drawback to mRNA vaccines is that they can break down at high temperatures, which is why the current vaccines are stored at such cold temperatures.  Pfizer’s SARS-CoV-2 vaccine has to be stored at -70 degrees Celsius (-94 degrees Fahrenheit), and the Moderna vaccine at -20 C (-4 F). One way to make RNA vaccines more stable, Anderson points out, is to add stabilizers and remove water from the vaccine through a process called lyophilization, which has been shown to allow some mRNA vaccines to be stored in a refrigerator instead of a freezer.

The striking effectiveness of both of these Covid-19 vaccines in phase 3 clinical trials (roughly 95 percent) offers hope that not only will those vaccines help to end the current pandemic, but also that in the future, RNA vaccines may help in the fight against other diseases such as HIV and cancer, Anderson says.

“People in the field, including myself, saw a lot of promise in the technology, but you don’t really know until you get human data. So to see that level of protection, not just with the Pfizer vaccine but also with Moderna, really validates the potential of the technology — not only for Covid, but also for all these other diseases that people are working on,” he says. “I think it’s an important moment for the field.”

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.