Placement: Promote to Homepage

Lessons from teaching about the pandemic in real-time

Covid-19 class taps experts to help students and the public avoid misinformation as the crisis evolves.

Raleigh McElvery | Department of Biology
May 21, 2021

Just a few months after the Covid-19 pandemic took hold, Alan Grossman was already mulling over an idea for a new class to help people make sense of the virus. As head of MIT’s Department of Biology, he was aware of the key role fundamental research would play in the coming months. From RNA viruses and genomic sequencing to antibodies and vaccines, MIT students and the general public would need reliable scientific information to understand the evolving situation — and discern fact from fiction.

Not long after, the thoughts he’d feverishly scribbled on paper scraps scattered around his house began to take shape. With the support of the MIT School of Science, Accessibility Office, MIT Video Productions, and others around the institute, the Department of Biology added a new fall subject to the course catalog: 7.00 (Covid-19, SARS-CoV-2 and the Pandemic). Undergraduates could take the class for credit, as notable researchers stepped up to the virtual podium to share their expertise in front of a public livestream.

Grossman brought his nascent plans to associate department head and Whitehead Institute for Biomedical Research Member Peter Reddien, and together the two brainstormed individuals who might be willing to lead the class and queue speakers. They reached out to professor of biology and Whitehead Institute Member Richard Young, who served as an advisor to the World Health Organization and National Institutes of Health when a different virus of unknown origins was spreading — HIV. Young was also quick to mount a collaborative research campaign against SARS-CoV-2, the virus that causes Covid-19.

“I give Alan a lot of credit,” Young says. “He thought that it was the responsibility of the department to take the lead in filling the Covid-19 knowledge niche, and asked me if I would take this on and find a partner.”

Young contacted Ragon Institute Associate Director Facundo Batista, a world-class expert in immunology and infectious disease. Batista recalls being hesitant at first to co-lead the class; he couldn’t fathom condensing the global emergency into a single course. “But then I realized that the onslaught of information was the very reason we needed to organize this class — to help students and the public avoid misinformation,” he says. “We were filling a gap that the whole world was experiencing.”

Together, Batista and Young generated a list of 14 experts in an array of pandemic-related areas, including Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, David Baltimore of Caltech, and Kizzmekia Corbett of the National Institutes of Health. Each geared their lecture toward MIT undergraduates with a minimal biology background, and defined key terms and concepts so non-biologists watching the livestream could follow along as well.

Although Batista and Young agree that remote learning pales in comparison to in-person classes, the livestream format opened the talks up to thousands more viewers, and allowed the speakers to present their work without the need for travel. The recordings of each Tuesday lecture were posted on the Department of Biology’s website shortly thereafter, permitting asynchronous viewing for people around the world. The livestream audience regularly exceeded 1,000, and the YouTube views for each recording ranged from 4,000-97,000 and climbing. In many cases, the week’s topic fortuitously coincided with current events. For instance, Corbett spoke about vaccine development just days after the results of Pfizer-BioNTech’s first clinical trial were announced. As one of the NIH scientists who collaborated with Moderna to design another important mRNA-based vaccine, Corbett was able to discuss her reaction to the news and her expectations for Moderna’s imminent clinical trial results.

In addition to the livestream audience, each week roughly 300 MIT undergraduates would enter the Zoom room and get the opportunity to ask questions during the Q&A. Participation was unusually high, Young and Batista recall, thanks to the recitation sessions led by graduate student and teaching assistant Lena Afeyan. Afeyan would walk the students through the fundamentals of molecular biology, virology, and any other topics slated to feature heavily in the upcoming lecture. She also invited trainees and medical residents from various institutions to attend, in order to introduce students to the next generation of scientists and health-care professionals. The supplementary reading materials from these sessions are still available online, so biology teachers and other members of the public can access them.

“When I heard that this class was being put together, I hoped I could help make the content more accessible for the students and anyone else joining us,” Afeyan says. “The responses we got were overwhelming. It was incredible to hear from so many teachers, researchers, and alums across the world who watched the course every week.”

Even today, Afeyan, Young, and Batista continue to receive international kudos from scientists and non-scientists alike. At one point, Young was even interviewed by a radio station in Tasmania about the course.

“I learned a lot from 7.00 — not only about Covid-19, but about immunology and biology in general,” says Lucas Marden, a first-year undergraduate who enrolled in the class. “I particularly enjoyed the focus on the real-world response to the pandemic. We learned about everything from designing and developing different tests, treatments, and vaccines, to the scale-up of these technologies. The scientific community’s response to Covid-19 has been incredibly impressive, and I loved learning about it from the people at the forefront of their fields.”

Now, Grossman says, the department is planning to offer the class again this coming fall. “The initial idea stemmed from the need to share clear and reliable information about the pandemic as it began spreading,” he explains. “Although we’ve been living with Covid-19 for over a year now, that need is still present today — perhaps more so as we continue to learn what it will take to tame the virus.”

The next iteration of 7.00 will begin in September, and likely feature some of the same speakers and topics, along with new experts in areas that have recently emerged, such as the evolving viral variants. By arming the MIT community and the public with information from leading experts, Grossman, Batista, Young, and Afeyan hope to help the world navigate this pandemic — and prevent the next one.

The proteins that package DNA to fit inside cells have another role: tuning gene expression
Raleigh McElvery
May 19, 2021

The DNA inside a single human cell is several meters long — yet it must be condensed to fit inside a space one-tenth the diameter of a hair. That’s like stretching a string from Philadelphia, Pennsylvania to Washington, D.C., and then trying to stuff it into a soccer ball. Imagine then organizing all of this information for each of the body’s 3 trillion cells! The DNA is condensed by proteins called histones that create a spool around which the DNA can wrap itself. How tightly the DNA is wound determines whether it is accessible enough for other proteins to bind to and copy into RNA, toggling gene expression levels up or down.

One specialized type of histone, H2A.Z, is ubiquitous and essential among multicellular organisms. But there have been conflicting reports about how it affects gene expression, especially during embryonic development.

Several years ago, Laurie Boyer’s lab at MIT was the first to show that H2A.Z wraps the DNA located around the start sites of most genes, where the molecular machine RNA polymerase II (RNAPII) binds to copy the DNA into RNA. Boyer’s team demonstrated that removing H2A.Z prevented embryonic cells from turning on genes that are important for forming organs and tissues. But scientists still weren’t sure how H2A.Z exerted its effects.

Now, in a recent Nature Structural and Molecular Biology study, a team from the Boyer lab, led by former postdoc Constantine Mylonas, has revealed how H2A.Z regulates the ability of RNAPII to properly transcribe DNA into the messages that specify all cell types in the body. The researchers found that in embryonic stem cells, H2A.Z serves as a “yellow traffic light,” signaling RNAPII to slow the process of transcribing DNA into RNA. Although there are other proteins that also contribute to RNAPII pausing, H2A.Z establishes a second barrier to transcription that allows gene expression to be tuned in response to developmental signals.

“H2A.Z appears to regulate how fast RNAPII begins to transcribe DNA, and this allows the cell time to respond to important cues that ultimately direct a stem cell to become a brain or heart cell, for example,” says Boyer, a professor of biology and biological engineering. “This connection was a critical missing piece of the puzzle, and explains why H2A.Z is essential for development across all multicellular organisms.”

Illustration of molecules
As RNAPII starts to transcribe a gene, it encounters a cluster of eight histones (a “nucleosome”) including H2A.z, which slows its progression — allowing for tuning of gene expression in response to developmental signals.

According to Boyer, H2A.Z’s role in gene expression has been difficult to pin down because previous approaches only provided static snapshots of how proteins interact with DNA days after loss of the histone. Boyer’s team overcame this shortcoming by leveraging a system that allowed for targeted degradation of H2A.Z within hours. They combined this technique with high-resolution genomic approaches and live cell imaging of RNAPII dynamics using super-resolution microscopy. With help from Ibrahim Cissé’s lab, they were able to visualize RNAPII dynamics in real time at the single molecule level in embryonic stem cells. Upon loss of H2A.Z, they found a remarkable increase in RNAPII movement in the cells, consistent with their genomic results showing a faster release of RNAPII and an increase in transcription in the absence of H2A.Z.

Next, the researchers plan to determine precisely how H2A.Z is targeted to the start sites of genes and how it forms a barrier to RNAPII passage.

Boyer says pinpointing the way histone variants like H2A.Z control gene expression is fundamental to understanding how developmental decisions are made, and will help researchers understand why misregulation of H2A.Z has been linked to diseases such as cancer.

“Emerging evidence indicates that DNA ‘packaging proteins’ like histones directly participate in how RNAPII can read and transcribe DNA,” she explains, “and that crucial connection wasn’t clear before.”

Image credits: courtesy of Laurie Boyer
Top image: Live cell super-resolution imaging showing RNAPII dynamics at a single molecule level in embryonic stem cells. The bright and colored clusters represent RNAPII molecules.

Citation:
“A dual role for H2A. Z. 1 in modulating the dynamics of RNA Polymerase II initiation and elongation.”
Nature Structural & Molecular Biology, online May 10, 2021, DOI: 10.1038/s41594-021-00589-3
Constantine Mylonas, Choongman Lee, Alexander L. Auld, Ibrahim I. Cisse, and Laurie A. Boyer.

Childhood hobbies jump-start a research career

MIT Biology junior Eduardo Canto tinkered with science long before he started studying Treacher Collins syndrome in the Calo lab.

Saima Sidik | Department of Biology
May 19, 2021

In seventh grade, Eduardo Canto wanted a dog. His mom said no, though. She didn’t want to spend her days vacuuming fur. They reached a compromise: Canto was allowed to have pet fish. Soon Canto’s disappointment with his new pets turned to curiosity. While he couldn’t train the fish to sit or roll over, he decided that breeding the fish could be a fun pastime.

An internet search told Canto that some aquarists use dried Indian almond leaves, a traditional Asian herbal remedy, to stimulate fish breeding, although no one is quite sure how the leaves do this. However, finding Indian almond leaves presented a problem for a kid without an Amazon account living far from the tree’s native habitat. On a whim, Canto picked up some similar-looking leaves in a park near his house in Puerto Rico. He knew they weren’t from an Indian almond tree, but he put them in the tank anyhow, just to see what would happen. A few days later, he noticed a collection of eggs attached to the bottom of a leaf!

Canto often took on little experiments like this, which caused his grandfather to predict early on that he would have a scientific career. Eight years after the breeding endeavor, Canto is fulfilling his grandfather’s prediction by studying Course 7 (Biology) at MIT, where he’s currently in his third year of a bachelor’s degree. Once again, fish have come into Canto’s life — he’s working in Eliezer Calo’s lab, where researchers use zebrafish to study a genetic disorder called Treacher Collins syndrome, which causes deformities in eyes, ears, cheekbones, and chins.

Throughout middle school and high school, Canto dipped his toes into many scientific disciplines. School science fairs motivated him to build a dry ice-powered trolley, a solar-powered water heater, and start a vegetable garden.

Sometimes, he admits, his motivation for joining science clubs wasn’t lofty. “I joined the math club because I got to miss a day of school every year for their annual competition,” he says with a laugh. But he also talks excitedly about his early experiments, particularly in biology. “I’ve always loved working with my hands,” he says.

Canto’s father, a medical doctor, encouraged his son’s interest by letting Canto shadow him at work. He also started a molecular biology summer program at Canto’s high school that taught students how to pipette and do simple experiments. By the time Canto applied to college, he was convinced he wanted to study biology, and MIT drew his attention because of its reputation as a top science school with excellent biology teachers. He knew it was the right choice for him when he attended Campus Preview Weekend, and found a large Puerto Rican community ready to welcome him. Even far from the island, he felt at home.

Canto has kept up with his roots since joining MIT by playing on a soccer team for Puerto Rican students. He’s also become part of a new community in a lab run by Eliezer Calo — who is a Puerto Rican himself. The lab is interested in ribosomes, the molecular machines that build proteins. Treacher Collins syndrome arises when cells can’t make ribosomes properly, and Canto wants to understand why that is.

Before Canto joined the Calo lab, the group had already started studying a protein called DDX21 that’s involved in making ribosomes in both humans and zebrafish. When genetic mutations in zebrafish cause DDX21 to go to the wrong part of the cell, the fish develop jaw deformations that mirror Treacher Collins syndrome. The Calo lab thinks cells with mislocalized DDX21 probably don’t produce ribosomes as well as normal cells, but they’re still testing this hypothesis.

Canto wants to probe the relationship between DDX21 and Treacher Collins syndrome further, but fish reproduce slowly, so they’re not ideal organisms for his research. Instead, he’s built a strain of Escherichia coli bacteria that carry DDX21 in place of the equivalent bacterial gene. DDX21 helps these bacteria survive the stress associated with cold temperatures, so without it, the bacteria will die in the cold. Canto hopes to take advantage of this trait by finding small molecules that stop the bacteria from growing at low temperatures — just like a DDX21 mutation would. Studying how these molecules bind DDX21 will help him understand which parts of this protein are important for its function.

The possibility that this work will one day reveal how Treacher Collins syndrome develops in patients is rewarding to Canto, and in fact he hopes helping patients will soon become his life’s focus. He wants to attend medical school, and eventually become a doctor. The human physiology class he took last semester was one of his favorites, even though it was over Zoom due to the COVID-19 pandemic. Becoming a doctor will let him help others while studying topics he finds fascinating. “Medicine is like biology on steroids!” he says.

And who knows — one day after he’s a doctor, maybe he’ll even get that pet he’s always wanted. But unlike Canto’s interest in biology, some of his interests have evolved over time. These days, he prefers cats over dogs.

Photo credit: Saima Sidik
Posted: 5.19.21
Kristin Knouse

Education

  • PhD, 2017, MIT; MD, 2018, Harvard Medical School
  • Undergraduate: BS, 2010, Biology, Duke University

Research Summary

We aim to understand how tissues sense and respond to damage with the goal of developing novel treatments for diverse human diseases. We focus on the mammalian liver, which has the unique ability to completely regenerate itself, in order to identify the molecular requirements for effective organ repair. To this end, we innovate genetic, molecular, and cellular tools that allow us to investigate and modulate organ injury and regeneration directly within living organisms.

Awards

  • NIH Director’s Early Independence Award, 2018
  • Henry Asbury Christian Award, 2018
Olivia Corradin

Education

  • PhD, 2015, Case Western Reserve University
  • BS, 2010, Biochemistry, Marquette University

Research Summary

Our lab studies genetic and epigenetic variation that contributes to human disease by disrupting gene expression programs. We utilize biological insights into the mechanisms of gene regulation in order to determine the impact of disease-associated variants on cellular function. We aim to identify actionable insights into disease pathogenesis by studying the confluence of genetic and epigenetic risk factors of human diseases, including multiple sclerosis and opioid use disorder.

Awards

  • NIH Director’s Pioneer Award Program Avenir Award, 2017
Whitehead Institute appoints two new faculty members
Merrill Meadow | Whitehead Institute
May 4, 2021

Whitehead Institute director Ruth Lehmann announced the appointment of two dynamic new Members: Olivia Corradin, currently a Whitehead Fellow, and Sinisa Hrvatin, currently an instructor and postdoctoral fellow at Harvard Medical School. Both will also become assistant professors of biology at Massachusetts Institute of Technology (MIT). Corradin’s joint appointments begin in July 2021, Hrvatin’s in January 2022.

“Both Olivia and Sinisa are creative, collaborative, and highly accomplished early-career scientists,” says Lehmann. “Each has impressed the Whitehead Institute and MIT faculties with their drive, intellect, and their scientific vision. We look forward to their contributions — as researchers, educators, and colleagues — for many years to come.”

Corradin investigates gene variants, small differences in DNA sequence, which can prompt disease-causing changes in gene regulation. During her nearly five years as a Whitehead Fellow, her lab defined the concept of “outside variants,” which helps to explain how genetic variants increase one’s likelihood of developing disease. She also developed a method to identify the cell type affected by a specific disease-linked variant; and then used it to single out oligodendrocytes as one type of brain cell involved in multiple sclerosis. Most recently, Corradin created an approach for defining epigenetic variation — which is caused by factors other than DNA sequence changes — in some individuals with opioid use disorder; this will help researchers’ identify genes associated with the disorder.

Before becoming the Scott Cook and Signe Ostby Fellow at Whitehead Institute in 2016, Corradin earned a PhD at Case Western Reserve University. There her research focused on genetic and epigenetic dysregulation in human disease, and she pioneered approaches to predict gene targets of regulatory DNA sequences associated with variants.

“I’m incredibly excited to be stepping into this new stage at Whitehead Institute and MIT Biology,” Corradin says. “I look forward to continued collaboration and to becoming a part of the rich history that shapes our Institute.”

Hrvatin investigates how organisms enter torpor and hibernation and how their cells adapt and survive in these states. As a postdoctoral research fellow in the lab of Harvard Medical School neurobiologist Michael Greenberg, Hrvatin established an experimental paradigm for studying a hibernation-like behavior in mice — and used this system to discover the neurons that control entry into this state. In addition, he pioneered the Paralleled Enhancer Single Cell Assay platform — a new method to generate cell-type-specific AAV vectors that can be used for targeted human gene therapy, as well as to control defined neuronal cell types across species, including in hibernating animals.

Hrvatin earned a PhD in stem cell and regenerative medicine from Harvard University, where he studied the process of directed differentiation from human embryonic stem cells to pancreatic beta cells. After his graduate work, he served as a postdoctoral associate at MIT in the lab of Daniel Anderson, where he investigated approaches for targeted siRNA delivery to pancreatic beta cells. Hrvatin also founded ReadCube, a startup dedicated to disseminating access to scientific literature and developing reference management tools for research scientists.

“I’ve always been inspired by the exceptional scientists, educators, pioneers, and visionaries at the Whitehead Institute and MIT Biology,” Hrvatin says. “I am absolutely thrilled for the opportunity to learn from and become a part of this extraordinary community.”

Biologists discover a trigger for cell extrusion

Study suggests this process for eliminating unneeded cells may also protect against cancer.

Anne Trafton | MIT News Office
May 5, 2021

For all animals, eliminating some cells is a necessary part of embryonic development. Living cells are also naturally sloughed off in mature tissues; for example, the lining of the intestine turns over every few days.

One way that organisms get rid of unneeded cells is through a process called extrusion, which allows cells to be squeezed out of a layer of tissue without disrupting the layer of cells left behind. MIT biologists have now discovered that this process is triggered when cells are unable to replicate their DNA during cell division.

The researchers discovered this mechanism in the worm C. elegans, and they showed that the same process can be driven by mammalian cells; they believe extrusion may serve as a way for the body to eliminate cancerous or precancerous cells.

“Cell extrusion is a mechanism of cell elimination used by organisms as diverse as sponges, insects, and humans,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, a Howard Hughes Medical Institute investigator, and the senior author of the study. “The discovery that extrusion is driven by a failure in DNA replication was unexpected and offers a new way to think about and possibly intervene in certain diseases, particularly cancer.”

MIT postdoc Vivek Dwivedi is the lead author of the paper, which appears today in Nature. Other authors of the paper are King’s College London research fellow Carlos Pardo-Pastor, MIT research specialist Rita Droste, MIT postdoc Ji Na Kong, MIT graduate student Nolan Tucker, Novartis scientist and former MIT postdoc Daniel Denning, and King’s College London professor of biology Jody Rosenblatt.

Stuck in the cell cycle

In the 1980s, Horvitz was one of the first scientists to analyze a type of programmed cell suicide called apoptosis, which organisms use to eliminate cells that are no longer needed. He made his discoveries using C. elegans, a tiny nematode that contains exactly 959 cells. The developmental lineage of each cell is known, and embryonic development follows the same pattern every time. Throughout this developmental process, 1,090 cells are generated, and 131 cells undergo programmed cell suicide by apoptosis.

Horvitz’s lab later showed that if the worms were genetically mutated so that they could not eliminate cells by apoptosis, a few of those 131 cells would instead be eliminated by cell extrusion, which appears to be able to serve as a backup mechanism to apoptosis. How this extrusion process gets triggered, however, remained a mystery.

To unravel this mystery, Dwivedi performed a large-scale screen of more than 11,000 C. elegans genes. One by one, he and his colleagues knocked down the expression of each gene in worms that could not perform apoptosis. This screen allowed them to identify genes that are critical for turning on cell extrusion during development.

To the researchers’ surprise, many of the genes that turned up as necessary for extrusion were involved in the cell division cycle. These genes were primarily active during first steps of the cell cycle, which involve initiating the cell division cycle and copying the cell’s DNA.

Further experiments revealed that cells that are eventually extruded do initially enter the cell cycle and begin to replicate their DNA. However, they appear to get stuck in this phase, leading them to be extruded.

Most of the cells that end up getting extruded are unusually small, and are produced from an unequal cell division that results in one large daughter cell and one much smaller one. The researchers showed that if they interfered with the genes that control this process, so that the two daughter cells were closer to the same size, the cells that normally would have been extruded were able to successfully complete the cell cycle and were not extruded.

The researchers also showed that the failure of the very small cells to complete the cell cycle stems from a shortage of the proteins and DNA building blocks needed to copy DNA. Among other key proteins, the cells likely don’t have enough of an enzyme called LRR-1, which is critical for DNA replication. When DNA replication stalls, proteins that are responsible for detecting replication stress quickly halt cell division by inactivating a protein called CDK1. CDK1 also controls cell adhesion, so the researchers hypothesize that when CDK1 is turned off, cells lose their stickiness and detach, leading to extrusion.

Cancer protection

Horvitz’s lab then teamed up with researchers at King’s College London, led by Rosenblatt, to investigate whether the same mechanism might be used by mammalian cells. In mammals, cell extrusion plays an important role in replacing the lining of the intestines, lungs, and other organs.

The researchers used a chemical called hydroxyurea to induce DNA replication stress in canine kidney cells grown in cell culture. The treatment quadrupled the rate of extrusion, and the researchers found that the extruded cells made it into the phase of the cell cycle where DNA is replicated before being extruded. They also showed that in mammalian cells, the well-known cancer suppressor p53 is involved in initiating extrusion of cells experiencing replication stress.

That suggests that in addition to its other cancer-protective roles, p53 may help to eliminate cancerous or precancerous cells by forcing them to extrude, Dwivedi says.

“Replication stress is one of the characteristic features of cells that are precancerous or cancerous. And what this finding suggests is that the extrusion of cells that are experiencing replication stress is potentially a tumor suppressor mechanism,” he says.

The fact that cell extrusion is seen in so many animals, from sponges to mammals, led the researchers to hypothesize that it may have evolved as a very early form of cell elimination that was later supplanted by programmed cell suicide involving apoptosis.

“This cell elimination mechanism depends only on the cell cycle,” Dwivedi says. “It doesn’t require any specialized machinery like that needed for apoptosis to eliminate these cells, so what we’ve proposed is that this could be a primordial form of cell elimination. This means it may have been one of the first ways of cell elimination to come into existence, because it depends on the same process that an organism uses to generate many more cells.”

Dwivedi, who earned his PhD at MIT, was a Khorana scholar before entering MIT for graduate school. This research was supported by the Howard Hughes Medical Institute and the National Institutes of Health.

3 Questions: Sheena Vasquez and Mandana Sassanfar on building an outreach initiative from scratch

Graduate student and outreach director discuss efforts by the Department of Biology’s faculty, students, and staff to engage local community college students in scientific research.

Raleigh McElvery | Department of Biology
May 4, 2021

On June 10 of last year, MIT’s Department of Biology took the day to engage in open conversations about racial bias, diversity, and inclusion in support of the #ShutDownSTEM national initiative. These discussions spurred students, faculty, and staff to come together and form their own initiative. Known as the Community College Partnership, this program hopes to develop strong ties with local community colleges that are within commuting distance and serve diverse, nontraditional students — in order to increase access to MIT’s on-site and online resources. 

The department’s existing outreach programs — including the MIT Summer Research Program in Biology (MSRP-Bio), Quantitative Methods Workshop (QMW), and LEAH Knox Scholars Program — engage local high school students and non-MIT undergraduates from historically underrepresented groups in science. However, as of last year, the department had no research training opportunities geared toward community college students. The Community College Partnership is filling this gap by organizing virtual career panels, workshops, and seminars for students from Bunker Hill Community College and Roxbury Community College. In doing so, the initiative aims to encourage community college students from the Boston area to participate in additional MIT research opportunities, such as MSRP-Bio and QMW. Graduate student Sheena Vasquez, who spearheaded this initiative, and Mandana Sassanfar, the department’s director of outreach, sat down to discuss building a new program from scratch and how to plan for long-term success.

Q: What was your impetus for creating a program geared toward community college outreach?

Vasquez: I consider community college outreach very important for personal reasons. Back when I was applying to college, I couldn’t afford to attend a traditional four-year institution. I was also unsure what I wanted to major in, and I needed to stay close to home to take care of my family. I attended Georgia Perimeter College — a two-year community college — before transferring to the University of Georgia to finish my bachelor’s degree. I was able to participate in programs funded by the National Science Foundation, which led me to MIT for several summers as part of MSRP-Bio.

Looking back, I don’t think I would be a biology graduate student today if I hadn’t attended a community college. It also allowed me to see firsthand the talent, drive, and diversity at community colleges. And yet, at times these students are overlooked and underestimated by the general public. After our #ShutDownSTEM event last summer, it seemed like an ideal time to start engaging local community colleges in MIT’s biology research.

Sassanfar: I agree. It was by admitting bright students like Sheena to programs like MSRP that I realized the lack of initiatives aimed at community colleges. #ShutDownSTEM generated the energy and interest we needed to finally catalyze something like this. It was the missing link.

Q: What are the goals of the program, and how will you measure success?

Sassanfar: Our goals are twofold. First, we want to ensure that these students go far and reach their career goals — and possibly discover new goals that they didn’t realize were possible. Second, we hope to educate our own MIT community about the community college population, and build long-lasting relationships. This way, everyone will benefit.

Vasquez: We’ll be able to gauge the strength of these budding relationships by tracking how many students go on to participate in MSRP-Bio, QMW, and other rigorous research opportunities after attending our events. We also hope to create a team of graduate student mentors who can offer their expertise in grant writing and applying to graduate or other post-secondary schools.

Q: What challenges have you had to overcome in order to launch an outreach program aimed at a new community? How have you surmounted these difficulties?

Vasquez: The first challenge we faced was figuring out which community colleges to reach out to, and establishing points of contact there. We connected with Bunker Hill Community College first because of the diversity of students that attend. In addition, they had an active diversity, equity, and inclusion office, but no formal relationship with MIT Biology yet.

The next challenge was figuring out how to teach lab techniques virtually during our four-day workshop. We experimented with several different platforms before settling on Zoom. We also ended up sharing video recordings of ourselves in lab, and included tutorials on open-source software such as SnapGene and PyMOL — which allowed students to try their hand at procedures like DNA cloning, PCR, and interpreting protein structures. We asked everyone to fill out a survey at the very end, and 82 percent said they enjoyed the workshop and gained new skills. Ninety-six percent said they’d be interested in learning more about applying to graduate school, and some students have even reached out to us individually to continue the discussion.

Sassanfar: As Sheena alluded to, we’ve learned over the years that the secret to success is finding at least one faculty member or administrator at the other institution who is equally passionate about forming a partnership. In the case of Roxbury Community College, it took one meeting with a handful of faculty members to identify a professor who was willing to help make things happen. We do our part and they do their part; there has to be seamless communication.

My last piece of advice is that it’s vital for an outreach initiative to be focused. Go for depth, not breadth. It would be impossible to engage all community colleges in the greater Boston area. Instead, we are working hard to form strong relationships with a few in particular. That’s essential to creating something that’s long-lasting.

Up for a challenge in the lab and on the mat

While exploring a variety of research opportunities, senior Jose Aceves-Salvador has also thrown himself into mentoring, teaching, and cheerleading.

Hannah Meiseles | MIT News Office
April 28, 2021

At 5:30 a.m., his alarm would start blaring. Reluctant to get up, Jose Aceves-Salvador would hear his parents outside his door, bustling to get ready for work. “Ponte las pilas!” they would shout, using a Spanish idiom expressing encouragement to work hard.

The expression would stick with Aceves-Salvador throughout high school as he dreamed of going to college. Although neither of his parents had college degrees, they were both huge supporters of his decision. As Mexican immigrants who had moved to Los Angeles in their youth, their goal was to see their son achieve a better future.

“They didn’t know much about applying to college, but they knew that when you go, you’re set up for life,” explains Aceves-Salvador. “Whenever I’d hit a low, I’d think of how they’d tell me to work hard and keep going.”

To get a first taste of campus life, Aceves-Salvador attended a program at MIT called Minority Introduction to Engineering and Science (MITES) during the summer before his junior year of high school. MITES allowed Aceves-Salvador to take a genomics class at the Broad Institute of MIT and Harvard. The experience exposed him to the exciting and ever-changing world of scientific research.

“After MITES was over, I knew I wanted to go back to MIT. There was so much I still wanted to learn and explore,” Aceves-Salvador says. “In my mind, MIT was a huge reach school. But I couldn’t let go of the goal and figured I’d apply anyway.”

Aceves-Salvador was admitted and is now a senior studying biology with a concentration in education. “I love the learning process, and in biology there’s a never-ending cycle of questions to explore,” he says enthusiastically. “There are also so many opportunities to learn from failures and successes along the way.”

Aceves-Salvador wanted to do research the moment he arrived on campus, but struggled to get a lab position without any prior experience. Fortunately, in his sophomore year an interview with Xun Gong, a postdoc with the Strano Research Group, led to an opportunity. The lab had recently observed a new phenomenon in single-walled carbon nanotubes and wanted to investigate further. Aceves-Salvador joined the group and led the side project with Gong’s mentorship. “The project, and the fact that we were going into the unknown and exploring a new phenomenon perfectly fit my mentality, so I immediately said yes,” says Aceves-Salvador. “I eventually got my first taste of real science and have been hooked ever since.”

Since his first project, Aceves-Salvador has continued to do research, in multiple MIT labs and at the University of California at Los Angeles one summer. He has enjoyed working on everything from modeling protein behavior to developing a gut microphysical system. “As a college student, you come in barely knowing what’s out there to explore. I’ve tried to use my undergraduate degree to learn more about biology as a field before committing to something,” he says.

Across his different lab experiences, Aceves-Salvador has noted the lack of Latinx representation in science. He is devoted to encouraging greater minority representation in STEM and has served as a teaching assistant and mentor for MITES and the MIT Leadership Training Institute. These roles have allowed him to share his empowering story and love for education by teaching others. “I really wouldn’t be here if it weren’t for programs like MITES. I’m so grateful I can give back and be part of its legacy,” Aceves-Salvador says.

For an afterschool program he led in Los Angeles, Aceves-Salvador shaped the science curriculum he teaches to be more exciting to young learners. Students were challenged through hands-on activities, like creating chemical reactions, to make their own observations. “At a young age you’re so curious and curiosity is what science is all about,” says Aceves-Salvador. “But oftentimes, this curiosity gets stifled through outside pressures. In the hands-on activities I help lead, I try to create an open environment that encourages students to feel comfortable asking questions.”

Aceves-Salvador noticed the same approaches being used abroad during his international teaching experiences. Through MISTI Global Teaching Labs, he has traveled to Spain and Mexico to teach biology, math, health sciences, and chemistry. In Spain, Aceves-Salvador got to lead a discussion with local teachers on how to approach and encourage STEM education. “At least in the school I was placed in, I saw greater opportunities for students to explore different corners of science in their projects,” he notes. “The community-centric classrooms were also more focused on discussion among the students and less lecture.”

Outside of teaching and research, Aceves-Salvador enjoys channeling his passionate energy into dance and cheer. He has been part of MIT Cheerleading and DanceTroupe. These activities have pushed him physically, for example training him to lift cheerleaders on his shoulders and throw them into the air. He credits the intense nature of workout routines for creating a deep communal bond between members. “You share a connection with people after they’ve seen you fall on your face,” he jokes. “You can’t really hide anything at that point.”

This fall, Aceves-Salvador will be attending Harvard Medical School to pursue a PhD through the Biological and Biomedical Sciences program. He looks forward to continuing to explore different realms in science, as well as encouraging other young minority students to do the same. “Growing up, I never expected myself to be here in this position today. Even when I actually got into MIT, I faced a lot of pushback. People questioned my abilities and attributed my successes to luck,” Aceves-Salvador explains.

“It took me four years to leave that mentality. Now, I want to be a driving force to change that stigma. I want people to know that the reason we’re here is because we deserve to be here. And we’re going to do big things just like anyone else.”

Using CRISPR as a research tool to develop cancer treatments

KSQ Therapeutics uses technology created at MIT to study the role of every human gene in disease biology.

Zach Winn | MIT News Office
April 23, 2021

CRISPR’s potential to prevent or treat disease is widely recognized. But the gene-editing technology can also be used as a research tool to probe and understand diseases.

That’s the basic insight behind KSQ Therapeutics. The company uses CRISPR to alter genes across millions of cells. By observing the effect of turning on and off individual genes, KSQ can decipher their role in diseases like cancer. The company uses those insights to develop new treatments.

The approach allows KSQ to evaluate the function of every gene in the human genome. It was developed at MIT by co-founder Tim Wang PhD ’17 in the labs of professors Eric Lander and David Sabatini.

“Now we can look at every single gene, which you really couldn’t do before in a human cell system, and therefore there are new aspects of biology and disease to discover, and some of these have clinical value,” says Sabatini, who is also a co-founder.

KSQ’s product pipeline includes small-molecule drugs as well as cell therapies that target genetic vulnerabilities identified from their experiments with cancer and tumor cells. KSQ believes its CRISPR-based methodology gives it a more complete understanding of disease biology than other pharmaceutical companies and thus a better chance of developing effective treatments to cancer and other complex diseases.

A tool for discovery

KSQ’s scientific co-founders had been studying the function of genes for years before advances in CRISPR allowed them to precisely edit genomes about 10 years ago. They immediately recognized CRISPR’s potential to help them understand the role of genes in disease biology.

During his PhD work, Wang and his collaborators developed a way to use CRISPR at scale, knocking out individual genes across millions of cells. By observing the impact of those changes over time, the researchers could tease out the functionality of each gene. If a cell died, they knew the gene they knocked out was essential. In cancer cells, the researchers could add drugs and see if knocking out any of the genes affected drug resistance. More sophisticated screening methods taught the researchers how different genes inhibit or drive tumor growth.

“It’s a tool for discovering human biology at scale that was not possible before CRISPR,” says KSQ co-founder Jonathan Weissman, a professor of biology at MIT and a member of the Whitehead Institute. “You can search for genes or mechanisms that can modulate essentially any disease process.”

Wang credits Sabatini with spearheading the commercialization efforts, speaking with investors, and working with MIT’s Technology Licensing Office. Wang also says MIT’s ecosystem helped him think about bringing the technology out of the lab.

“Being at MIT and in the Cambridge area probably made the leap to commercialization a bit easier than it would have been elsewhere,” Wang says. “A lot of the students are entrepreneurial, there’s that rich tradition, so that helped shape my mindset around commercialization.”

Weissman had developed a complementary, CRISPR-based technology that Wang and Sabatini knew would be useful for KSQ’s discovery platform. Around 2015, as the founders were starting the company, they also brought on co-founder William Hahn, a member of the Broad Institute of MIT and Harvard, a professor at Harvard Medical School, and the chief operating officer of the Dana-Farber Cancer Institute.

Since then, the company has advanced Wang’s method.

“They’re able to scale this to a degree that is not possible in any academic lab, even David’s,” Wang says. “The cell lines I used for my experiments were just what was easy to grow and what was in the lab, whereas KSQ is thinking about what therapies aren’t available in certain cancers and deciding what diseases to go after.”

KSQ’s gene evaluations include tens of millions of cells. The company says the data it collects has been predictive of past successes and failures in cancer drug development. Weissman equates the data to “a roadmap for finding cancer vulnerabilities.”

“Cancers have all these different escape routes,” Weissman says. “This is a way of mapping out those escape routes. If there are too many, it’s not a good target to go after, but if there is a small number, you can now start to develop therapies to block off the escape routes.”

From discovery to impact

KSQ’s lead drug candidate is in preclinical development. It targets a DNA-repair pathway identified using an updated version of Wang’s technique. The drug could treat multiple ovarian cancers as well as a disease called triple-negative breast cancer. KSQ is also currently developing a cell therapy to boost the immune system’s ability to fight tumors.

“I’ve always thought the best biotech companies start with information that other people don’t have,” Sabatini says. “I think biotech companies have to have some discovery to them. That’s enabled KSQ to go in different directions.”

The founders feel KSQ has already validated their approach and stimulated further interest in using CRISPR as a research tool.

“There’s a lot of interest in CRISPR as a therapeutic, and that’s an important aspect,” Weissman says. “But I’d argue equally important both in discovery and in therapeutics will be [using CRISPR] to identify the targets you want to go after to affect disease process. Your ability to engineer genomes or make drugs depends on knowing what genes you want to change.”