Mentorship and medicine

MIT senior Daniel Zhang aims to provide hope for young patients and support to young students.

Celina Zhao | Department of Biology
February 24, 2022

During the virtual spring 2020 semester, Daniel Zhang, a senior majoring in biology, put his time at home to good use. In the garage of his home in San Diego, California, Zhang helped his 13-year-old brother build a lab to study dry eye disease.

This combination of mentorship and medicine feels like second nature to Zhang. When his parents opened a family-run optometry clinic, Zhang was their first patient and then their receptionist. And after a close family member passed away from leukemia, he remembers thinking, “Humans are susceptible to so many diseases — why don’t we have better cures?”

That question propelled him to spend his high school summers studying biomarkers for the early detection of leukemia at the University of California at San Diego. He was invited to present his research at the London International Youth Science Forum, where he spoke to scientists from almost 70 countries. Afterward, he was hooked on the idea of scientific research as a career.

“Research is like standing on the shoulders of giants,” he says. “My experience at the forum was when I knew I loved science and wanted to continue using it to find common ground with others from completely different cultures and backgrounds.”

Exploring the forefront of cancer research

As soon as he arrived at MIT as a first-year undergraduate, Zhang began working under the guidance of postdoc Peter Westcott in professor Tyler Jacks’ lab. The lab focuses on developing better mouse and organoid models to study cancer progression — in Zhang’s case, metastatic colorectal cancer.

One of the ways to model colorectal cancer is by injecting an engineered virus directly into the colons of mice. The viruses, called lentiviral agents, “knock out” tumor suppressor genes and activate the so-called oncogenes that drive cancer forward. However, the imprecise nature of this injection also unintentionally transforms many “off-target” cells into cancer cells, producing a cancer that’s far too widespread and aggressive. Additionally, rare tumors called sarcomas are often initiated rather than adenocarcinomas, the type of tumor found in 95 percent of human cases. As a result, these mouse models are limited in their ability to accurately model colorectal cancer.

To address this problem, Zhang and Westcott designed a method using CRISPR/Cas9 to target a special stem cell called LGR5+, which researchers believe are the types of cells that, when mutated, grow into colorectal cancer. His technique modifies only the LGR5+ cells, which would allow researchers to control the rate at which adenocarcinomas grow. Therefore, it generates a model that is not only much more similar to human colorectal cancer than other models, but also allows researchers to quickly test for other potential cancer driver genes with CRISPR/Cas9. Designing an accurate model is crucial for developing and testing effective new therapies for patients, Zhang says.

During MIT’s virtual spring and fall semesters of 2020, Zhang shifted his focus from benchwork in the lab to computational biology. Using patient data from the Cancer Genome Atlas, Zhang analyzed mutation rates and discovered three genes potentially involved in colorectal cancer tumor suppression. He plans to test their function in his new mouse model to further validate how the dysfunction of these genes drives colorectal cancer progression.

For his work on organoid modeling of colorectal cancer, a third project he’s worked on during his time at the Jacks lab, he also won recognition from the American Association for Cancer Research (AACR). As one of 10 winners of the Undergraduate Scholar Award, he had the opportunity to present his research at the virtual AACR conference in 2021 and again at the next AACR Conference in New Orleans in April 2022.

He credits MIT’s “mens et manus” philosophy, encouraging the hands-on application of knowledge, as a large part of his early success in research.

“I’ve found that, at MIT, a lot of people are pursuing projects and asking questions that have never been thought of before,” Zhang says. “No one has ever been able to develop a late-stage model for colorectal cancer that’s amenable to gene editing. As far as I know, other than us, no one in the world is even working on this.”

Inspiring future generations to pursue STEM

Outside of the lab, Zhang devotes a substantial amount of time to sharing the science he’s so passionate about. Not only has he been awarded the Gene Brown Prize for undergraduate teaching for his time as a teaching assistant for the lab class 7.002 (Fundamentals of Experimental Molecular Biology), but he’s also taken on leadership roles in science outreach activities.

During the 2020-21 academic year, he served as co-director of DynaMIT, an outreach program that organizes a two-week STEM program over the summer for underserved sixth to ninth graders in the greater Boston area. Although the program is traditionally held in-person, in summer 2021 it was held virtually. But Zhang and the rest of the board didn’t let the virtual format deter them from maximizing the fun and interactive nature of the program. They packed and shipped nearly 120 science kits focused on five major topics — astronomy, biology, chemistry, mechanical engineering, and math — allowing the students to explore everything from paper rockets to catapults and trebuchets to homemade ice cream.

“At first, we were worried that most of the students wouldn’t turn on their cameras, since we saw that trend all over MIT classes during the semester,” Zhang says. “But almost everyone had their cameras on the entire time. It was really gratifying to see students come in on Monday really shy, but by Friday be actively participating, making jokes with the mentors, and being really excited about STEM.”

To investigate the long-term impacts of the program, he also helped kick-start a project that followed up with DynaMIT alumni, some of whom have already graduated from college. Zhang says: “We were happy to see that 80-90 percent of DynaMIT alumni enjoyed the program, rating it four or five out of five, and close to 70 percent of them said that DynaMIT had a really positive impact on their trajectory toward a career in STEM.”

Zhang has also served as president of the MIT Pre-medical Society, with the goals of fostering an encouraging environment for premed undergraduates, and providing guidance and resources to first- and second-year students still undecided about the premed path. To achieve these objectives, he pioneered an MIT-hosted mixer with the premedical societies of other Boston colleges, including Wellesley College, Boston University, Tufts University, and Harvard University. At the mixer, students were able to network with each other and listen to guest speakers from the different universities talk about their experiences in medicine. He also started a “big/little” initiative that paired third- and fourth-year mentors with first- and second-year students.

Providing new opportunity and hope

The wealth of activities Zhang has participated in at MIT has inspired his choices for the future. After graduation, he plans to take a gap year and work as a research technician in pediatric oncology before applying to MD/PhD programs.

On the mentorship side, he’s currently working to establish a nonprofit organization called Future African Scientist with his former Ugandan roommate, Martin Lubowa, whom he met at a study abroad program during MIT’s Independent Activities Period in 2020. The organization will teach high schoolers in Africa professional skills and expose them to different STEM topics — a project Zhang plans to work on post-MIT and into the long term.

Ultimately, he hopes to lead his own lab at the intersection of CRISPR-Cas9 technology and cancer biology, and to serve as a mentor to future generations of researchers and physicians.

As he puts it: “All of the experiences I’ve had so far have solidified my goal of conducting research that impacts patients, especially young ones. Being able to provide new opportunity and hope to patients suffering from late-stage metastatic diseases with no current cures is what inspires me every day.”

Alan Grossman to step down as head of the Department of Biology

Grossman led the biology community for eight years, increasing faculty diversity, support for outreach programs and graduate students.

School of Science
February 23, 2022

Alan D. Grossman, the Praecis Professor of Biology at MIT, has announced he will step down as the head of the Department of Biology before the start of the next academic year. He will continue to lead the department until the new head is selected. A search committee will convene later this spring to recommend candidates for Grossman’s successor.

“Alan Grossman is an outstanding biologist who is, and has been, deeply committed to the research and educational missions of the biology department,” says Nergis Mavalvala, the Curtis and Kathleen Marble Professor of Astrophysics and the dean of the MIT School of Science. “He has time and again established MIT biology as a leader in the life sciences at the Institute, in Kendall Square, and beyond.”

“It has been a privilege to lead this department and its talented members — faculty, staff, and students — for the past eight years,” says Grossman. “With the dedication and drive of this community, we have accomplished so much together and set new and ambitious goals for the future of life sciences research and education.”

Grossman was instrumental in securing a $50 million gift from Professor Emeritus Paul Schimmel PhD ’66 and his family to support life sciences across the Institute. Schimmel’s initial gift of $25 million established the Schimmel Family Program for Life Sciences that matched $25 million secured from other sources in support of the Department of Biology. The remaining $25 million from the Schimmel family will support the Schimmel Family Program in the form of matching funds.

“This transformative gift provides students with the resources they need to be successful in their education, research, and careers,” says Institute Professor Phillip A. Sharp, who also contributed to the matching gift. “Alan’s leadership and vision provided the framework to make this gift a reality for graduate students who perform life sciences research across the Institute, not just in biology.”

For many years, Grossman was deeply involved in graduate education. He served on the committees that oversee the graduate program in biology and the interdepartmental graduate program in computational and systems biology. For seven years, Grossman was director or co-director of the biology graduate program. He helped establish the interdepartmental graduate program in microbiology in 2007 and served as its founding director until 2012.

Before assuming the role as department head, Grossman also served the department as associate head and had served MIT on several committees, including as a member of the Committee on Curriculum and the Faculty Advisory Committee for the Office of Minority Education. Through the work of the department’s academic officers, student leaders, and advisors, Grossman oversaw the development of the most recent interdisciplinary undergraduate biology major, Course 5-7 (Chemistry and Biology).

Within his department, Grossman raised funds to endow support for students in the MIT Summer Research Program in Biology (MSRP-Biology). He worked with others to expand the diversity of the graduate program, the applicant pool for biology faculty positions, and the scientific workforce through a variety of outreach programs and endeavors.

Recently, Grossman raised additional funds to endow MSRP-Biology. Michael Gould and Sara Moss supplemented their initial gift in 2015 with an additional donation to further support, endow and rename MSRP-Biology to the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology to honor Gould’s parents.

“Sara and I are grateful for Alan’s nurturing of the program,” said Gould. “Without Alan, we never would have supported this wonderful program; and with Alan at the helm and Mandana Sassanfar as the director of outreach, we knew that many talented individuals would benefit from the research opportunities at MIT.”

Grossman’s tenure also saw the establishment of a cryo-electron microscopy (cryo-EM) facility at MIT. An anonymous donation of $5 million and a $2.5 million gift from the Arnold and Mabel Beckman Foundation supported the purchase of two cryo-electron microscopes that are housed in MIT.nano. These microscopes are used by life science researchers from many departments across MIT and throughout the Boston area.

“The existence of this facility has made it possible for MIT to recruit outstanding junior faculty members focused on using cryo-EM to address fundamental biological problems,” says associate department head Professor Jacqueline Lees. “At a more general level, Alan has been remarkably successful at junior faculty recruitment and in increasing the diversity of our faculty.”

During Grossman’s tenure as department head and in collaboration with the MIT-affiliated life sciences institutes and the hard work of search committees, the department has hired more than 20 faculty members, over than half of whom are women and/or from groups underrepresented in STEM. This faculty renewal involved forging a relationship with the Ragon Institute of MGH, MIT, and Harvard and includes three new faculty members located at the Ragon Institute. With the influx of new faculty members, the department’s senior faculty instituted a robust plan for mentoring junior faculty, supplementing programs that are offered at the school and Institute levels.

In his own research, Grossman combines a range of approaches — genetic, molecular, physiological, biochemical, cell-biological, and genomic — to study fundamental biological processes in bacteria. His current work is focused mechanisms controlling horizontal gene transfer, the process by which bacteria move genes from one organism to another, the primary means by which antibiotic resistances are spread among bacteria.

Grossman received a BA in biochemistry from Brown University in 1979, and a PhD in molecular biology from the University of Wisconsin at Madison in 1984. After a postdoctoral fellowship in the Department of Cellular and Developmental Biology at Harvard University, Grossman joined MIT’s Department of Biology in 1988. He is a fellow of the American Academy of Arts and Sciences, the American Academy of Microbiology, and is a member of the National Academy of Sciences. He received a life-saving heart transplant in 2006.

Seven new faculty join the MIT School of Science

Departments of Biology and Brain and Cognitive Sciences welcome new professors.

School of Science
February 16, 2022

This winter, seven new faculty members join the MIT School of Science in the departments of Biology and Brain and Cognitive Sciences.

Siniša Hrvatin studies how animals initiate, regulate, and survive states of stasis, such as torpor and hibernation. To survive extreme environments, many animals have evolved the ability to decrease metabolic rate and body temperature and enter dormant states. His long-term goal is to harness the potential of these biological adaptations to advance medicine. Previously, he identified the neurons that regulate mouse torpor and established a platform for the development of cell-type-specific viral drivers.

Hrvatin earned his bachelor’s degree in biochemical sciences in 2007 and his PhD in stem cell and regenerative medicine in 2013, both from Harvard University. He was then a postdoc in bioengineering at MIT and a postdoc in neurobiology at Harvard Medical School. Hrvatin returns to MIT as an assistant professor of biology and a member of the Whitehead Institute for Biomedical Research.

Sara Prescott investigates how sensory inputs from within the body control mammalian physiology and behavior. Specifically, she uses mammalian airways as a model system to explore how the cells that line the surface of the body communicate with parts of the nervous system. For example, what mechanisms elicit a reflexive cough? Prescott’s research considers the critical questions of how airway insults are detected, encoded, and adapted to mammalian airways with the ultimate goal of providing new ways to treat autonomic dysfunction.

Prescott earned her bachelor’s degree in molecular biology from Princeton University in 2008 followed by her PhD in developmental biology from Stanford University in 2016. Prior to joining MIT, she was a postdoc at Harvard Medical School and Howard Hughes Medical Institute. The Department of Biology welcomes Prescott as an assistant professor.

Alison Ringel is a T-cell immunologist with a background in biochemistry, biophysics, and structural biology. She investigates how environmental factors such as aging, metabolism, and diet impact tumor progress and the immune responses that cause tumor control. By mapping the environment around a tumor on a cellular level, she seeks to gain a molecular understanding of cancer risk factors.

Ringel received a bachelor’s degree in molecular biology, biochemistry, and physics from Wesleyan University, then a PhD in molecular biophysics from John Hopkins University School of Medicine. Previously, Ringel was a postdoc in the Department of Cell Biology at Harvard Medical School. She joins MIT as an assistant professor in the Department of Biology and a core member of the Ragon Institute of MGH, MIT and Harvard.

Francisco J. Sánchez-Rivera PhD ’16 investigates genetic variation with a focus on cancer. He integrates genome engineering technologies, genetically-engineered mouse models (GEMMs), and single cell lineage tracing and omics approaches in order to understand the mechanics of cancer development and evolution. With state-of-the-art technologies — including a CRISPR-based genome editing system he developed as a graduate student at MIT — he hopes to make discoveries in cancer genetics that will shed light on disease progression and pave the way for better therapeutic treatments.

Sánchez-Rivera received his bachelor’s degree in microbiology from the University of Puerto Rico at Mayagüez followed by a PhD in biology from MIT. He then pursued postdoctoral studies at Memorial Sloan Kettering Cancer Center supported by a HHMI Hanna Gray Fellowship. Sánchez-Rivera returns to MIT as an assistant professor in the Department of Biology and a member of the Koch Institute for Integrative Cancer Research at MIT.

Nidhi Seethapathi builds predictive models to help understand human movement with a combination of theory, computational modeling, and experiments. Her research focuses on understanding the objectives that govern movement decisions, the strategies used to execute movement, and how new movements are learned. By studying movement in real-world contexts using creative approaches, Seethapathi aims to make discoveries and develop tools that could improve neuromotor rehabilitation.

Seethapathi earned her bachelor’s degree in mechanical engineering from the Veermata Jijabai Technological Institute followed by her PhD in mechanical engineering from Ohio State University. In 2018, she continued to the University of Pennsylvania where she was a postdoc. She joins MIT as an assistant professor in the Department of Brain and Cognitive Sciences with a shared appointment in the Department of Electrical Engineering and Computer Science at the MIT Schwarzman College of Computing.

Hernandez Moura Silva researches how the immune system supports tissue physiology. Silva focuses on macrophages, a type of immune cell involved in tissue homeostasis. He plans to establish new strategies to explore the effects and mechanisms of such immune-related pathways, his research ultimately leading to the development of therapeutic approaches to treat human diseases.

Silva earned a bachelor’s degree in biological sciences and a master’s degree in molecular biology from the University of Brasilia. He continued to complete a PhD in immunology at the University of São Paulo School of Medicine: Heart Institute. Most recently, he acted as the Bernard Levine Postdoctoral Fellow in immunology and immuno-metabolism at the New York University School of Medicine: Skirball Institute of Biomolecular Medicine. Silva joins MIT as an assistant professor in the Department of Biology and a core member of the Ragon Institute.

Yadira Soto-Feliciano PhD ’16 studies chromatin — the complex of DNA and proteins that make up chromosomes. She combines cancer biology and epigenetics to understand how certain proteins affect gene expression and, in turn, how they impact the development of cancer and other diseases. In decoding the chemical language of chromatin, Soto-Feliciano pursues a basic understanding of gene regulation that could improve the clinical management of diseases associated with their dysfunction.

Soto-Feliciano received her bachelor’s degree in chemistry from the University of Puerto Rico at Mayagüez followed by a PhD in biology from MIT, where she was also a research fellow with the Koch Institute. Most recently, she was the Damon Runyon-Sohn Pediatric Cancer Postdoctoral Fellow at The Rockefeller University. Soto-Feliciano returns to MIT as an assistant professor in the Department of Biology and a member of the Koch Institute.

Probing how proteins pair up inside cells

MIT biologists drilled down into how proteins recognize and bind to one another, informing drug treatments for cancer.

Raleigh McElvery | Department of Biology
February 3, 2022

Despite its minute size, a single cell contains billions of molecules that bustle around and bind to one another, carrying out vital functions. The human genome encodes about 20,000 proteins, most of which interact with partner proteins to mediate upwards of 400,000 distinct interactions. These partners don’t just latch onto one another haphazardly; they only bind to very specific companions that they must recognize inside the crowded cell. If they create the wrong pairings — or even the right pairings at the wrong place or wrong time — cancer or other diseases can ensue. Scientists are hard at work investigating these protein-protein relationships, in order to understand how they work, and potentially create drugs that disrupt or mimic them to treat disease.

The average human protein is composed of approximately 400 building blocks called amino acids, which are strung together and folded into a complex 3D structure. Within this long string of building blocks, some proteins contain stretches of four to six amino acids called short linear motifs (SLiMs), which mediate protein-protein interactions. Despite their simplicity and small size, SLiMs and their binding partners facilitate key cellular processes. However, it’s been historically difficult to devise experiments to probe how SLiMs recognize their specific binding partners.

To address this problem, a group led by Theresa Hwang PhD ’21 designed a screening method to understand how SLiMs selectively bind to certain proteins, and even distinguish between those with similar structures. Using the detailed information they gleaned from studying these interactions, the researchers created their own synthetic molecule capable of binding extremely tightly to a protein called ENAH, which is implicated in cancer metastasis. The team shared their findings in a pair of eLife studies, one published on Dec. 2, 2021, and the other published Jan. 25.

“The ability to test hundreds of thousands of potential SLiMs for binding provides a powerful tool to explore why proteins prefer specific SLiM partners over others,” says Amy Keating, professor of biology and biological engineering and the senior author on both studies. “As we gain an understanding of the tricks that a protein uses to select its partners, we can apply these in protein design to make our own binders to modulate protein function for research or therapeutic purposes.”

Most existing screens for SLiMs simply select for short, tight binders, while neglecting SLiMs that don’t grip their partner proteins quite as strongly. To survey SLiMs with a wide range of binding affinities, Keating, Hwang, and their colleagues developed their own screen called MassTitr.

The researchers also suspected that the amino acids on either side of the SLiM’s core four-to-six amino acid sequence might play an underappreciated role in binding. To test their theory, they used MassTitr to screen the human proteome in longer chunks comprised of 36 amino acids, in order to see which “extended” SLiMs would associate with the protein ENAH.

ENAH, sometimes referred to as Mena, helps cells to move. This ability to migrate is critical for healthy cells, but cancer cells can co-opt it to spread. Scientists have found that reducing the amount of ENAH decreases the cancer cell’s ability to invade other tissues — suggesting that formulating drugs to disrupt this protein and its interactions could treat cancer.

Thanks to MassTitr, the team identified 33 SLiM-containing proteins that bound to ENAH — 19 of which are potentially novel binding partners. They also discovered three distinct patterns of amino acids flanking core SLiM sequences that helped the SLiMs bind even tighter to ENAH. Of these extended SLiMs, one found in a protein called PCARE bound to ENAH with the highest known affinity of any SLiM to date.

Next, the researchers combined a computer program called dTERMen with X-ray crystallography in order understand how and why PCARE binds to ENAH over ENAH’s two nearly identical sister proteins (VASP and EVL). Hwang and her colleagues saw that the amino acids flanking PCARE’s core SliM caused ENAH to change shape slightly when the two made contact, allowing the binding sites to latch onto one another. VASP and EVL, by contrast, could not undergo this structural change, so the PCARE SliM did not bind to either of them as tightly.

Inspired by this unique interaction, Hwang designed her own protein that bound to ENAH with unprecedented affinity and specificity. “It was exciting that we were able to come up with such a specific binder,” she says. “This work lays the foundation for designing synthetic molecules with the potential to disrupt protein-protein interactions that cause disease — or to help scientists learn more about ENAH and other SLiM-binding proteins.”

Ylva Ivarsson, a professor of biochemistry at Uppsala University who was not involved with the study, says that understanding how proteins find their binding partners is a question of fundamental importance to cell function and regulation. The two eLife studies, she explains, show that extended SLiMs play an underappreciated role in determining the affinity and specificity of these binding interactions.

“The studies shed light on the idea that context matters, and provide a screening strategy for a variety of context-dependent binding interactions,” she says. “Hwang and co-authors have created valuable tools for dissecting the cellular function of proteins and their binding partners. Their approach could even inspire ENAH-specific inhibitors for therapeutic purposes.”

Hwang’s biggest takeaway from the project is that things are not always as they seem: even short, simple protein segments can play complex roles in the cell. As she puts it: “We should really appreciate SLiMs more.”

School of Science announces 2022 Infinite Expansion Awards

Eight postdocs and research scientists within the School of Science honored for contributions to the Institute.

School of Science
January 28, 2022

The MIT School of Science has announced eight postdocs and research scientists as recipients of the 2022 Infinite Expansion Award.

The award, formerly known as the Infinite Kilometer Award, was created in 2012 to highlight extraordinary members of the MIT science community. The awardees are nominated not only for their research, but for going above and beyond in mentoring junior colleagues, participating in educational programs, and contributing to their departments, labs, and research centers, the school, and the Institute.

The 2022 School of Science Infinite Expansion winners are:

  • Héctor de Jesús-Cortés, a postdoc in the Picower Institute for Learning and Memory, nominated by professor and Department of Brain and Cognitive Sciences (BCS) head Michale Fee, professor and McGovern Institute for Brain Research Director Robert Desimone, professor and Picower Institute Director Li-Huei Tsai, professor and associate BCS head Laura Schulz, associate professor and associate BCS head Joshua McDermott, and professor and BCS Postdoc Officer Mark Bear for his “awe-inspiring commitment of time and energy to research, outreach, education, mentorship, and community;”
  • Harold Erbin, a postdoc in the Laboratory for Nuclear Science’s Institute for Artificial Intelligence and Fundamental Interactions (IAIFI), nominated by professor and IAIFI Director Jesse Thaler, associate professor and IAIFI Deputy Director Mike Williams, and associate professor and IAIFI Early Career and Equity Committee Chair Tracy Slatyer for “provid[ing] exemplary service on the IAIFI Early Career and Equity Committee” and being “actively involved in many other IAIFI community building efforts;”
  • Megan Hill, a postdoc in the Department of Chemistry, nominated by Professor Jeremiah Johnson for being an “outstanding scientist” who has “also made exceptional contributions to our community through her mentorship activities and participation in Women in Chemistry;”
  • Kevin Kuns, a postdoc in the Kavli Institute for Astrophysics and Space Research, nominated by Associate Professor Matthew Evans for “consistently go[ing] beyond expectations;”
  • Xingcheng Lin, a postdoc in the Department of Chemistry, nominated by Associate Professor Bin Zhang for being “very talented, extremely hardworking, and genuinely enthusiastic about science;”
  • Alexandra Pike, a postdoc in the Department of Biology, nominated by Professor Stephen Bell for “not only excel[ing] in the laboratory” but also being “an exemplary citizen in the biology department, contributing to teaching, community, and to improving diversity, equity, and inclusion in the department;”
  • Nora Shipp, a postdoc with the Kavli Institute for Astrophysics and Space Research, nominated by Assistant Professor Lina Necib for being “independent, efficient, with great leadership qualities” with “impeccable” research; and
  • Jakob Voigts, a research scientist in the McGovern Institute for Brain Research, nominated by Associate Professor Mark Harnett and his laboratory for “contribut[ing] to the growth and development of the lab and its members in numerous and irreplaceable ways.”

Winners are honored with a monetary award and will be celebrated with family, friends, and nominators at a later date, along with recipients of the Infinite Mile Award.

3 Questions: Kristin Knouse on the liver’s regenerative capabilities

The clinically-trained cell biologist exploits the liver’s unique capacities in search of new medical applications.

Grace van Deelen | Department of Biology
December 15, 2021

Why is the liver the only human organ that can regenerate? How does it know when it’s been injured? What can our understanding of the liver contribute to regenerative medicine? These are just some of the questions that new assistant professor of biology Kristin Knouse and her lab members are asking in their research at the Koch Institute for Integrative Cancer Research. Knouse sat down to discuss why the liver is so unique, what lessons we might learn from the organ, and what its regeneration might teach us about cancer.

Q: Your lab is interested in questions about how body tissues sense and respond to damage. What is it about the liver that makes it a good tool to model those questions?

A: I’ve always felt that we, as scientists, have so much to gain from treasuring nature’s exceptions, because those exceptions can shine light onto a completely unknown area of biology and provide building blocks to confer such novelty to other systems. When it comes to organ regeneration in mammals, the liver is that exception. It is the only solid organ that can completely regenerate itself. You can damage or remove over 75 percent of the liver and the organ will completely regenerate in a matter of weeks. The liver therefore contains the instructions for how to regenerate a solid organ; however, we have yet to access and interpret those instructions. If we could fully understand how the liver is able to regenerate itself, perhaps one day we could coax other solid organs to do the same.

There are some things we already know about liver regeneration, such as when it begins, what genes are expressed, and how long it takes. However, we still don’t understand why the liver can regenerate but other organs cannot. Why is it that these fully differentiated liver cells — cells that have already assumed specialized roles in the liver — can re-enter the cell cycle and regenerate the organ? We don’t have a molecular explanation for this. Our lab is working to answer this fundamental question of cell and organ biology and apply our discoveries to unlock new approaches for regenerative medicine. In this regard, I don’t necessarily consider myself exclusively a liver biologist, but rather someone who is leveraging the liver to address this much broader biological problem.

Q: As an MD/PhD student, you conducted your graduate research in the lab of the late Professor Angelika Amon here at MIT. How did your work in her lab lead to an interest in studying the liver’s regenerative capacities?

A: What was incredible about being in Angelika’s lab was that she had an interest in almost everything and gave me tremendous independence in what I pursued. I began my graduate research in her lab with an interest in cell division, and I was doing experiments to observe how cells from different mammalian tissues divide. I was isolating cells from different mouse tissues and then studying them in culture. In doing that, I found that when the cells were isolated and grown in a dish they could not segregate their chromosomes properly, suggesting that the tissue environment was essential for accurate cell division. In order to further study and compare these two different contexts — cells in a tissue versus cells in culture — I was keen to study a tissue in which I could observe a lot of cells undergoing cell division at the same time.

So I thought back to my time in medical school, and I remembered that the liver has the ability to completely regenerate itself. With a single surgery to remove part of the liver, I could stimulate millions of cells to divide. I therefore began exploiting liver regeneration as a means of studying chromosome segregation in tissue. But as I continued to perform surgeries on mice and watch the liver rapidly regenerate itself, I couldn’t help but become absolutely fascinated by this exceptional biological process. It was that fascination with this incredibly unique but poorly understood phenomenon — alongside the realization that there was a huge, unmet medical need in the area of regeneration — that convinced me to dedicate my career to studying this.

Q: What kinds of clinical applications might a better understanding of organ regeneration lead to, and what role do you see your lab playing in that research?

A: The most proximal medical application for our work is to confer regenerative capacity to organs that are currently non-regenerative. As we begin to achieve a molecular understanding of how and why the liver can regenerate, we put ourselves in a powerful position to identify and surmount the barriers to regeneration in non-regenerative tissues, such as the heart and nervous system. By answering these complementary questions, we bring ourselves closer to the possibility that, one day, if someone has a heart attack or a spinal cord injury, we could deliver a therapy that stimulates the tissue to regenerate itself. I realize that may sound like a moonshot now, but I don’t think any problem is insurmountable so long as it can be broken down into a series of tractable questions.

Beyond regenerative medicine, I believe our work studying liver regeneration also has implications for cancer. At first glance this may seem counterintuitive, as rapid regrowth is the exact opposite of what we want cancer cells to do. However, the reality is that the majority of cancer-related deaths are attributable not to the rapidly proliferating cells that constitute primary tumors, but rather to the cells that disperse from the primary tumor and lie dormant for years before manifesting as metastatic disease and creating another tumor. These dormant cells evade most of the cancer therapies designed to target rapidly proliferating cells. If you think about it, these dormant cells are not unlike the liver: they are quiet for months, maybe years, and then suddenly awaken. I hope that as we start to understand more about the liver, we might learn how to target these dormant cancer cells, prevent metastatic disease, and thereby offer lasting cancer cures.

MIT Future Founders Initiative announces prize competition to promote female entrepreneurs in biotech

Nine MIT researchers selected as finalists for 2021 prize supported by Northpond Ventures; grand prize winner to receive $250K toward commercializing her human health-related invention.

Kate S. Petersen | School of Engineering
November 30, 2021

In a fitting sequel to its entrepreneurship “boot camp” educational lecture series last fall, the MIT Future Founders Initiative has announced the MIT Future Founders Prize Competition, supported by Northpond Ventures, and named the MIT faculty cohort that will participate in this year’s competition. The Future Founders Initiative was established in 2020 to promote female entrepreneurship in biotech.

Despite increasing representation at MIT, female science and engineering faculty found biotech startups at a disproportionately low rate compared with their male colleagues, according to research led by the initiative’s founders, MIT Professor Sangeeta Bhatia, MIT Professor and President Emerita Susan Hockfield, and MIT Amgen Professor of Biology Emerita Nancy Hopkins. In addition to highlighting systemic gender imbalances in the biotech pipeline, the initiative’s founders emphasize that the dearth of female biotech entrepreneurs represents lost opportunities for society as a whole — a bottleneck in the proliferation of publicly accessible medical and technological innovation.

“A very common myth is that representation of women in the pipeline is getting better with time … We can now look at the data … and simply say, ‘that’s not true’,” said Bhatia, who is the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, in an interview for the March/April 2021 MIT Faculty Newsletter. “We need new solutions. This isn’t just about waiting and being optimistic.”

Inspired by generous funding from Northpond Labs, the research and development-focused affiliate of Northpond Ventures, and by the success of other MIT prize incentive competitions such as the Climate Tech and Energy Prize, the Future Founders Initiative Prize Competition will be structured as a learning cohort in which participants will be supported in commercializing their existing inventions with instruction in market assessments, fundraising, and business capitalization, as well as other programming. The program, which is being run as a partnership between the MIT School of Engineering and the Martin Trust Center for MIT Entrepreneurship, provides hands-on opportunities to learn from industry leaders about their experiences, ranging from licensing technology to creating early startup companies. Bhatia and Kit Hickey, an entrepreneur-in-residence at the Martin Trust Center and senior lecturer at the MIT Sloan School of Management, are co-directors of the program.

“The competition is an extraordinary effort to increase the number of female faculty who translate their research and ideas into real-world applications through entrepreneurship,” says Anantha Chandrakasan, dean of the MIT School of Engineering and Vannevar Bush Professor of Electrical Engineering and Computer Science. “Our hope is that this likewise serves as an opportunity for participants to gain exposure and experience to the many ways in which they could achieve commercial impact through their research.”

At the end of the program, the cohort members will pitch their ideas to a selection committee composed of MIT faculty, biotech founders, and venture capitalists. The grand prize winner will receive $250,000 in discretionary funds, and two runners-up will receive $100,000. The winners will be announced at a showcase event, at which the entire cohort will present their work. All participants will also receive a $10,000 stipend for participating in the competition.

“The biggest payoff is not identifying the winner of the competition,” says Bhatia. “Really, what we are doing is creating a cohort … and then, at the end, we want to create a lot of visibility for these women and make them ‘top of mind’ in the community.”

The Selection Committee members for the MIT Future Founders Prize Competition are:

  • Bill Aulet, professor of the practice in the MIT Sloan School of Management and managing director of the Martin Trust Center for MIT Entrepreneurship
  • Sangeeta Bhatia, the John and Dorothy Wilson Professor of Electrical Engineering and Computer Science at MIT; a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science; and founder of Hepregen, Glympse Bio, and Satellite Bio
  • Kit Hickey, senior lecturer in the MIT Sloan School of Management and entrepreneur-in-residence at the Martin Trust Center
  • Susan Hockfield, MIT president emerita and professor of neuroscience
  • Andrea Jackson, director at Northpond Ventures
  • Harvey Lodish, professor of biology and biomedical engineering at MIT and founder of Genzyme, Millennium, and Rubius
  • Fiona Murray, associate dean for innovation and inclusion in the MIT Sloan School of Management; the William Porter Professor of Entrepreneurship; co-director of the MIT Innovation Initiative; and faculty director of the MIT Legatum Center
  • Amy Schulman, founding CEO of Lyndra Therapeutics and partner at Polaris Partners
  • Nandita Shangari, managing director at Novartis Venture Fund

“As an investment firm dedicated to supporting entrepreneurs, we are acutely aware of the limited number of companies founded and led by women in academia. We believe humanity should be benefiting from brilliant ideas and scientific breakthroughs from women in science, which could address many of the world’s most pressing problems. Together with MIT, we are providing an opportunity for women faculty members to enhance their visibility and gain access to the venture capital ecosystem,” says Andrea Jackson, director at Northpond Ventures.

“This first cohort is representative of the unrealized opportunity this program is designed to capture. While it will take a while to build a robust community of connections and role models, I am pleased and confident this program will make entrepreneurship more accessible and inclusive to our community, which will greatly benefit society,” says Susan Hockfield, MIT president emerita.

The MIT Future Founders Prize Competition cohort members were selected from schools across MIT, including the School of Science, the School of Engineering, and Media Lab within the School of Architecture and Planning. They are:

Polina Anikeeva is professor of materials science and engineering and brain and cognitive sciences, an associate member of the McGovern Institute for Brain Research, and the associate director of the Research Laboratory of Electronics. She is particularly interested in advancing the possibility of future neuroprosthetics, through biologically-informed materials synthesis, modeling, and device fabrication. Anikeeva earned her BS in biophysics from St. Petersburg State Polytechnic University and her PhD in materials science and engineering from MIT.

Natalie Artzi is principal research scientist in the Institute of Medical Engineering and Science and an assistant professor in the department of medicine at Brigham and Women’s Hospital. Through the development of smart materials and medical devices, her research seeks to “personalize” medical interventions based on the specific presentation of diseased tissue in a given patient. She earned both her BS and PhD in chemical engineering from the Technion-Israel Institute of Technology.

Laurie A. Boyer is professor of biology and biological engineering in the Department of Biology. By studying how diverse molecular programs cross-talk to regulate the developing heart, she seeks to develop new therapies that can help repair cardiac tissue. She earned her BS in biomedical science from Framingham State University and her PhD from the University of Massachusetts Medical School.

Tal Cohen is associate professor in the departments of Civil and Environmental Engineering and Mechanical Engineering. She wields her understanding of how materials behave when they are pushed to their extremes to tackle engineering challenges in medicine and industry. She earned her BS, MS, and PhD in aerospace engineering from the Technion-Israel Institute of Technology.

Canan Dagdeviren is assistant professor of media arts and sciences and the LG Career Development Professor of Media Arts and Sciences. Her research focus is on creating new sensing, energy harvesting, and actuation devices that can be stretched, wrapped, folded, twisted, and implanted onto the human body while maintaining optimal performance. She earned her BS in physics engineering from Hacettepe University, her MS in materials science and engineering from Sabanci University, and her PhD in materials science and engineering from the University of Illinois at Urbana-Champaign.

Ariel Furst is the Raymond (1921) & Helen St. Laurent Career Development Professor in the Department of Chemical Engineering. Her research addresses challenges in global health and sustainability, utilizing electrochemical methods and biomaterials engineering. She is particularly interested in new technologies that detect and treat disease. Furst earned her BS in chemistry at the University of Chicago and her PhD at Caltech.

Kristin Knouse is assistant professor in the Department of Biology and the Koch Institute for Integrative Cancer Research. She develops tools to investigate the molecular regulation of organ injury and regeneration directly within a living organism with the goal of uncovering novel therapeutic avenues for diverse diseases. She earned her BS in biology from Duke University, her PhD and MD through the Harvard and MIT MD-PhD program.

Elly Nedivi is the William R. (1964) & Linda R. Young Professor of Neuroscience at the Picower Institute for Learning and Memory with joint appointments in the departments of Brain and Cognitive Sciences and Biology. Through her research of neurons, genes, and proteins, Nedivi focuses on elucidating the cellular mechanisms that control plasticity in both the developing and adult brain. She earned her BS in biology from Hebrew University and her PhD in neuroscience from Stanford University.

Ellen Roche is associate professor in the Department of Mechanical Engineering and Institute of Medical Engineering and Science, and the W.M. Keck Career Development Professor in Biomedical Engineering. Borrowing principles and design forms she observes in nature, Roche works to develop implantable therapeutic devices that assist cardiac and other biological function. She earned her bachelor’s degree in biomedical engineering from the National University of Ireland at Galway, her MS in bioengineering from Trinity College Dublin, and her PhD from Harvard University.

Investigating pathogens and their life cycles, for the benefit of society

Senior Desmond Edwards has an insatiable curiosity about how the human body works — and how diseases stop it from working.

Leah Campbell | School of Science
November 21, 2021

Desmond Edwards was a little kid when first learned about typhoid fever. Fortunately, he didn’t have the disease. He was looking at a cartoon public health announcement. The cartoon, produced by the Pan American Health Organization, was designed to educate people in his home country of Jamaica about the importance of immunizations for diseases like typhoid. The typhoid character in the cartoon was so unpleasant it gave him nightmares.

Edwards did have his fair share of hospital visits throughout his childhood. But, his own struggles with infection and illness, and those typhoid cartoon nightmares, became his inspiration for pursuing a career studying human disease. At age 6, Edwards was running impromptu baking soda experiments in repurposed glitter containers in his kitchen. Today, he is a senior at MIT, majoring in biology and biological engineering, thanks to a team of dedicated mentors and an insatiable curiosity about how the human body works — or, more accurately, how diseases stop it from working.

Finding a way into research

Edwards knew he wanted to do research but says he assumed that that was something you did after you got your degree. Imagine his surprise, then, upon arriving at MIT in 2018 and meeting classmates who not only had done research, but already had publications. Realizing that he could get a jump-start on his career, he sought out research opportunities and enrolled in the biology class 7.102 (Introduction to Molecular Biology Techniques) for his first-year Independent Activities Period. The class was specifically geared toward first-year students like him with no lab experience.

“It was a great first look at how research is done,” Edwards says of the class. Students took water samples from the Charles River and were expected to identify the strains of bacteria found in those samples using various biological techniques. They looked at the bacteria under a microscope. They examined how the samples metabolized different sources of carbon and determined if they could be stained by different dyes. They even got to try out basic genetic sequencing. “We knew where we were starting. And we knew the end goal,” says Edwards. The in-between was up to them.

Class 7.102 is taught by Mandana Sassanfar, a lecturer in biology and the department’s director of diversity and science outreach. For Sassanfar, the class is also an opportunity to find lab placements for students. In Edwards’ case, she literally led him to the lab of Assistant Professor Becky Lamason, walking up with him one evening to meet a postdoc, Jon McGinn, to talk about the lab and opportunities there. After Edwards expressed his interest to Lamason, she responded within 30 minutes. McGinn even followed up to answer any lingering questions.

“I think that was really what pushed it over the edge,” he says of his decision to take a position in the Lamason lab. “I saw that they were interested not only in having me as someone to help them do research, but also interested in my personal development.”

At the edges of cells and disciplines

The Lamason lab researches the life cycle of two different pathogens, trying to understand how the bacteria move between cells. Edwards has focused on Rickettsia parkeri, a tick-borne pathogen that’s responsible for causing spotted fever. This type of Rickettsia is what biologists call an obligate intracellular pathogen, meaning that it resides within cells and can only survive when it’s in a host. “I like to call it a glorified virus,” Edwards jokes.

Edwards gets excited describing the various ways in which R. parkeri can outsmart its infected host. It’s evolved to escape the phagosome of the cell, the small liquid sac that forms from the cell membrane and engulfs organisms like bacteria that pose a threat. Once it gets past the phagosome and enters the cell, it takes over cellular machinery, just like a virus. At this point of the life cycle, a bacterium will typically replicate so many times that the infected cell will burst, and the pathogen will spread widely. R. parkeri, though, can also spread to uninfected cells directly through the membrane where two cells touch. By not causing a cell to burst, the bacterium can spread without alerting the host to its presence.

“From a disease standpoint, that’s extremely interesting,” says Edwards. “If you’re not leaving the cell or being detected, you don’t see antibodies. You don’t see immune cells. It’s very hard to get that standard immune response.”

In his time in the lab, Edwards has worked on various projects related to Rickettsia, including developing genetic tools to study the pathogen and examining the potential genes that might be important in its life cycle. His projects sit at the intersection of biology and biological engineering.

“For me, I kind of live in between those spaces,” Edwards explains. “I am extremely interested in understanding the mechanisms that underlie all of biology. But I don’t only want to understand those systems. I also want to engineer them and apply them in ways that can be beneficial to society.”

Science for society

Last year, Edwards won the Whitehead Prize from the Department of Biology, recognizing students with “outstanding promise for a career in biological research.” But his extracurricular activities have been driven more by his desire to apply science for tangible social benefits.

“How do you take the science that you’ve done in the lab, in different research contexts, and translate that in a way that the public will actually benefit from it?” he asks.

Science education is particularly important for Edwards, given the educational opportunities he was given to help get to MIT. As a high schooler, Edwards participated in a Caribbean Science Foundation initiative called the Student Programme for Innovation in Science and Engineering. SPISE, as it’s known, is designed to encourage and support Caribbean students interested in careers in STEM fields. The program is modeled on the Minority Introduction to Engineering and Science program (MITES) at MIT. Cardinal Warde, a professor of electrical engineering, is himself from the Caribbean and serves as the faculty director for both MITES and SPISE.

“That experience not only kind of opened my eyes a bit more to what was available, what was in the realm of possibilities, but also provided support to get to MIT,” Edwards says of SPISE. For example, the program helped with college applications and worked with him to secure an internship at a biotech company when he first moved to the United States.

“If education falters, then you don’t replenish the field of science,” Edwards argues. “You don’t get younger generations excited, and the public won’t care.”

Edwards has also taken a leadership role in the MIT Biotechnology Group, a campus-wide student group meant to build connections between the MIT community and thought leaders in industry, business, and academia. For Edwards, the biotech and pharmaceutical industries play a clear role in disease treatment, and he knew he wanted to join the group before he even arrived at MIT. In 2019, he became co-director of the Biotech Group’s Industry Initiative, a program focused on preparing members for industry careers. In 2020, he became undergraduate president, and this year he’s co-president of the entire organization. Edwards speaks proudly of what the Biotech Group has accomplished during his tenure on the executive board, highlighting that they not only have the largest cohort ever this year, but it’s also the first time the group has been majority undergraduate.

Somehow, in between his research and outreach work, Edwards finds time to minor in French, play for the Quidditch team, and serve as co-president on the Course 20 Undergraduate Board, among other activities. It’s a balancing act that Edwards has mastered over his time at MIT because of his genuine excitement and interest in everything that he does.

“I don’t like not understanding things,” he jokes. “That applies to science, but it also extends to people.”

A stealthy way to combat tumors

MIT biologists show that helper immune cells disguised as cancer cells can help rejuvenate T cells that attack tumors.

Anne Trafton | MIT News Office
November 18, 2021

Under the right circumstances, the body’s T cells can detect and destroy cancer cells. However, in most cancer patients, T cells become disarmed once they enter the environment surrounding a tumor.

Scientists are now trying to find ways to help treat patients by jumpstarting those lackluster T cells. Much of the research in this field, known as cancer immunotherapy, has focused on finding ways to stimulate those T cells directly. MIT researchers have now uncovered a possible new way to indirectly activate those T cells, by recruiting a population of helper immune cells called dendritic cells.

In a new study, the researchers identified a specific subset of dendritic cells that have a unique way of activating T cells. These dendritic cells can cloak themselves in tumor proteins, allowing them to impersonate cancer cells and trigger a strong T cell response.

“We knew that dendritic cells are incredibly important for the antitumor immune response, but we didn’t know what really constitutes the optimal dendritic cell response to a tumor,” says Stefani Spranger, the Howard S. and Linda B. Stern Career Development Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.

The results suggest that finding ways to stimulate that specific population of dendritic cells could help to enhance the effectiveness of cancer immunotherapy, she says. In a study of mice, the researchers showed that stimulating these dendritic cells slowed the growth of melanoma and colon tumors.

Spranger is the senior author of the study, which appears today in the journal Immunity. The lead author of the paper is MIT graduate student Ellen Duong.

Spontaneous regression

When tumors begin to form, they produce cancerous proteins that T cells recognize as foreign. This sometimes allows T cells to eliminate tumors before they get very large. In other cases, tumors are able to secrete chemical signals that deactivate T cells, allowing the tumors to continue growing unchecked.

Dendritic cells are known to help activate tumor-fighting T cells, but there are many different subtypes of dendritic cells, and their individual roles in T cell activation are not fully characterized. In this study, the MIT team wanted to investigate which types of dendritic cells are involved in T cell responses that successfully eliminate tumors.

To do that, they found a tumor cell line, from a type of muscle tumor, that has been shown to spontaneously regress in mice. Such cell lines are difficult to find because researchers usually don’t keep them around if they can’t form tumors, Spranger says.

Studying mice, they compared tumors produced by that regressive cell line with a type of colon carcinoma, which forms tumors that grow larger after being implanted in the body. The researchers found that in the progressing tumors, the T cell response quickly became exhausted, while in the regressing tumors, T cells remained functional.

The researchers then analyzed the dendritic cell populations that were present in each of these tumors. One of the main functions of dendritic cells is to take up debris from dying cells, such as cancer cells or cells infected with a pathogen, and then present the protein fragments to T cells, alerting them to the infection or tumor.

The best-known type of dendritic cells required for antitumor immunity  are DC1 cells, which interact with T cells that are able to eliminate cancer cells. However, the researchers found that DC1 cells were not needed for tumor regression. Instead, using single-cell RNA sequencing technology, they identified a previously unknown activation state of DC2 cells, a different type of dendritic cell, that was driving T cell activation in the regressing tumors.

The MIT team found that instead of ingesting cellular debris, these dendritic cells swipe proteins called MHC complexes from tumor cells and display them on their own surfaces. When T cells encounter these dendritic cells masquerading as tumor cells, the T cells become strongly activated and begin killing the tumor cells.

This specialized population of dendritic cells appears to be activated by type one interferon, a signaling molecule that cells usually produce in response to viral infection. The researchers found a small population of these dendritic cells in colon and melanoma tumors that progress, but they were not properly activated. However, if they treated those tumors with interferon, the dendritic cells began stimulating T cells to attack tumor cells.

Targeted therapy

Some types of interferon have been used to help treat cancer, but it can have widespread side effects when given systemically. The findings from this study suggest that it could be beneficial to deliver interferon in a very targeted way to tumor cells, or to use a drug that would provoke tumor cells to produce type I interferon, Spranger says.

The researchers now plan to investigate just how much type I interferon is needed to generate a strong T cell response. Most tumor cells produce a small amount of type I interferon but not enough to activate the dendritic cell population that invigorates T cells. On the other hand, too much interferon can be toxic to cells.

“Our immune system is hardwired to respond to nuanced differences in type I interferon very dramatically, and that is something that is intriguing from an immunological perspective,” Spranger says.

The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, a National Institutes of Health Pre-Doctoral Training Grant, a David H. Koch Graduate Fellowship, and the Pew-Steward Fellowship.

Studying learner engagement during the Covid-19 pandemic

Researchers analyze and compare pre- and post-pandemic data for introductory biology MOOC 7.00x.

Stefanie Koperniak | MIT Open Learning
November 17, 2021

While massive open online classes (MOOCs) have been a significant trend in higher education for many years now, they have gained a new level of attention during the Covid-19 pandemic. Open online courses became a critical resource for a wide audience of new learners during the first stages of the pandemic — including students whose academic programs had shifted online, teachers seeking online resources, and individuals suddenly facing lockdown or unemployment and looking to build new skills.

Mary Ellen Wiltrout, director of online and blended learning initiatives and lecturer in digital learning in the Department of Biology, and Virginia “Katie” Blackwell, currently an MIT PhD student in biology, published a paper this summer in the European MOOC Stakeholder Summit (EMOOCs 2021) conference proceedings evaluating data for the online course 7.00x (Introduction to Biology). Their research objective was to better understand whether the shift to online learning that occurred during the pandemic led to increased learner engagement in the course.

Blackwell participated in this research as part of the Bernard S. and Sophie G. Gould MIT Summer Research Program (MSRP) in Biology, during the uniquely remote MSRPx-Biology 2020 student cohort. She collaborated on the project while working toward her bachelor’s degree in biochemistry and molecular biology from the University of Texas at Dallas, and collaborated on the research while in Texas. She has since applied and been accepted into MIT’s PhD program in biology.

“MSRP Biology was a transformative experience for me. I learned a lot about the nature of research and the MIT community in a very short period of time and loved every second of the program. Without MSRP, I would never have even considered applying to MIT for my PhD. After MSRP and working with Mary Ellen, MIT biology became my first-choice program and I felt like I had a shot at getting in,” says Blackwell.

Many MOOC platforms experienced increased website traffic in 2020, with 30 new MOOC-based degrees and more than 60 million new learners.

“We find that the tremendous, lifelong learning opportunities that MOOCs provide are even more important and sought-after when traditional education is disrupted. During the pandemic, people had to be at home more often, and some faced unemployment requiring a career transition,” says Wiltrout.

Wiltrout and Blackwell wanted to build a deeper understanding of learner profiles rather than looking exclusively at enrollments. They looked at all available data, including: enrollment demographics (i.e., country and “.edu” participants); proportion of learners engaged with videos, problems, and forums; number of individual engagement events with videos, problems, and forums; verification and performance; and the course “track” level — including auditing (for free) and verified (paying and receiving access to additional course content, including access to a comprehensive competency exam). They analyzed data in these areas from five runs of 7.00x in this study, including three pre-pandemic runs of April, July, and November 2019 and two pandemic runs of March and July 2020.

The March 2020 run had the same count of verified-track participants as all three pre-pandemic runs combined. The July 2020 run enrolled nearly as many verified-track participants as the March 2020 run. Wiltrout says that introductory biology content may have attracted great attention during the early days and months of the Covid-19 pandemic, as people may have had a new (or renewed) interest in learning about (or reviewing) viruses, RNA, the inner workings of cells, and more.

Wiltrout and Blackwell found that the enrollment count for the March 2020 run of the course increased at almost triple the rate of the three pre-pandemic runs. During the early days of March 2020, the enrollment metrics appeared similar to enrollment metrics for the April 2019 run — both in rate and count — but the enrollment rate increased sharply around March 15, 2020. The July 2020 run began with more than twice as many learners already enrolled by the first day of the course, but continued with half the enrollment rate of the March 2020 course. In terms of learner demographics, during the pandemic, there was a higher proportion of learners with .edu addresses, indicating that MOOCs were often used by students enrolled in other schools.

Viewings of course videos increased at the beginning of the pandemic. During the March 2020 run, both verified-track and certified participants viewed far more unique videos during March 2020 than in the pre-pandemic runs of the course; even auditor-track learners — not aiming for certification — still viewed all videos offered. During the July 2020 run, however, both verified-track and certified participants viewed far fewer unique videos than during all prior runs. The proportion of participants who viewed at least one video decreased in the July 2020 run to 53 percent, from a mean of 64 percent in prior runs. Blackwell and Wiltrout say that this decrease — as well as the overall dip in participation in July 2020 — might be attributed to shifting circumstances for learners that allowed for less time to watch videos and participate in the course, as well as some fatigue from the extra screen time.

The study found that 4.4 percent of March 2020 participants and 4.5 percent of July 2020 participants engaged through forum posting — which was 1.4 to 3.3 times higher than pre-pandemic proportions of forum posting. The increase in forum engagement may point to a desire for community engagement during a time when many were isolated and sheltering in place.

“Through the day-to-day work of my research team and also through the engagement of the learners in 7.00x, we can see that there is great potential for meaningful connections in remote experiences,” says Wiltrout. “An increase in participation for an online course may not always remain at the same high level, in the long term, but overall, we’re continuing to see an increase in the number of MOOCs and other online programs offered by all universities and institutions, as well as an increase in online learners.”