Author: mantulin

Neuroscientists find memory cells that help us interpret new situations

Neurons that store abstract representations of past experiences are activated when a new, similar event takes place.

Anne Trafton | MIT News Office
April 6, 2020

Imagine you are meeting a friend for dinner at a new restaurant. You may try dishes you haven’t had before, and your surroundings will be completely new to you. However, your brain knows that you have had similar experiences — perusing a menu, ordering appetizers, and splurging on dessert are all things that you have probably done when dining out.

MIT neuroscientists have now identified populations of cells that encode each of these distinctive segments of an overall experience. These chunks of memory, stored in the hippocampus, are activated whenever a similar type of experience takes place, and are distinct from the neural code that stores detailed memories of a specific location.

The researchers believe that this kind of “event code,” which they discovered in a study of mice, may help the brain interpret novel situations and learn new information by using the same cells to represent similar experiences.

“When you encounter something new, there are some really new and notable stimuli, but you already know quite a bit about that particular experience, because it’s a similar kind of experience to what you have already had before,” says Susumu Tonegawa, a professor of biology and neuroscience at the RIKEN-MIT Laboratory of Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory.

Tonegawa is the senior author of the study, which appears today in Nature Neuroscience. Chen Sun, an MIT graduate student, is the lead author of the paper. New York University graduate student Wannan Yang and Picower Institute technical associate Jared Martin are also authors of the paper.

Encoding abstraction

It is well-established that certain cells in the brain’s hippocampus are specialized to store memories of specific locations. Research in mice has shown that within the hippocampus, neurons called place cells fire when the animals are in a specific location, or even if they are dreaming about that location.

In the new study, the MIT team wanted to investigate whether the hippocampus also stores representations of more abstract elements of a memory. That is, instead of firing whenever you enter a particular restaurant, such cells might encode “dessert,” no matter where you’re eating it.

To test this hypothesis, the researchers measured activity in neurons of the CA1 region of the mouse hippocampus as the mice repeatedly ran a four-lap maze. At the end of every fourth lap, the mice were given a reward. As expected, the researchers found place cells that lit up when the mice reached certain points along the track. However, the researchers also found sets of cells that were active during one of the four laps, but not the others. About 30 percent of the neurons in CA1 appeared to be involved in creating this “event code.”

“This gave us the initial inkling that besides a code for space, cells in the hippocampus also care about this discrete chunk of experience called lap 1, or this discrete chunk of experience called lap 2, or lap 3, or lap 4,” Sun says.

To further explore this idea, the researchers trained mice to run a square maze on day 1 and then a circular maze on day 2, in which they also received a reward after every fourth lap. They found that the place cells changed their activity, reflecting the new environment. However, the same sets of lap-specific cells were activated during each of the four laps, regardless of the shape of the track. The lap-encoding cells’ activity also remained consistent when laps were randomly shortened or lengthened.

“Even in the new spatial locations, cells still maintain their coding for the lap number, suggesting that cells that were coding for a square lap 1 have now been transferred to code for a circular lap 1,” Sun says.

The researchers also showed that if they used optogenetics to inhibit sensory input from a part of the brain called the medial entorhinal cortex (MEC), lap-encoding did not occur. They are now investigating what kind of input the MEC region provides to help the hippocampus create memories consisting of chunks of an experience.

Two distinct codes

These findings suggest that, indeed, every time you eat dinner, similar memory cells are activated, no matter where or what you’re eating. The researchers theorize that the hippocampus contains “two mutually and independently manipulatable codes,” Sun says. One encodes continuous changes in location, time, and sensory input, while the other organizes an overall experience into smaller chunks that fit into known categories such as appetizer and dessert.

“We believe that both types of hippocampal codes are useful, and both are important,” Tonegawa says. “If we want to remember all the details of what happened in a specific experience, moment-to-moment changes that occurred, then the continuous monitoring is effective. But on the other hand, when we have a longer experience, if you put it into chunks, and remember the abstract order of the abstract chunks, that’s more effective than monitoring this long process of continuous changes.”

The new MIT results “significantly advance our knowledge about the function of the hippocampus,” says Gyorgy Buzsaki, a professor of neuroscience at New York University School of Medicine, who was not part of the research team.

“These findings are significant because they are telling us that the hippocampus does a lot more than just ‘representing’ space or integrating paths into a continuous long journey,” Buzsaki says. “From these remarkable results Tonegawa and colleagues conclude that they discovered an ‘event code,’ dedicated to organizing experience by events, and that this code is independent of spatial and time representations, that is, jobs also attributed to the hippocampus.”

Tonegawa and Sun believe that networks of cells that encode chunks of experiences may also be useful for a type of learning called transfer learning, which allows you to apply knowledge you already have to help you interpret new experiences or learn new things. Tonegawa’s lab is now working on trying to find cell populations that might encode these specific pieces of knowledge.

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

A stopgap measure to treat respiratory distress

Repurposing a drug used for blood clots may help Covid-19 patients in danger of respiratory failure, researchers suggest.

Anne Trafton | MIT News Office
March 26, 2020

Researchers at MIT and the University of Colorado at Denver have proposed a stopgap measure that they believe could help Covid-19 patients who are in acute respiratory distress. By repurposing a drug that is now used to treat blood clots, they believe they could help people in cases where a ventilator is not helping, or if a ventilator is not available.

Three hospitals in Massachusetts and Colorado are developing plans to test this approach in severely ill Covid-19 patients. The drug, a protein called tissue plasminogen activator (tPA), is commonly given to heart attack and stroke victims. The approach is based on emerging data from China and Italy that Covid-19 patients have a profound disorder of blood clotting that is contributing to their respiratory failure.

“If this were to work, which I hope it will, it could potentially be scaled up very quickly, because every hospital already has it in their pharmacy,” says Michael Yaffe, a David H. Koch Professor of Science at MIT. “We don’t have to make a new drug, and we don’t have to do the same kind of testing that you would have to do with a new agent. This is a drug that we already use. We’re just trying to repurpose it.”

Yaffe, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and an intensive care physician at Boston’s Beth Israel Deaconess Medical Center/Harvard Medical School, is the senior author of a paper describing the new approach.

The paper, which appears in the Journal of Trauma and Acute Care Surgery, was co-authored by Christopher Barrett, a surgeon at Beth Israel Deaconess and a visiting scientist at MIT; Hunter Moore, Ernest Moore, Peter Moore, and Robert McIntyre of the University of Colorado at Denver; Daniel Talmor of Beth Israel Deaconess; and Frederick Moore of the University of Florida.

Breaking up clots

In one large-scale study of the Covid-19 outbreak in Wuhan, China, it was found that 5 percent of patients required intensive care and 2.3 percent required a ventilator. Many doctors and public health officials in the United States worry that there may not be enough ventilators for all Covid-19 patients who will need them. In China and Italy, a significant number of the patients who required a ventilator went on to die of respiratory failure, despite maximal support, indicating that there is a need for additional treatment approaches.

The treatment that the MIT and University of Colorado team now proposes is based on many years of research into what happens in the lungs during respiratory failure. In such patients, blood clots often form in the lungs. Very small clots called microthrombi can also form in the blood vessels of the lungs. These tiny clots prevent blood from reaching the airspaces of the lungs, where blood normally becomes oxygenated.

The researchers believe that tPA, which helps to dissolve blood clots, may help patients in acute respiratory distress. A natural protein found in our bodies, tPA converts plasminogen to an enzyme called plasmin, which breaks down clots. Larger amounts are often given to heart attack patients or stroke victims to dissolve the clot causing the heart attack or stroke.

Animal experiments, and one human trial, have shown potential benefits of this approach in treating respiratory distress. In the human trial, performed in 2001, 20 patients who were in respiratory failure following trauma or sepsis were given drugs that activate plasminogen (urokinase or streptokinase, but not tPA). All of the patients in the trial had respiratory distress so severe that they were not expected to survive, but 30 percent of them survived following treatment.

That is the only study using plasminogen activators to treat respiratory failure in humans to date, largely because improved ventilator strategies have been working well. This appears not to be the case for many patients with Covid-19, Yaffe says.

The idea to try this treatment in Covid-19 patients arose, in part, because the Colorado and MIT research team has spent the last several years studying the inflammation and abnormal bleeding that can occur in the lungs following traumatic injuries. It turns out that Covid-19 patients also suffer from inflammation-linked tissue damage, which has been seen in autopsy results from those patients and may contribute to clot formation.

“What we are hearing from our intensive care colleagues in Europe and in New York is that many of the critically ill patients with Covid-19 are hypercoagulable, meaning that they are clotting off their IVs, and having kidney and heart failure from blood clots, in addition to lung failure.  There’s plenty of basic science to support the idea that this concept should be beneficial,” Yaffe says. “The tricky part, of course, is figuring out the right dose and route of administration. But the target we are going after is well-validated.”

Potential benefits

The researchers will test tPA in patients under the FDA’s “compassionate use” program, which allows experimental drugs to be used in cases where there are no other treatment options. If the drug appears to help in an initial set of patients, its use could be expanded further, Yaffe says.

“We learned that the clinical trial will be funded by BARDA [the Biomedical Advanced Research and Development Authority], and that Francis Collins, the NIH director, was briefed on the approach yesterday afternoon,” he says. “Genentech, the manufacturer of tPA, has already donated the drug for the initial trial, and indicated that they will rapidly expand access if the initial patient response is encouraging.”

Based on the latest data from their colleagues in Colorado, these groups plan to deliver the drug both intravenously and/or instill it directly into the airways. The intravenous route is currently used for stroke and heart attack patients. Their idea is to give one dose rapidly, over a two-hour period, followed by an equivalent dose given more slowly over 22 hours. Applied BioMath, a company spun out by former MIT researchers, is now working on computational models that may help to refine the dosing schedule.

“If it were to work, and we don’t yet know if it will, it has a lot of potential for rapid expansion,” Yaffe says. “The public health benefits are obvious. We might get people off ventilators quicker, and we could potentially prevent people from needing to go on a ventilator.”

The hospitals planning to test this approach are Beth Israel Deaconess, the University of Colorado Anschultz Medical Campus, and Denver Health. The research that led to this proposal was funded by the National Institutes of Health and the Department of Defense Peer Reviewed Medical Research Program.

Thank you for your patients

An unusual synergy between cancer researchers, clinical centers, and industry leads to promising clinical trials for a new combination therapy for prostate cancer.

Bendta Schroeder | Koch Institute
March 21, 2020

As Jesse Patterson, an MIT research scientist, and Frank Lovell, a finance industry retiree with a penchant for travel, chatted in the Koch Institute auditorium after a public lecture, they realized the anomaly of the experience: Cancer patients rarely get to meet researchers working on their treatments, and cancer researchers rarely get to put a name and a face to the people they aim to help through their work.

Lovell was participating in a clinical trial for a prostate cancer therapy that combines the widely-used targeted therapy abiraterone with the Plk1 inhibitor onvansertib. Patterson, working in the laboratory of Professor Michael Yaffe, the David H. Koch Professor of Science and director of the MIT Center for Precision Cancer Medicine, played a significant role in identifying the new drug combination and its powerful potential.

While their encounter was indeed fortunate, it was not random. They never would have met if not for the human synergy showcased at that evening’s SOLUTIONS with/in/sight event, the result of collaborative relationships built between research labs, clinical centers, and industry. Patterson and Yaffe were on hand to tell the story of the science behind their new drug combination, and were joined by some of the partners who helped translate their results into a clinical trial: David Einstein, clinical oncologist at Beth Israel Deaconess Medical Center, and Mark Erlander, chief scientific officer of Trovagene Oncology, the biotech company that developed onvansertib.

Network synergy

The need for new prostate cancer therapies is acute. Prostate cancer is the leading diagnosis among men for non-skin cancer and the second-leading cancer killer among men in the United States. Abiraterone works by shutting off androgen synthesis and interfering with the androgen receptor pathway, which plays a crucial role in prostate cancer cells’ ability to survive and divide. However, cancer cells eventually evolve resistance to abiraterone. New, more powerful drug combinations are needed to circumvent or delay the development of resistance.

Patterson and his colleagues in the Yaffe lab hypothesized that by targeting both the androgen receptor and other pathways critical to cancer cell proliferation, they could produce a synergistic effect — that is, a combination effect that is much greater than the sum of each drug’s effect by itself. Plk1, a pathway critical to each stage of cell division, was of longstanding interest to the Yaffe group, and was among those Patterson strategically selected for investigation as a potential partner target for androgen receptor. In screens of prostate cancer cell lines and in xenograft tumors, the researchers found that abiraterone and Plk1 inhibitors both interfere with cell division when delivered singly, but that together, those effects are amplified and far more often lethal to cancer cells.

An unexpected phone call from Mark Erlander at Trovagene, a San Diego-based clinical-stage biotech company, was instrumental in translating the Yaffe Lab’s research results into clinical trials.

Erlander had learned that MIT held a patent for the combination of Plk1 inhibitors and anti-androgens for any cancer — the result of Yaffe Lab studies. Although he did not know Yaffe personally and lived a continent away, Erlander picked up the phone and invited Yaffe for coffee. “This was worth flying across the country,” Erlander said.

Still in scrubs, Yaffe, who is an attending surgeon at Beth Israel Deaconess Medical Center in addition to his academic roles, chatted with Erlander during his shift break at the hospital. The new collaboration was on its way.

Speaking Frankly

While Erlander had the Plk1 inhibitor and the Yaffe Lab had the science behind it, they were still missing an important component of any clinical trial: patients. Yaffe enlisted doctors David Einstein and Steven Balk, both at Beth Israel Deaconess Medical Center and Dana Farber/Harvard Cancer Center, with whom he had worked on related research supported by the Bridge Project, to bring clinical translation expertise and patient access.

By the time clinical trials began in 2019, Frank Lovell was ready for a new treatment. When his prostate cancer was first diagnosed about a decade ago, he was treated with surgery and radiation. When the cancer came back five years later, he received a hormonal treatment that stopped working within three years. He started to see Einstein, an oncologist who specialized in novel therapies, and tried yet another treatment, this one losing effectiveness after a year. Then he joined Einstein’s trial.

For Lovell, the new combination of drugs was “effective in a wonderful way.” Many of the patients in the trial — 72 percent of those who completed phase 2 — showed declining or stabilized levels of prostate-specific androgen (PSA), indicating a positive response to the treatment. Lovell’s PSA levels stabilized, too, and he reports that he experienced very few side effects.

But most importantly, noted Lovell, “I say thank you to Dr. Einstein, Dr. Patterson, and Dr. Yaffe. They brought me hope and time.”

The gratitude is mutual.

“I especially want to thank Frank and all the patients like him who have volunteered to be on these clinical trials,” says Yaffe. “Without patients like Frank, we would never know how to better treat these types of cancers.”

Lovell is no longer in the trial for now, but enjoying making his rounds from Cape Cod in the summer; to Paris and Cannes, France, and then Hawaii in the autumn; and to Naples, Florida, in the winter, on top of visiting with family and a wide circle of friends. “Illness has not stopped me from living a normal life,” Lovell said. “You wouldn’t think I was sick.”

Meanwhile, Yaffe, Patterson, and their research collaborators are still at work. They are optimizing drug delivery regimens to maximize the time on treatment and minimize toxicity, as well as finding biomarkers that help identify which patients will best respond to the combination. They are also looking to understand the mechanism behind the synergy better, which in turn may help them find more effective partners for onvansertib, and to identify other cancer types, such as ovarian cancer, for which the combination may be effective.

Bacterial enzyme could become a new target for antibiotics

Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Anne Trafton | MIT News Office
March 17, 2020

MIT and Harvard University chemists have discovered the structure of an unusual bacterial enzyme that can break down an amino acid found in collagen, which is the most abundant protein in the human body.

The enzyme, known as hydroxy-L-proline dehydratase (HypD), has been found in a few hundred species of bacteria that live in the human gut, including Clostridioides difficile. The enzyme performs a novel chemical reaction that dismantles hydroxy-L-proline, the molecule that gives collagen its tough, triple-helix structure.

Now that researchers know the structure of the enzyme, they can try to develop drugs that inhibit it. Such a drug could be useful in treating C. difficile infections, which are resistant to many existing antibiotics.

“This is very exciting because this enzyme doesn’t exist in humans, so it could be a potential target,” says Catherine Drennan, an MIT professor of chemistry and biology and a Howard Hughes Medical Institute Investigator. “If you could potentially inhibit that enzyme, that could be a unique antibiotic.”

Drennan and Emily Balskus, a professor of chemistry and chemical biology at Harvard University, are the senior authors of the study, which appears today in the journal eLife. MIT graduate student Lindsey Backman and former Harvard graduate student Yolanda Huang are the lead authors of the study.

A difficult reaction

The HypD enzyme is part of a large family of proteins called glycyl radical enzymes. These enzymes work in an unusual way, by converting a molecule of glycine, the simplest amino acid, into a radical — a molecule that has one unpaired electron. Because radicals are very unstable and reactive, they can be used as cofactors, which are molecules that help drive a chemical reaction that would otherwise be difficult to perform.

These enzymes work best in environments that don’t have a lot of oxygen, such as the human gut. The Human Microbiome Project, which has sequenced thousands of bacterial genes from species found in the human gut, has yielded several different types of glycyl radical enzymes, including HypD.

In a previous study, Balskus and researchers at the Broad Institute of MIT and Harvard discovered that HypD can break down hydroxy-L-proline into a precursor of proline, one of the essential amino acids, by removing the hydroxy modification as a molecule of water. These bacteria can ultimately use proline to generate ATP, a molecule that cells use to store energy, through a process called amino acid fermentation.

HypD has been found in about 360 species of bacteria that live in the human gut, and in this study, Drennan and her colleagues used X-ray crystallography to analyze the structure of the version of HypD found in C. difficile. In 2011, this species of bacteria was responsible for about half a million infections and 29,000 deaths in the United States.

The researchers were able to determine which region of the protein forms the enzyme’s “active site,” which is where the reaction occurs. Once hydroxy-L-proline binds to the active site, a nearby glycine molecule forms a glycyl radical that can pass that radical onto the hydroxy-L-proline, leading to the elimination of the hydroxy group.

Removing a hydroxy group is usually a difficult reaction that requires a large input of energy.

“By transferring a radical to hydroxy-L-proline, it lowers the energetic barrier and allows for that reaction to occur pretty rapidly,” Backman says. “There’s no other known enzyme that can perform this kind of chemistry.”

New drug target

It appears that once bacteria perform this reaction, they divert proline into their own metabolic pathways to help them grow. Therefore, blocking this enzyme could slow down the bacteria’s growth. This could be an advantage in controlling C. difficile, which often exists in small numbers in the human gut but can cause illness if the population becomes too large. This sometimes occurs after antibiotic treatment that wipes out other species and allows C. difficile to proliferate.

“C. difficile can be in your gut without causing problems — it’s when you have too much of it compared to other bacteria that it becomes more problematic,” Drennan says. “So, the idea is that by targeting this enzyme, you could limit the resources of C. difficile, without necessarily killing it.”

The researchers now hope to begin designing drug candidates that could inhibit HypD, by targeting the elements of the protein structure that appear to be the most important in carrying out its function.

The research was funded by the National Institutes of Health, a National Science Foundation Graduate Research Fellowship, Harvard University, a Packard Fellowship for Science and Engineering, the NSERC Postgraduate Scholarship-Doctoral Program, an Arnold O. Beckman Postdoctoral Fellowship, a Dow Fellowship, and a Gilliam Fellowship from the Howard Hughes Medical Institute.

QS World University Rankings rates MIT No. 1 in 12 subjects for 2020

Institute ranks second in five subject areas.

MIT News Office
March 4, 2020

MIT has been honored with 12 No. 1 subject rankings in the QS World University Rankings for 2020.

The Institute received a No. 1 ranking in the following QS subject areas: Architecture/Built Environment; Chemistry; Computer Science and Information Systems; Chemical Engineering; Civil and Structural Engineering; Electrical and Electronic Engineering; Mechanical, Aeronautical and Manufacturing Engineering; Linguistics; Materials Science; Mathematics; Physics and Astronomy; and Statistics and Operational Research.

MIT also placed second in five subject areas: Accounting and Finance; Biological Sciences; Earth and Marine Sciences; Economics and Econometrics; and Environmental Sciences.

Quacquarelli Symonds Limited subject rankings, published annually, are designed to help prospective students find the leading schools in their field of interest. Rankings are based on research quality and accomplishments, academic reputation, and graduate employment.

MIT has been ranked as the No. 1 university in the world by QS World University Rankings for eight straight years.

A force for health equity

Through on-site projects in developing countries and internships in the business world, Kendyll Hicks explores the political and economic drivers of global health.

Becky Ham | MIT News Office
March 1, 2020

After spending three weeks in Kenya working on water issues with Maasai women, Kendyll Hicks was ready to declare it her favorite among the international projects she’s participated in through MIT.

As a volunteer with the nonprofit Mama Maji, Hicks spoke about clean water, menstrual hygiene, and reproductive health with local women, sharing information that would enable them to become community leaders. “In rural Kenya, women are disproportionately affected by water issues,” she explains. “This is one way to give them a voice in societies that traditionally will silence them.”

The team also planned to build a rainwater harvesting tank, but climate change has transformed Kenya’s dry season into a rainy one, and it was too wet to break ground for the project. During her stay, Hicks lived in the home of the first female chief of the Masaai, Beatrice Kosiom, whom Hicks describes as “simultaneously a political animal and the most down-to-earth-person.” It was this close contact with the community that made the project especially fulfilling.

During MIT’s Independent Activities Period, Hicks also has traveled to South Africa to learn more about the cultural and biological determinants of that country’s HIV/AIDS epidemic, and to Colombia to lead an entrepreneurial initiative among small-scale coffee farmers. Hicks joined the Kenya trip after taking an MIT D-Lab class on water, sanitation, and hygiene. Each experience has been successively more hands-on, she says.

“I’ve been drawn to these experiences mainly because I love school, and I love the classroom experience,” Hicks says. “But it just can’t compare to living with people and understanding their way of life and the issues they face every day.”

Hicks, a senior majoring in computer science and molecular biology, says she has shifted her focus during her time at MIT from more incremental technical discoveries to addressing larger forces that affect how those discoveries contribute — or fail to contribute — to global health.

Her love of biology began with animals and zoology, later expanding into an interest in medicine. “Humans are these amazing machines that have been crafted by nature and evolution, and we have all these intricacies and mechanisms that I knew I wanted to study further,” Hicks says.

At the same time, she says, “I’ve always been interested in health care and medicine, and the main impetus behind that is the fact that when someone you love is sick, or if you’re sick, you’ll do whatever you can.”

As a first-year student she worked in the Lippard Lab at MIT, helping to synthesize and test anticancer compounds, but she soon decided that lab work wasn’t the right path for her. “I made the realization that health care and medicine are extremely political,” she recalls. “Health policy, health economics, law — those can be the drivers of real large-scale change.”

To learn more about those drivers, Hicks has worked two summers at the management consulting firm McKinsey and Company, and will take a full-time position with the company after graduation.

“As someone immersed in the world of science and math and tech, I had this lingering insecurity that I didn’t know that much about this entirely different but super-important area,” she says. “I thought it would be important to understand what motivates business and the private sector, since that can have a huge effect on health care and helping communities that are often disenfranchised.”

Hicks wants to steer her work at McKinsey toward their health care and hospital sector, as well as their growing global health sector. Over the long term, she is also interested in continuing fieldwork that involves science, poverty eradication, and international development.

“Being at MIT, it’s like this hub of tech, trying to venture further into novel breakthroughs and innovations, and I think it’s amazing,” Hicks says. “But as I have started to garner more of an interest in politics and economics and the highly socialized aspects of science, I would say it’s important to take a pause before venturing further and deeper into that realm, to make sure that you truly understand the downstream effects of what you are developing.”

“Those effects can be negative,” she adds, “and they oftentimes impact communities that already are systematically and institutionally oppressed.”

Hicks joined MIT’s Black Students Union as a first-year student and now serves as the BSU Social and Cultural Co-Chair. In the role, she is responsible for planning the annual Ebony Affair fly-in program, which brings more than 30 black high school students to campus each year to participate in workshops, tour labs, and join a gala celebration with BSU students, faculty, and staff. “We’re doing our best as a community to convince young bright black minds to come to a place like MIT,” she says.

It worked for Hicks: She participated in Ebony Affair as a high schooler, and the experience cemented her decision to attend. “When I saw everyone showing out and having such pride in being black and being at MIT, I was like, ‘OK, I want to be a part of that,’” she recalls.

Last year, Hicks planned BSU’s first Black Homecoming event, a barbecue that brought together current and former black MIT students — some who attended the school 50 years ago. The event was a celebration of support and a way to strengthen the BSU network. “You have to do what you can to cultivate communities wherever you are, and that’s what I’ve tried to do here at MIT,” she says.

Hicks also served as the Black Women’s Alliance alumni relations chair and GlobeMed’s campaigns co-director, and was on the Undergraduate Association Diversity and Inclusion Committee. She has discovered a love of event organizing and leadership at MIT, although it has been a change of pace from her former shy, “hyper-bookworm” self, she says.

“I have realized that in my career that I really want to do a lot of good and affect a lot of change in people’s lives, and in order to do that, you kind of have to be this way.”

Why C. difficile infection spreads despite increased sanitation practices

Research underscores infection is not a common hospital transmission.

Maria Iacobo | Department of Civil and Environmental Engineering
February 20, 2020

New research from MIT suggests the risk of becoming colonized by Clostridium difficile (C. difficile) increases immediately following gastrointestinal (GI) disturbances that result in diarrhea.

Once widely considered an antibiotic- and hospital-associated pathogen, recent research into C. difficile has shown the infection is more frequently acquired outside of hospitals. Now, a team of researchers has shown that GI disturbances, such as those caused by food poisoning and laxative abuse, trigger susceptibility to colonization by C. difficile, and carriers remain C. difficile-positive for a year or longer.

“Our work helps show why the hospital and antibiotic association of C. difficile infections is an oversimplification of the risks and transmission patterns, and helps reconcile a lot of the observations that have followed the more recent revelation that transmission within hospitals is uncommon,” says David VanInsberghe PhD ’19, a recent graduate of the MIT Department of Biology and lead author of the study. “Diarrheal events can trigger long-term Clostridium difficile colonization with recurrent blooms” in Nature Microbiology, published on Feb. 10.

The researchers analyzed human gut microbiome time series studies conducted on individuals who had diarrhea illnesses and were not treated with antibiotics. Observing the colonization of C. difficile soon after the illnesses were acquired, they tested this association directly by feeding mice increasing quantities of laxatives while exposing them to non-pathogenic C. difficile spores. Their results suggest that GI disturbances create a window of susceptibility to C. difficile colonization during recovery.

Further, the researchers found that carriers shed C. difficile in highly variable amounts day-to-day; the number of C. difficile cells shed in a carrier’s stool can increase by over 1,000 times in one day. These recurrent blooms likely influence the transmissibility of C. difficile outside of hospitals, and their unpredictability questions the reliability of single time-point diagnostics for detecting carriers.

“In our study, two of the people we followed with high temporal resolution became carriers outside of the hospital,” says VanInsberghe, who is now a postdoc in the Department of Pathology at Emory University. “The observations we made from their data helped us understand how people become susceptible to colonization and what the short- and long-term patterns in C. difficile abundance in carriers look like. Those patterns told us a lot about how C. difficile can spread between people outside of hospitals.”

“I believe that there is a lot of rethinking of C. diff infections at the moment and I hope our study will help contribute to ultimately better manage the risks associated with it,” says Martin Polz, senior author of the study and a visiting professor in MIT’s Parsons Laboratory for Environmental Science and Engineering within the MIT Department of Civil and Environmental Engineering.

The research team also included Joseph A. Elsherbini, a graduate student in the MIT Department of Biology; Bernard Varian, a researcher in MIT’s Division of Comparative Medicine; Theofilos Poutahidis, a professor in the Department of Pathology within the College of Veterinary Medicine at Aristotle University in Greece; and Susan Erdman, a principal research scientist in MIT’s Division of Comparative Medicine.

Gerald Fink awarded the Genetic Society of America’s Thomas Hunt Morgan Medal

Award recognizes scientists for lifetime achievement in genetics research who has a strong history as a mentor.

Merrill Meadow | Whitehead Institute
February 10, 2020

Gerald R. Fink, Whitehead Institute founding member and former director and professor of molecular genetics in the MIT Department of Biology, has been awarded the 2020 Thomas Hunt Morgan Medal, bestowed by the Genetics Society of America (GSA). The award recognizes a distinguished scientist who has a lifetime achievement in the field of genetics and a strong history as a mentor to fellow geneticists. The GSA is an international community of more than 5,000 scientists who advance the field of genetics.

Fink, who is also the Herman and Margaret Sokol Professor at Whitehead Institute, is a former GSA president and the 1982 recipient of the GSA Medal. In honoring him with the Thomas Hunt Morgan Medal, GSA is recognizing Fink’s discovery of principles central to genome organization and regulation in eukaryotic cells.

This year, the Morgan Medal will also be awarded to David Botstein, chief scientific officer for Calico Labs and professor emeritus of molecular biology at the Lewis-Sigler Institute for Integrative Genomics at Princeton University, in recognition of his multiple contributions to genetics, including the collaborative development of methods for defining genetic pathways, mapping genomes, and analyzing gene expression.

“These awards to Gerry and David are richly deserved and I am so pleased they are being honored together,” says Whitehead Institute Director David Page. “Gerry Fink has fundamentally changed the way researchers approach biological problems, and his many discoveries have significantly shaped modern science. David Botstein has helped drive modern genetics, establishing the ground rules for human genetic mapping.” Page has worked closely with both men: beginning his research career as an investigator in Botstein’s lab, and collaborating with Fink for more than three decades at Whitehead Institute.

The medals will be formally presented to Fink and Botstein at the Allied Genetics Conference in April.

Singing for joy and service

After surgery to correct childhood hearing loss, Swarna Jeewajee discovered a a desire to be a physician-scientist, and a love of a cappella music.

Shafaq Patel | MIT News correspondent
February 3, 2020

Swarna Jeewajee grew up loving music — she sings in the shower and blasts music that transports her to a happy state. But until this past year, she never felt confident singing outside her bedroom.

Now, the senior chemistry and biology major spends her Saturdays singing around the greater Boston area, at hospitals, homes for the elderly, and rehabilitation centers, with the a cappella group she co-founded, Singing For Service.

Jeewajee says she would not have been able to sing in front of people without the newfound confidence that came after she had transformative ear surgery in the spring of 2018.

Jeewajee grew up in Mauritius, a small island off the east coast of Madagascar, where she loved the water and going swimming. When she was around 8 years old, she developed chronic ear infections as a result of a cholesteatoma, which caused abnormal skin growth in her middle ear.

It took five years and three surgeries for the doctors in Mauritius to diagnose what had happened to Jeewajee’s ear. She spent some of her formative years at the hospital instead of leading a normal childhood and swimming at the beach.

By the time Jeewajee was properly diagnosed and treated, she was told her hearing could not be salvaged, and she had to wear a hearing aid.

“I sort of just accepted that this was my reality,” she says. “People used to ask me what the hearing aid was like — it was like hearing from headphones. It felt unnatural. But it wasn’t super hard to get used to it. I had to adapt to it.”

Eventually, the hearing aid became a part of Jeewajee, and she thought everything was fine. During her first year at MIT, she joined Concourse, a first-year learning community which offers smaller classes to fulfill MIT’s General Institute Requirements, but during her sophomore year, she enrolled in larger lecture classes. She found that she wasn’t able to hear as well, and it was a problem.

“When I was in high school, I didn’t look at my hearing disability as a disadvantage. But coming here and being in bigger lectures, I had to acknowledge that I was missing out on information,” Jeewajee says.

Over the winter break of her sophomore year, her mother, who had been living in the U.S. while Jeewajee was raised by her grandmother in Mauritius, convinced Jeewajee to see a specialist at Massachusetts Eye and Ear Hospital. That’s when Jeewajee encountered her role model, Felipe Santos, a surgeon who specializes in her hearing disorder.

Jeewajee had sought Santos’ help to find a higher-performing hearing aid, but instead he recommended a titanium implant to restore her hearing via a minimally invasive surgery. Now, Jeewajee does not require a hearing aid at all, and she can hear equally well from both ears.

“The surgery helped me with everything. I used to not be able to balance, and now I am better at that. I had no idea that my hearing affected that,” she says.

These changes, she says, are little things. But it’s the little things that made a large impact.

“I gained a lot more confidence after the surgery. In class, I was more comfortable raising my hand. Overall, I felt like I was living better,” she says.

This feeling is what brought Jeewajee to audition for the a cappella group. She never had any formal training in singing, but in January, during MIT’s Independent Activities Period, her friend mentioned that she wanted to start an a cappella group and convinced Jeewajee to help her launch Singing For Service.

Jeewajee describes Singing For Service as her “fun activity” at MIT, where she can just let loose. She is a soprano singer, and the group of nine to 12 students practices for about three hours a week before their weekly performances. They prepare three songs for each show; a typical lineup is a Disney melody, Josh Groban’s “You Raise Me Up,” and a mashup from the movie “The Greatest Showman.”

Her favorite part is when they take song requests from the audience. For example, Singing For Service recently went to a home for patients with multiple sclerosis, who requested songs from the Beatles and “Bohemian Rhapsody.” After the performance, the group mingles with the audience, which is one of Jeewajee’s favorite parts of the day.

She loves talking with patients and the elderly. Because Jeewajee was a patient for so many years growing up, she now wants to help people who are going through that type of experience. That is why she is going into the medical field and strives to earn an MD-PhD.

“When I was younger, I kind of always was at the doctor’s office. Doctors want to help you and give you a treatment and make you feel better. This aspect of medicine has always fascinated me, how someone is literally dedicating their time to helping you. They don’t know you, they’re not family, but they’re here for you. And I want to be there for someone as well,” she says.

Jeewajee says that because she grew up with a medical condition that was poorly understood, she wants to devote her career to search for answers to tough medical problems. Perhaps not surprisingly, she has gravitated toward cancer research.

She discovered her passion for this field after her first year at MIT, when she spent the summer conducting research in a cancer hospital in Lyon, through MISTI-France. There, she experienced an “epiphany” as she watched scientists and physicians come together to fight cancer, and was inspired to do the same.

She cites the hospital’s motto, “Chercher et soigner jusqu’à la guérison,” which means “Research and treat until the cure,” as an expression of what she will aspire to as a physician-scientist.

Last summer, while working at The Rockefeller University investigating mechanisms of resistance to cancer therapy, she developed a deeper appreciation for how individual patients can respond differently to a particular treatment, which is part of what makes cancer so hard to treat. Upon her return at MIT, she joined the Hemann lab at the Koch Institute for Integrative Cancer Research, where she conducts research on near-haploid leukemia, a subtype of blood cancer. Her ultimate goal is to find a vulnerability that may be exploited to develop new treatments for these patients.

The Koch Institute has become her second home on MIT’s campus. She enjoys the company of her labmates, who she says are good mentors and equally passionate about science. The walls of the lab are adorned with science-related memes and cartoons, and amusing photos of the team’s scientific adventures.

Jeewajee says her work at the Koch Institute has reaffirmed her motivation to pursue a career combining science and medicine.

“I want to be working on something that is challenging so that I can truly make a difference. Even if I am working with patients for whom we may or may not have the right treatment, I want to have the capacity to be there for them and help them understand and navigate the situation, like doctors did for me growing up,” Jeewajee says.

Maurice Fox, professor emeritus of biology, dies at 95

A caring mentor and staunch political activist, Fox cared deeply about his students, the department, and the scientific enterprise.

Raleigh McElvery | Department of Biology
February 1, 2020

Maurice Sanford Fox, professor emeritus of biology and former head of the Department of Biology, passed away on Jan. 26 at the age of 95.

Fox was instrumental in creating and revising several courses within the biology major, and served as department head from 1985 to 1989. His research focused on bacterial genetics, and he pioneered investigations into bacterial transformation.

“Maury was a force in the department for many years,” says current department head Alan Grossman, the Praecis Professor of Biology. “He was very involved in the graduate program, and served as a mentor and friend to many of us. He cared deeply about the department, the scientific enterprise, and bioethics.”

Fox was born in the Bronx, New York, in 1924 to a family of poor Jewish immigrants; his father had fled Russia to avoid being conscripted into the tsar’s army. Growing up, Fox had little interest in science, and considered himself small for his age and “not very noticeable.” However, one teacher took an interest in him, and encouraged him to apply to Stuyvesant High School, which specialized in math and science. It took him an hour to make the commute each day, but he relished his biology and chemistry courses, where he got to study flies and flatworms and learn how to blow glass.

Fox graduated from high school at age 16 and enrolled in Queens College with the intent of majoring in chemistry. After a year and a half, he left to enlist in the U.S. Army Air Force and attend their meteorology program, eventually becoming a full-time meteorologist and traveling all over the American South to forecast weather for the military. At the time, he aspired to become a doctor, but didn’t have enough money for medical school. Instead, at age 22, he returned to Queens College to continue taking chemistry courses.

He went on to receive his PhD in chemistry from the University of Chicago, where he studied under Willard Libby and specialized in nuclear chemistry. Realizing he had no interest in nuclear weapons, Fox began scanning the bulletin boards at the University of Chicago for other opportunities post-graduation, and came across Leo Szilard’s lab. Szilard had discovered a chemical reaction, known as the “Szilard-Chalmers reaction,” which Fox had just used to complete his thesis in physical chemistry. Fox joined the lab and became fascinated with Szilard’s continuous-flow device, called a chemostat, used for growing hundreds of generations of bacteria under constant conditions. To Fox, the device was a new way to think about kinetics, which “treated living things like chemicals.”

Fox considered Szilard to be his most influential mentor, inspiring him both scientifically and personally. Szilard encouraged Fox to take biology classes, and Fox became increasingly enthralled by bacterial genetics — a subject he later taught in classes of his own.

Several years later, the two joined forces to establish the Council for a Livable World. Their plan was to create an organization that would raise money for senatorial candidates who would be “sensible” about nuclear weapons and avoid nuclear catastrophe. Fox felt this conviction to uphold the social and political responsibilities of being a researcher throughout his entire life. He fought to reduce the risks of radiation, biological warfare, and gene editing, and later went on to chair MIT’s Radiation Protection Committee and become a member of UNESCO’s International Bioethics Committee.

At the time that Fox and Szilard were building the Council for a Livable World, Fox was completing his postdoc with biochemist Rollin Hotchkiss at Rockefeller Institute for Medical Research — the country’s first biomedical institute — which later became Rockefeller University. After his postdoc, he rose through the ranks to become an associate professor before being recruited to MIT in 1962.

As a bacterial geneticist, Fox used bacterial transformation as an experimental model for genetic analysis to gain insights into mechanisms of genetic modification. He later extended his investigations to transduction and conjugation. Fox helped lay the foundation of our modern understanding of DNA mutation, recombination, and mismatch repair — efforts which directly and indirectly influenced key advancements like the search for RNA viruses and the discovery of the SOS response. He also had a keen interest in evaluating the effectiveness of medical procedures, including diagnosis and treatment of breast cancer. He was a member of the American Academy of Arts and Sciences, the National Academy of Sciences, and the National Academy of Medicine, among other prominent professional organizations.

Fox remained active in the Department of Biology for 34 years, retiring in 1996. During that time, he taught several Course 7 subjects and mentored graduate and undergraduate students, as well as postdocs.

Fox was among the founding generation of molecular biologists who migrated from the physical sciences, says David Botstein, one of Fox’s earliest trainees at MIT. He remembers Fox as both an intellectual mentor and a life coach. Fox befriended many and his house was always full of visitors, with whom he shared his love for science, culture, art, and politics. “Maury introduced me to the quantitative study of microorganisms and the importance of DNA mutation and recombination — which I had expected — but also to the rigorous and persistent skepticism that led me to constantly search for alternatives to the current thinking,” Botstein says. “In this way, Maury introduced me to an approach to science and learning that shaped my entire career.”

Michael Lichten PhD ’82 also credits Fox with teaching him how to think about science. “Maury taught as much by example as by direction, and he transmitted a deep and profound commitment to teaching that guides many of his students to this day,” he says.

“Maury was a colleague, a mentor, and, most importantly, a friend,” recalls H. Robert Horvitz, Nobel laureate and one of Fox’s former undergraduate students. “Maury truly helped shaped my life, from my undergraduate days as a student in his genetics class to many more recent days, when he always offered both warmth and wisdom.”

“This is a man who made an astonishing difference in an astonishing number of lives,” adds Evelyn Fox Keller, Fox’s sister and professor emerita of history and philosophy of science at MIT. “He made a difference to the world. His life was devoted to making the world a better place for people — and he did.”

Fox is survived by his three sons, Jonathan, Gregory, and Michael, and his sisters Evelyn and Frances, who is a professor emerita of political science at the Graduate Center, City University of New York. Fox was predeceased by his wife of more than 50 years, Sally. The Department of Biology will hold a memorial celebration of Fox’s life in the spring.