Author: mantulin

2021 MITx Prize winners build community on campus and across the globe

MIT instructors honored for creating multidimensional, multidisciplinary online courses that help learners everywhere address real-world problems.

MIT Open Learning
June 7, 2021

On May 14, six MIT instructors were honored with the 2021 MITx Prize for Teaching and Learning in MOOCs. The prize, established in 2016, honors excellence in creating Massive Open Online Courses (MOOCs) for MITx on edX. Anyone in the MIT community can submit nominations, including MITx MOOC creators, and awardees are selected by the MITx Faculty Advisory Committee.

The award was given to two courses this year, honoring faculty and instructors from four disciplines. Jonathan Gruber, Ford Professor of Economics, was honored for his 14.01x (AP Microeconomics) course, which uses MIT materials geared toward high school learners to help them prepare for the College Board exam. The other course recognized, 15.480x (The Science and Business of Biotechnology), was created by professors Andrew Lo of the MIT Sloan School of Management and Harvey Lodish of the Department of Biology, along with graduate students Zied Ben Chaouch of the Department of Electrical Engineering and Computer Science (EECS) and Kate Koch of the Department of Biology, as well as Shomesh Chaudhuri ’14, PhD ’18, an EECS graduate.

The MITx Faculty Advisory Committee assesses prize nominees on four criteria: effective and engaging teaching methods, learner-focused innovation, residential impact and reuse, and global reach and impact. It is that last criterion that has drawn the most focus over the past year; in the wake of the Covid-19 crisis, demand for the established, high-quality resources offered by MIT Open Learning has been higher than ever.

“Now more than ever, by opening MIT teaching and learning to the world, our MITx courses are making a global impact,” says Dean for Digital Learning Krishna Rajagopal. “The courses honored with this award are exemplars of the best of MITx, and of MIT. They reach quite different audiences; high school students in one case, current and future leaders in biotechnology in the other. In both cases, they are doing so in ways that are sparking new curiosity and interest and opening new opportunities for their learners worldwide.”

Gruber’s Microeconomics course is a perfect example of a learning resource that has grown beyond its original purpose to reach a diverse international audience. Gruber first designed the course in 2017 to fill the void of preparatory materials available to U.S. students planning to take the AP Microeconomics exam; he notes that few high schools offer any kind of support or formal training for the test. The MOOC is structured around the exam curriculum, to serve either as standalone training or as a supplement to instructor-led courses. But perhaps in part because of its wide-ranging, pop-culture savvy appeal (Gruber uses LeBron James’ basketball career, Kim Kardashian’s Instagram account, and the pros and cons of attending university as just a few of his real-world economics examples) the course has found a truly global audience with learners from 180 countries.

Gruber has also used the course to develop and implement a very practical economic policy of his own. He has done away with assigning a required — and costly — textbook for his students in his residential MIT version of the course, instead assigning materials from the MOOC and other free, open source MIT learning materials as a supplement to class lectures and notes. David Autor, Ford Professor of Economics, in support of the course’s nomination, commended the “labor of love” that is Gruber’s course, and how with each new iteration of the MOOC, his colleague builds bridges for high school students, “[opening] pathways that were previously cloudy or just invisible.” Over time, says Autor, the course will “foster diversity and inclusion by seeding opportunity where it was absent.”

The Science and Business of Biotechnology course team was no less ambitious in creating their multidisciplinary exploration of the industry, setting up the course based on the comprehensive, research-led approach they’d like to see companies adopt. Like Gruber, course leaders Andrew Lo and Harvey Lodish have personal connections to their subject: Lo was moved to make change in the sector after experiencing disillusionment with biotech during loved ones’ battles with cancer. Lodish has witnessed the enormous impact of the biotech industry on both personal and professional levels: years after he co-founded Genzyme, his daughter gave birth to a son who depends on one of the company’s medicines for treatment of a chronic health condition.

The team’s dedication and well-balanced approach to a multifaceted industry has been a smashing success. Calling Lo and Lodish “superstars” in his letter of support, Institute Professor Robert Langer lauded the course’s comprehensive approach to the subject matter, finding it essential for those who would seek to make a real impact on the biotech industry. Heidi Pickett, assistant dean for the MIT Sloan Master of Finance Program, also praised the combination of subject areas explored throughout the course, citing its ability to redress weaknesses in individual learners’ skill sets; those coming from a finance background, for example, would benefit from a deeper engagement with the science of biotech, while still gaining knowledge in their primary field. She also spoke to the course’s wide appeal: “Considering the importance of topics discussed presented in 15.480x, it is no wonder the course attracted learners from around the world bringing different backgrounds and perspectives,” she says, adding that lively exchanges between users on the course’s discussion boards greatly enhanced the learning experience.

After a year when so many learners struggled to adapt to a sudden shift to remote education, MITx Director Dana Doyle finds ample reason to celebrate the power of intentional online teaching and learning. “In a time when people everywhere have felt both increasingly isolated and increasingly connected by the experience of the pandemic, it’s so heartening to witness how these courses have brought learners together to dive into important, complex global issues.”

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.

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.”

Five from MIT elected to American Academy of Arts and Sciences for 2021

Prestigious honor society announces more than 250 new members.

MIT News Office
April 23, 2021

Five MIT faculty members are among more than 250 leaders from academia, business, public affairs, the humanities, and the arts elected to the American Academy of Arts and Sciences, the academy announced Thursday.

One of the nation’s most prestigious honorary societies, the academy is also a leading center for independent policy research. Members contribute to academy publications, as well as studies of science and technology policy, energy and global security, social policy and American institutions, the humanities and culture, and education.

Those elected from MIT this year are:

  • Linda Griffith, the School of Engineering Professor of Teaching Innovation, Biological Engineering, and Mechanical engineering;
  • Muriel Médard, the Cecil H. Green Professor in the Department of Electrical Engineering;
  • Leona Samson, professor of biological engineering and biology;
  • Scott Sheffield, the Leighton Family Professor in the Department of Mathematics; and
  • Li-Huei Tsai, the Picower Professor in the Department of Brain and Cognitive Sciences.

“We are honoring the excellence of these individuals, celebrating what they have achieved so far, and imagining what they will continue to accomplish,” says David Oxtoby, president of the academy. “The past year has been replete with evidence of how things can get worse; this is an opportunity to illuminate the importance of art, ideas, knowledge, and leadership that can make a better world.”

Since its founding in 1780, the academy has elected leading thinkers from each generation, including George Washington and Benjamin Franklin in the 18th century, Maria Mitchell and Daniel Webster in the 19th century, and Toni Morrison and Albert Einstein in the 20th century. The current membership includes more than 250 Nobel and Pulitzer Prize winners.

School of Science announces 2021 Infinite Mile awards

Thirteen staff members recognized for dedication to School of Science and to MIT.

School of Science
April 9, 2021

The MIT School of Science has recognized 13 staff members with the 2021 Infinite Mile Award.

Staff are nominated for Infinite Mile Awards, presented annually since their creation in 2001, by their peers for going above and beyond in their roles and making MIT a better place. Their support for the School of Science, and the Institute community as a whole, has been invaluable, especially as we pass the one-year mark of work-from-home and social distancing due to the Covid-19 pandemic.

The following are the 2021 School of Science Infinite Mile winners.

  • Rebecca Chamberlain, administrative officer in the Department of Biology, was nominated by Professor Stephen Bell because Chamberlain “makes things easier for everyone in the department and this has never been more true than in this trying year. Even as she has taken on so much more, she has continued to maintain a friendly, patient, and unflappable attitude that makes her all the more remarkable.”
  • Janice Chang, academic administrator in the Department of Biology, was nominated by MIT Human Resources administrator Helene Kelsey because Chang is “truly exceptional, strives for perfection, and her skills and work ethic are recognized throughout the department. Janice has embraced the associated challenges with wisdom, a common-sense approach, dedication, goodwill, and a willingness to devote endless additional hours to the tasks at hand.”
  • Emma Dunn, undergraduate programs assistant in the Department of Physics, was nominated by Academic Administrator Catherine Modica because, when campus closed, “it was Emma who came up with all the ideas we used to try to reach out to our students, […] tracking their arrivals at home to make sure they were safe, and creating and sending shipments of care packages to every undergraduate major to remind them that we were […] thinking about them and standing ready to help.”
  • Jennifer Fentress, communications officer in the Department of Earth, Atmospheric and Planetary Sciences, was nominated by professor of physics and department head Robert van der Hilst; associate professor of physics David McGee; and staff colleagues Julia Keller, Megan Jordan, Angela Ellis, Maggie Cedarstrom, Brandon Milardo, and Scott Wade because Fentress “has helped advance the work of the school and MIT more broadly. At every opportunity, she ensures that the voices of EAPS research scientists are well-represented.”
  • Laura Frawley, a lecturer in the Department of Brain and Cognitive Sciences, was nominated by Professor Michale Fee and staff colleagues Kate White and Kimberli DeMayo because Frawley “has dedicated so much time and effort into learning all the new tools and resources available to help faculty convert to remote learning. […] All in all, Laura has been a savior this year!”
  • Brittany Greenough, an events planning assistant in the Picower Institute for Learning and Memory, was nominated by Picower Institute director and professor of brain and cognitive sciences Li-Huei Tsai and Administrative Officer William Lawson because, “[i]n this new, virtual environment, Brittany has taken it upon herself to be the resident expert with transitioning events to online formats.”
  • Chhayfou Hong, a financial assistant in the Laboratory for Nuclear Science, was nominated by professors of physics Jesse Thaler, Mike Williams, Joseph Formaggio, and Philip Harris because “without Chai’s herculean efforts here, the IAIFI [NSF AI Institute for Artificial Intelligence and Fundamental Interactions] would not exist, and MIT would have missed out on housing one of the inaugural NSF AI institutes — and on $20 million in revenue over the next five years.”
  • Beverly La Marr, a test engineer in the MIT Kavli Institute for Astrophysics and Space Research, was nominated by Kavli Institute director and professor of physics Robert Simcoe and principal research scientists Marshall Bautz, Ronald Remillard, and Gregory Prigozhin because La Marr “has played an essential part in MKI’s success in space with flagships, mid-sized, and small missions; and in fact, at this moment, three missions bearing her intellectual ‘fingerprints’ are all producing exciting scientific data from space. Her contributions to her colleagues are no less significant.”
  • Brian Pretti, a facilities and operations administrator in the Department of Chemistry, was nominated by professor and department head Troy Van Voorhis and administrative officer Richard Wilk because Pretti “is someone who goes far above and beyond his usual call of duty. He is also a joy to work with, no matter the stress or difficulty of the situation. Brian exemplifies all of the qualities of someone who truly cares about the quality of his work and those individuals he supports. He has demonstrated an incredible commitment to the Department, and it is a better place because of him.”
  • Alison Salie, senior fiscal officer in the Department of Biology, was nominated by professor and department head Alan Grossman because Salie “is a top-notch employee, well-respected across the department and Institute, and valued for her knowledge and expertise, common-sense approach, willingness to provide support and guidance at every turn, persistence, and never-ending goal to keep work flowing smoothly with limited administrative burden on faculty.”
  • Amanda Trainor, a technical associate in the Department of Chemistry, was nominated by colleagues John Dolhun, Brian Pretti, Scott Ide, John Grimes, and graduate student Axel Vera because her “work on all aspects of various lab functions has been outstanding, from finishing her assigned responsibilities, to taking on unassigned work that needed to be done, [and] demonstrating a strong commitment to the well-being of the MIT community by going countless extra miles.”
  • Joshua Wolfe, a technical instructor in the Department of Physics, was nominated by postdoc Alex Shvonski and lecturer Michelle Tomasik because Wolfe “goes above and beyond his prescribed duties because he cares holistically about creating an effective learning environment in our classes.”
  • Macall Zimmerman, senior financial officer in the Department of Chemistry, was nominated by professor and department head Troy Van Voorhis and staff colleagues Richard Wilk and Tyler Brezler because Zimmerman “is someone who goes far above and beyond her usual call of duty. She is an excellent leader, manager, and mentor. She demonstrates an exceptional commitment to every aspect of her work and the staff whom she mentors. Our department is a better place with her in it.”

The 2021 Infinite Mile Award winners receive a monetary award. An in-person celebration will be held in their honor, as well as the 2021 Infinite Expansion Award winners, at a later date with their families, friends, and nominators.

Matthew Vander Heiden named director of the Koch Institute

MIT biology professor and pioneering researcher of cancer cell metabolism will succeed longtime director Tyler Jacks.

Anne Trafton | MIT News Office
April 1, 2021

Matthew Vander Heiden, an MIT professor of biology and a pioneer in the field of cancer cell metabolism, has been named the next director of MIT’s Koch Institute for Integrative Cancer Research, effective April 1.

Vander Heiden will succeed Tyler Jacks, who has served as director for more than 19 years, first for the MIT Center for Cancer Research and then for its successor, the Koch Institute.

“Matt Vander Heiden has been a part of the Koch Institute almost from the beginning,” says MIT President L. Rafael Reif. “He knows firsthand that incredible discoveries emerge when scientists and engineers come together, in one space, to collaborate and learn from each other. We are thrilled that he will be carrying forward the institute’s groundbreaking work at the frontiers of cancer research.”

The MIT Center for Cancer Research (CCR) was founded by Nobel laureate Salvador Luria in 1974, shortly after the federal government declared a “war on cancer,” with the mission of unravelling the molecular basis of cancer. Working alongside colleagues such as Associate Director Jacqueline Lees, Jacks oversaw the evolution of the CCR into the Koch Institute in 2007, as well as the construction of the institute’s new home in Building 76, completed in 2010.

“I’m very grateful for all of the wonderful things that Tyler’s leadership has led to, because I think this really positions us to build on all of those successes and move forward to do more amazing things over the next decade,” Vander Heiden says.

Vander Heiden, who became a member of the Koch Institute in 2010 and has served as an associate director since 2017, is “an excellent choice for the Koch’s next director,” Jacks says. “Matt knows the landscape of cancer research deeply. He is very well-positioned to guide our existing programs and to develop new ones that take advantage of the unique strengths at the Koch and at MIT more broadly, at the intersection of science and engineering for cancer. I am looking forward to watching him lead the Institute’s exciting next chapter.”

Over the past several decades, cancer researchers have made significant strides in their understanding of the genetic underpinnings of the disease. They’ve also identified molecular signatures that distinguish different types of tumors, leading to the development of targeted treatments for specific types of cancer.

Vander Heiden says that he sees great opportunity in the field of cancer research for making new fundamental discoveries regarding the disease, and also for translating existing knowledge into better treatments. He expects that one key area of focus in the coming years will be applying the power of machine learning and artificial intelligence to understanding cancer.

“With the MIT Schwarzman College of Computing coming online, there’s tremendous opportunity in using the rapid advances in machine learning and computer science for health care,” Vander Heiden says. “I think that’s something MIT absolutely should be a leader on, especially as it applies to cancer.”

“Matt Vander Heiden will be a wonderful director,” says Phillip Sharp, an MIT Institute Professor and a member of the Koch Institute, who chaired the search committee for the new director. “His innovative research on cancer metabolism, service as associate director, and ability to ‘think like an engineer’ has earned him deep admiration from colleagues.”

Vander Heiden, who grew up in Wisconsin, earned his bachelor’s degree, MD, and PhD from the University of Chicago. While a graduate student, he became interested in studying the abnormal metabolism seen in cancer cells, which was first discovered nearly 100 years ago by the German chemist Otto Warburg. Instead of breaking down sugar using aerobic respiration, as healthy mammalian cells do, cancer cells switch to an alternative metabolic pathway called fermentation, which is less efficient.

As a postdoc in 2008, Vander Heiden and his colleagues at Harvard Medical School made the discovery that cancer cells shift their metabolism to fermentation by activating an enzyme called PKM2. While at Harvard, Vander Heiden also worked on a paper that contributed to the eventual development of drugs that target cancer cells with a mutation in the IDH gene. These drugs, the first modern FDA-approved cancer drugs that target metabolism, shut off an alternative pathway used by cancer cells with the IDH mutation.

In 2010, Vander Heiden became one of the first new faculty members hired after the creation of the Koch Institute. The Koch Institute was formed with the mission of bringing scientists and engineers together to work on cancer problems, an experimental approach that has had great success, Vander Heiden says.

“When I look at the Koch Institute today, I don’t think of my colleagues as being scientists or engineers. I just view them as people who are asking interesting questions in cancer, trying to solve translational problems, and trying to solve basic problems,” he says. “We have broken down all these barriers, these traditional silos of fields, and I think that uniquely positions us to answer the big questions about cancer going forward.”

While serving as director, Vander Heiden plans to continue his own research program on the role of cell metabolism in the development and progression of cancer. He also plans to continue his work as a medical oncologist at Dana-Farber Cancer Institute, where he treats prostate cancer patients.

“Having a personal link to the clinic helps keep me grounded in the realities of how patients experience cancer, and hopefully that will help me be a better steward of the Koch Institute and help us have even more impact with the work that we’re doing,” he says.

Linda Griffith and Douglas Lauffenburger honored for contributions to biological engineering education

Professors awarded the National Academy of Engineering's prestigious Bernard M. Gordon Prize for Innovation in Engineering and Technology Education.

School of Engineering
March 11, 2021

The National Academy of Engineering (NAE) has announced that two MIT professors have been jointly awarded the Bernard M. Gordon Prize for Innovation in Engineering and Technology Education, the most prestigious engineering education award in the United States.

Linda G. Griffith, the School of Engineering Professor of Teaching Innovation in the Department of Biological Engineering, and Douglas A. Lauffenburger, the Ford Professor of Biological Engineering, Chemical Engineering and Biology, were recognized for their respective contributions to “the establishment of a new biology-based engineering education, producing a new generation of leaders capable of addressing world problems with innovative biological technologies,” according to an NAE statement.

“We are absolutely delighted that professors Griffith and Lauffenburger received this prestigious prize from the NAE,” says Angela Belcher, head of the Department of Biological Engineering. “Anyone who knows Doug Lauffenburger and Linda Griffith knows that educating and mentoring in engineering, particularly biological engineering, is at the core of who they are.”

Griffith and Lauffenburger spearheaded the establishment of the biological engineering discipline at MIT, which revolves around teaching students how to translate innovations in the molecular life sciences into therapeutics, and a range of non-medical products in agriculture, materials, energy, and nutrition.

“Professor Griffith and Professor Lauffenburger have made incredible contributions to education in biological engineering,” says Anantha P. Chandrakasan, dean of the MIT School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “They have both been fundamental in establishing and shaping the biological engineering curriculum at MIT, and continue to inspire current and former students in this space.”

Griffith championed the biological engineering BS degree program, while Lauffenburger focused his efforts on the graduate level. Students who have participated in the curriculum have gone on to found innovative startups, such as Gingko Bioworks.

“The award is really in recognition of the power of MIT students to create change,” says Griffith. “The creation of a new discipline of engineering was a lot of effort, but it was done in partnership with students who were brave enough to imagine what could be.”

In addition to her achievements in education, Griffith directs the Center for Gynepathology Research and has championed novel approaches in tissue engineering. She is also responsible for establishing the field of physiomimetics.

She holds more than a dozen patents, has over 200 publications, and has chaired multiple scientific conferences, including the annual TED conference-like Open Endoscopy Forum that assembles gynecology scientists, surgeons, and engineers at MIT for a weekend of talks.

Lauffenburger is affiliated with multiple biomedical organizations including the Center for Gynepathology Research, Center for Biomedical Engineering, and Koch Institute for Integrative Cancer Research at MIT. He is a past president of the Biomedical Engineering Society and currently the chair of the College of Fellows of American Institute for Medical and Biological Engineering.

Both Griffith and Lauffenburger hope that their accomplishments at MIT will help propel biological engineering forward on a global level.

“The world needs biology-based technologies to address a broad spectrum of critical challenges that have not been satisfactorily met by physics- and chemistry-based technologies,” says Lauffenburger. “Our aspiration, and expectation, is that what we’ve created here will catalyze adoption of biology-based engineering at many other institutions worldwide in the coming years.”

Established in 2001, the Gordon Prize includes a cash award of $500,000, of which Griffith and Lauffenburger will receive half. The other half will go to support biological engineering education efforts at MIT. Griffith and Lauffenburger will also each receive a gold-plated, sterling silver medal and a hand-scribed certificate.