Author: mantulin

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

Raleigh McElvery | Department of Biology

May 13, 2020

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

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

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

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

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

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

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

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

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

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

Sandi Miller | Department of Mathematics

May 8, 2020

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

Kerry Emanuel

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

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

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

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

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

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

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

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

David Sabatini

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

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

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

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

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

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

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

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

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

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

Peter Shor

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

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

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

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

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

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

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

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

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

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

Postdoc Izabella Pena uses social media to combat the infodemic about the Covid-19 pandemic.

Fernanda Ferreira | School of Science

May 4, 2020

In mid-March, Izabella Pena received a WhatsApp text from a friend in Indianapolis, Indiana. “He said, ‘Oh, I got your audio message from a priest in rural São Paulo,’” remembers Pena, a postdoc in Department of Biology Professor David Sabatini’s lab at the Whitehead Institute for Biomedical Research.

Pena had recorded the five-minute audio message about risk groups and the novel coronavirus SARS-CoV-2 for her family’s text thread after she heard one-too-many comments about how only the elderly caught the more severe forms of Covid-19. She never imagined it would spread like wildfire. “I realized the power of these tools,” says Pena of WhatsApp. “You can really reach people and share your information.”

While Pena’s message was fact-checked and scientifically correct, a lot of the information being shared on these platforms isn’t. In Pena’s native Brazil, the messaging platform WhatsApp has played an outsized role in the spread of fake news concerning SARS-CoV-2. Seeing the onslaught of misinformation, Pena first panicked. Then she fought back, choosing to use the vehicles of fake news to spread facts. “We scientists need to learn how to use WhatsApp, YouTube, and Twitter to communicate,” says Pena. “Because that’s how people are getting their information.”

At first, Pena’s misinformation-busting efforts were focused on friends and family. She recorded short audio messages in Portuguese to answer their questions and try to convince them that Covid-19 isn’t just another cold. The rapid spread of her audio messages, which alerted listeners about the importance of physical isolation and risk groups, sparked an idea: to take her science communication efforts from WhatsApp to YouTube, where she could reach a larger audience. Video also has the benefit of being a visual medium, where there’s a face attached to the information being shared. “I think that if people see you, there’s more reliability,” says Pena.

Pena uploaded her first video in late March, answering questions she had received via WhatsApp about Covid-19. Since then, she’s uploaded another five videos and is aiming to release one a week while the pandemic lasts. Many of these videos are in direct response to the messages she gets from viewers. “For example, everybody is asking when is life going to go back to normal, and I think life is only going to go back to ‘normal’ when there’s a vaccine,” says Pena. On April 10, she uploaded a video focused on vaccines, explaining what exactly a vaccine is and how they are made.

On camera, Pena is warm and inviting, delivering updated information about the coronavirus’s biology and epidemiology without clunky jargon and with an abundance of analogies. In a recent video that delved into the biology of SARS-CoV-2 and the different treatments being explored for the virus, she compared the human protein TMPRSS2, which primes the virus’ spike protein to enable the fusion of the virion to a cell’s membrane, to the scissors you use to open a tough plastic snack bag.

In using analogies, Pena is following the advice of Paulo Freire, a famed Brazilian educator and one of her personal idols. “Freire says that the best way to teach something very complicated to someone is to try to bring that concept close to their lives,” says Pena.

Trying to make complex and novel science digestible requires time. According to Pena, just writing the script and developing the analogies takes a couple of hours. “I collect all the information I need before I write the script,” says Pena, whose videos include a long list of references in the description, an unexpected sight on YouTube. “Then I film and edit the video. It all takes a few hours.”

Pena’s videos are filmed late at night because she continues to perform research during the pandemic, mostly virtually. But, she explains, “I’m part of the essential personnel in my lab.” Pena’s work in the Sabatini Lab focuses on the lysosome, the garbage disposal unit of cells that breaks down old cell parts and waste to recycle nutrients. It’s the perfect organelle for someone who has always enjoyed cell metabolism.

“I’ve always liked how chemicals in the cells are made and broken down,” says Pena. Her PhD research at the University of Campinas in Brazil investigated how metabolic problems in the brain could cause epilepsy. Since joining the Sabatini lab in 2018, Pena studies neurodegenerative disorders, like Parkinson’s and Huntington’s, and what role the lysosome plays in them. “For neurodegenerative diseases, there’s a lot of evidence that there’s lysosome influence,” she says. “There are many lysosome gene mutations associated to these disorders, so it’s a nice target to look at.”

Mostly working from home in Cambridge, Massachusetts, Pena is analyzing data and writing grants and papers, balancing her research with her “after-hours job” as a science communicator. “It’s a lot of commitment and dedication, but I believe this is very important, so I’ll keep doing it,” she says. “We are living a hard time, where science and education are constantly under attack. As scientists, we need to help inform people with accurate and life-saving information”.

Recently, Pena added another job title to her resumé: vice-president of ContraCovid, an initiative to make coronavirus information accessible to Latino and immigrant individuals. “We are sharing information in four languages: English, Portuguese, Spanish, and Haitian Creole, to benefit the community here in the U.S. and abroad,” says Pena. But ContraCovid wants to do more, including creating videos like Pena’s in other languages and recruiting more scientists, so that their materials can reach more and more people.

Accessibility of information is at the front of Pena’s mind when she sits down to make a new video. “If you look at how scientists communicate with each other, it’s a bit intimidating,” says Pena. The jargon and the excess of data make it hard for the general public to locate the main takeaways. Pena focuses on stripping away the excess and delivering the message, such as the importance of flattening the curve, in an easily digestible manner.

When imagining her viewers, Pena thinks of her mother. “My mom is not a scientist, but she’s super into technology like YouTube and WhatsApp,” says Pena, who usually sends her audio clips and videos to her mom first, only uploading them once her mom gives the go-ahead. “My mom helps a lot with sharing the videos because she has lots of followers,” Pena laughs. That’s actually how her involvement in Covid-19 outreach started: with her mom wildly sharing Pena’s audio message about risk groups with her numerous followers.

Microneedles made of silk-based material can target plant tissues for delivery of micronutrients, hormones, or genes.

David L. Chandler | MIT News Office

April 27, 2020

While the human world is reeling from one pandemic, there are several ongoing epidemics that affect crops and put global food production at risk. Oranges, olives, and bananas are already under threat in many areas due to diseases that affect plants’ circulatory systems and that cannot be treated by applying pesticides.

A new method developed by engineers at MIT may offer a starting point for delivering life-saving treatments to plants ravaged by such diseases.

These diseases are difficult to detect early and to treat, given the lack of precision tools to access plant vasculature to treat pathogens and to sample biomarkers. The MIT team decided to take some of the principles involved in precision medicine for humans and adapt them to develop plant-specific biomaterials and drug-delivery devices.

The method uses an array of microneedles made of a silk-based biomaterial to deliver nutrients, drugs, or other molecules to specific parts of the plant. The findings are described in the journal Advanced Science, in a paper by MIT professors Benedetto Marelli and Jing-Ke-Weng, graduate student Yunteng Cao, postdoc Eugene Lim at MIT, and postdoc Menglong Xu at the Whitehead Institute for Biomedical Research.

The microneedles, which the researchers call phytoinjectors, can be made in a variety of sizes and shapes, and can deliver material specifically to a plant’s roots, stems, or leaves, or into its xylem (the vascular tissue involved in water transportation from roots to canopy) or phloem (the vascular tissue that circulates metabolites throughout the plant). In lab tests, the team used tomato and tobacco plants, but the system could be adapted to almost any crop, they say. The microneedles can not only deliver targeted payloads of molecules into the plant, but they can also be used to take samples from the plants for lab analysis.

The work started in response to a request from the U.S. Department of Agriculture for ideas on how to address the citrus greening crisis, which is threatening the collapse of a $9 billion industry, Marelli says. The disease is spread by an insect called the Asian citrus psyllid that carries a bacterium into the plant. There is as yet no cure for it, and millions of acres of U.S. orchards have already been devastated. In response, Marelli’s lab swung into gear to develop the novel microneedle technology, led by Cao as his thesis project.

The disease infects the phloem of the whole plant, including roots, which are very difficult to reach with any conventional treatment, Marelli explains. Most pesticides are simply sprayed or painted onto a plant’s leaves or stems, and little if any penetrates to the root system. Such treatments may appear to work for a short while, but then the bacteria bounce back and do their damage. What is needed is something that can target the phloem circulating through a plant’s tissues, which could carry an antibacterial compound down into the roots. That’s just what some version of the new microneedles could potentially accomplish, he says.

“We wanted to solve the technical problem of how you can have a precise access to the plant vasculature,” Cao adds. This would allow researchers to inject pesticides, for example, that would be transported between the root system and the leaves. Present approaches use “needles that are very large and very invasive, and that results in damaging the plant,” he says. To find a substitute, they built on previous work that had produced microneedles using silk-based material for injecting human vaccines.

“We found that adaptations of a material designed for drug delivery in humans to plants was not straightforward, due to differences not only in tissue vasculature, but also in fluid composition,” Lim says. The microneedles designed for human use were intended to biodegrade naturally in the body’s moisture, but plants have far less available water, so the material didn’t dissolve and was not useful for delivering the pesticide or other macromolecules into the phloem. The researchers had to design a new material, but they decided to stick with silk as its basis. That’s because of silk’s strength, its inertness in plants (preventing undesirable side effects), and the fact that it degrades into tiny particles that don’t risk clogging the plant’s internal vasculature systems.

They used biotechnology tools to increase silk’s hydrophilicity (making it attract water), while keeping the material strong enough to penetrate the plant’s epidermis and degradable enough to then get out of the way.

Sure enough, they tested the material on their lab tomato and tobacco plants, and were able to observe injected materials, in this case fluorescent molecules, moving all they way through the plant, from roots to leaves.

“We think this is a new tool that can be used by plant biologists and bioengineers to better understand transport phenomena in plants,” Cao says. In addition, it can be used “to deliver payloads into plants, and this can solve several problems. For example, you can think about delivering micronutrients, or you can think about delivering genes, to change the gene expression of the plant or to basically engineer a plant.”

“Now, the interests of the lab for the phytoinjectors have expanded beyond antibiotic delivery to genetic engineering and point-of-care diagnostics,” Lim adds.

For example, in their experiments with tobacco plants, they were able to inject an organism called Agrobacterium to alter the plant’s DNA – a typical bioengineering tool, but delivered in a new and precise way.

So far, this is a lab technique using precision equipment, so in its present form it would not be useful for agricultural-scale applications, but the hope is that it can be used, for example, to bioengineer disease-resistant varieties of important crop plants. The team has also done tests using a modified toy dart gun mounted to a small drone, which was able to fire microneedles into plants in the field. Ultimately, such a process might be automated using autonomous vehicles, Marelli says, for agricultural-scale use.

Meanwhile, the team continues to work on adapting the system to the varied needs and conditions of different kinds of plants and their tissues. “There’s a lot of variation among them, really,” Marelli says, so you need to think about having devices that are plant-specific. For the future, our research interests will go beyond antibiotic delivery to genetic engineering and point-of-care diagnostics based on metabolite sampling.”

The work was supported by the Office of Naval Research, the National Science Foundation, and the Keck Foundation.

Three MIT undergraduates who use computer science to explore human biology and health honored for their academic achievements.

Fernanda Ferreira | School of Science

April 10, 2020

MIT students Katie Collins, Vaishnavi Phadnis, and Vaibhavi Shah have  been selected to receive a Barry Goldwater Scholarship for the 2020-21 academic year. Over 5,000 college students from across the United States were nominated for the scholarships, from which only 396 recipients were selected based on academic merit.

The Goldwater scholarships have been conferred since 1989 by the Barry Goldwater Scholarship and Excellence in Education Foundation. These scholarships have supported undergraduates who go on to become leading scientists, engineers, and mathematicians in their respective fields. All of the 2020-21 Goldwater Scholars intend to obtain a doctorate in their area of research, including the three MIT recipients.

Katie Collins, a third-year majoring in brain and cognitive sciences with minors in computer science and biomedical engineering, got involved with research in high school, when she worked on computational models of metabolic networks and synthetic gene networks in the lab of Department of Electrical Engineering and Computer Science Professor Timothy Lu at MIT. It was this project that led her to realize how challenging it is to model and analyze complex biological networks. She also learned that machine learning can provide a path for exploring these networks and understanding human diseases. This realization has coursed a scientific path for Collins that is equally steeped in computer science and human biology.

Over the past few years, Collins has become increasingly interested in the human brain, particularly what machine learning can learn from human common-sense reasoning and the way brains process sparse, noisy data. “I aim to develop novel computational algorithms to analyze complex, high-dimensional data in biomedicine, as well as advance modelling paradigms to improve our understanding of human cognition,” explains Collins. In his letter of recommendation, Professor Tomaso Poggio, the Eugene McDermott Professor in the Department of Brain and Cognitive Sciences and one of Collins’ mentors, wrote, “It is very difficult to imagine a better candidate for the Goldwater fellowship.” Collins plans to pursue a PhD studying machine learning or computational neuroscience and to one day run her own lab. “I hope to become a professor, leading a research program at the interface of computer science and cognitive neuroscience.”

Vaishnavi Phadnis, a second-year majoring in computer science and molecular biology, sees molecular and cellular biology as the bridge between chemistry and life, and she’s been enthralled with understanding that bridge since 7th grade, when she learned about the chemical basis of the cell. Phadnis spent two years working in a cancer research lab while still in high school, an experience which convinced her that research was not just her passion but also her future. “In my first week at MIT, I approached Professor Robert Weinberg, and I’ve been grateful to do research in his lab ever since,” she says.

“Vaishnavi’s exuberance makes her a joy to have in the lab,” wrote Weinberg, who is the Daniel Ludwig Professor in the Department of Biology. Phadnis is investigating ferroptosis, a recently discovered, iron-dependent form of cell death that may be relevant in neurodegeneration and also a potential strategy for targeting highly aggressive cancer cells. “She is a phenomenon who has vastly exceeded our expectations of the powers of someone her age,” Weinberg says. Phadnis is thankful to Weinberg and all the scientific mentors, both past and present, that have inspired her along her research path. Deciphering the mechanisms behind fundamental cellular processes and exploring their application in human diseases is something Phadnis plans to continue doing in her future as a physician-scientist after pursuing an MD/PhD. “I hope to devote most of my time to leading my own research group, while also practicing medicine,” she says.

Vaibhavi Shah, a third-year studying biological engineering with a minor in science, technology and society, spent a lot of time in high school theorizing ways to tackle major shortcomings in medicine and science with the help of technology. “When I came to college, I was able to bring some of these ideas to fruition,” she says, working with both the Big Data in Radiology Group at the University of California at San Francisco and the lab of Professor Mriganka Sur, the Newton Professor of Neuroscience in the Department of Brain and Cognitive Sciences.

Shah is particularly interested in integrating innovative research findings with traditional clinical practices. According to her, technology, like computer vision algorithms, can be adopted to diagnose diseases such as Alzheimer’s, allowing patients to start appropriate treatments earlier. “This is often harder to do at smaller, rural institutions that may not always have a specialist present,” says Shah, and algorithms can help fill that gap. One of aims of Shah’s research is to improve the efficiency and equitability of physician decision-making. “My ultimate goal is to improve patient outcomes, and I aim to do this by tackling emerging scientific questions in machine learning and artificial intelligence at the forefront of neurology,” she says. The clinic is a place Shah expects to be in the future after obtaining her physician-scientist training, saying, “I hope to a practicing neurosurgeon and clinical investigator.”

The Barry Goldwater Scholarship and Excellence in Education Program was established by Congress in 1986 to honor Senator Barry Goldwater, a soldier and statesman who served the country for 56 years. Awardees receive scholarships of up to $7,500 a year to cover costs related to tuition, room and board, fees, and books.

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.