Category: Feature

Introducing MIT HEALS, a life sciences initiative to address pressing health challenges

The MIT Health and Life Sciences Collaborative will bring together researchers from across the Institute to deliver health care solutions at scale.

Anne Trafton | MIT News
December 10, 2024

At MIT, collaboration between researchers working in the life sciences and engineering is a frequent occurrence. Under a new initiative launched last week, the Institute plans to strengthen and expand those collaborations to take on some of the most pressing health challenges facing the world.

The new MIT Health and Life Sciences Collaborative, or MIT HEALS, will bring together researchers from all over the Institute to find new solutions to challenges in health care. HEALS will draw on MIT’s strengths in life sciences and other fields, including artificial intelligence and chemical and biological engineering, to accelerate progress in improving patient care.

“As a source of new knowledge, of new tools and new cures, and of the innovators and the innovations that will shape the future of biomedicine and health care, there is just no place like MIT,” MIT President Sally Kornbluth said at a launch event last Wednesday in Kresge Auditorium. “Our goal with MIT HEALS is to help inspire, accelerate, and deliver solutions, at scale, to some of society’s most urgent and intractable health challenges.”

The launch event served as a day-long review of MIT’s historical impact in the life sciences and a preview of what it hopes to accomplish in the future.

“The talent assembled here has produced some truly towering accomplishments. But also — and, I believe, more importantly — you represent a deep well of creative potential for even greater impact,” Kornbluth said.

Massachusetts Governor Maura Healey, who addressed the filled auditorium, spoke of her excitement about the new initiative, emphasizing that “MIT’s leadership and the work that you do are more important than ever.”

“One of things as governor that I really appreciate is the opportunity to see so many of our state’s accomplished scientists and bright minds come together, work together, and forge a new commitment to improving human life,” Healey said. “It’s even more exciting when you think about this convening to think about all the amazing cures and treatments and discoveries that will result from it. I’m proud to say, and I really believe this, this is something that could only happen in Massachusetts. There’s no place that has the ecosystem that we have here, and we must fight hard to always protect that and to nurture that.”

A history of impact

MIT has a long history of pioneering new fields in the life sciences, as MIT Institute Professor Phillip Sharp noted in his keynote address. Fifty years ago, MIT’s Center for Cancer Research was born, headed by Salvador Luria, a molecular biologist and a 1975 Nobel laureate.

That center helped to lead the revolutions in molecular biology, and later recombinant DNA technology, which have had significant impacts on human health. Research by MIT Professor Robert Weinberg and others identifying cancer genes has led the development of targeted drugs for cancer, including Herceptin and Gleevec.

In 2007, the Center for Cancer Research evolved into the Koch Institute for Integrative Cancer Research, whose faculty members are divided evenly between the School of Science and the School of Engineering, and where interdisciplinary collaboration is now the norm.

While MIT has long been a pioneer in this kind of collaborative health research, over the past several years, MIT’s visiting committees reported that there was potential to further enhance those collaborations, according to Nergis Mavalvala, dean of MIT’s School of Science.

“One of the very strong themes that emerged was that there’s an enormous hunger among our colleagues to collaborate more. And not just within their disciplines and within their departments, but across departmental boundaries, across school boundaries, and even with the hospitals and the biotech sector,” Mavalvala told MIT News.

To explore whether MIT could be doing more to encourage interdisciplinary research in the life sciences, Mavalvala and Anantha Chandrakasan, dean of the School of Engineering and MIT’s chief innovation and strategy officer, appointed a faculty committee called VITALS (Vision to Integrate, Translate and Advance Life Sciences).

That committee was co-chaired by Tyler Jacks, the David H. Koch Professor of Biology at MIT and a member and former director of the Koch Institute, and Kristala Jones Prather, head of MIT’s Department of Chemical Engineering.

“We surveyed the faculty, and for many people, the sense was that they could do more if there were improved mechanisms for interaction and collaboration. Not that those don’t exist — everybody knows that we have a highly collaborative environment at MIT, but that we could do even more if we had some additional infrastructure in place to facilitate bringing people together, and perhaps providing funding to initiate collaborative projects,” Jacks said before last week’s launch.

These efforts will build on and expand existing collaborative structures. MIT is already home to a number of institutes that promote collaboration across disciplines, including not only the Koch Institute but also the McGovern Institute for Brain Research, the Picower Institute for Learning and Memory, and the Institute for Medical Engineering and Science.

“We have some great examples of crosscutting work around MIT, but there’s still more opportunity to bring together faculty and researchers across the Institute,” Chandrakasan said before the launch event. “While there are these great individual pieces, we can amplify those while creating new collaborations.”

Supporting science

In her opening remarks on Wednesday, Kornbluth announced several new programs designed to support researchers in the life sciences and help promote connections between faculty at MIT, surrounding institutions and hospitals, and companies in the Kendall Square area.

“A crucial part of MIT HEALS will be finding ways to support, mentor, connect, and foster community for the very best minds, at every stage of their careers,” she said.

With funding provided by Noubar Afeyan PhD ’87, an executive member of the MIT Corporation and founder and CEO of Flagship Pioneering, MIT HEALS will offer fellowships for graduate students interested in exploring new directions in the life sciences.

Another key component of MIT HEALS will be the new Hood Pediatric Innovation Hub, which will focus on development of medical treatments specifically for children. This program, established with a gift from the Charles H. Hood Foundation, will be led by Elazer Edelman, a cardiologist and the Edward J. Poitras Professor in Medical Engineering and Science at MIT.

“Currently, the major market incentives are for medical innovations intended for adults — because that’s where the money is. As a result, children are all too often treated with medical devices and therapies that don’t meet their needs, because they’re simply scaled-down versions of the adult models,” Kornbluth said.

As another tool to help promising research projects get off the ground, MIT HEALS will include a grant program known as the MIT-MGB Seed Program. This program, which will fund joint research projects between MIT and Massachusetts General Hospital/Brigham and Women’s Hospital, is being launched with support from Analog Devices, to establish the Analog Devices, Inc. Fund for Health and Life Sciences.

Additionally, the Biswas Family Foundation is providing funding for postdoctoral fellows, who will receive four-year appointments to pursue collaborative health sciences research. The details of the fellows program will be announced in spring 2025.

“One of the things we have learned through experience is that when we do collaborative work that is cross-disciplinary, the people who are actually crossing disciplinary boundaries and going into multiple labs are students and postdocs,” Mavalvala said prior to the launch event. “The trainees, the younger generation, are much more nimble, moving between labs, learning new techniques and integrating new ideas.”

Revolutions

Discussions following the release of the VITALS committee report identified seven potential research areas where new research could have a big impact: AI and life science, low-cost diagnostics, neuroscience and mental health, environmental life science, food and agriculture, the future of public health and health care, and women’s health. However, Chandrakasan noted that research within HEALS will not be limited to those topics.

“We want this to be a very bottom-up process,” he told MIT News. “While there will be a few areas like AI and life sciences that we will absolutely prioritize, there will be plenty of room for us to be surprised on those innovative, forward-looking directions, and we hope to be surprised.”

At the launch event, faculty members from departments across MIT shared their work during panels that focused on the biosphere, brains, health care, immunology, entrepreneurship, artificial intelligence, translation, and collaboration. The program, which was developed by Amy Keating, head of the Department of Biology, and Katharina Ribbeck, the Andrew and Erna Viterbi Professor of Biological Engineering, also included a spoken-word performance by Victory Yinka-Banjo, an MIT senior majoring in computer science and molecular biology.

In her performance, called “Systems,” Yinka-Banjo urged the audience to “zoom out,” look at systems in their entirety, and pursue collective action.

“To be at MIT is to contribute to an era of infinite impact. It is to look beyond the microscope, zooming out to embrace the grander scope. To be at MIT is to latch onto hope so that in spite of a global pandemic, we fight and we cope. We fight with science and policy across clinics, academia, and industry for the betterment of our planet, for our rights, for our health,” she said.

In a panel titled “Revolutions,” Douglas Lauffenburger, the Ford Professor of Engineering and one of the founders of MIT’s Department of Biological Engineering, noted that engineers have been innovating in medicine since the 1950s, producing critical advances such as kidney dialysis, prosthetic limbs, and sophisticated medical imaging techniques.

MIT launched its program in biological engineering in 1998, and it became a full-fledged department in 2005. The department was founded based on the concept of developing new approaches to studying biology and developing potential treatments based on the new advances being made in molecular biology and genomics.

“Those two revolutions laid the foundation for a brand new kind of engineering that was not possible before them,” Lauffenburger said.

During that panel, Jacks and Ruth Lehmann, director of the Whitehead Institute for Biomedical Research, outlined several interdisciplinary projects underway at the Koch Institute and the Whitehead Institute. Those projects include using AI to analyze mammogram images and detect cancer earlier, engineering drought-resistant plants, and using CRISPR to identify genes involved in toxoplasmosis infection.

These examples illustrate the potential impact that can occur when “basic science meets translational science,” Lehmann said.

“I’m really looking forward to HEALS further enlarging the interactions that we have, and I think the possibilities for science, both at a mechanistic level and understanding the complexities of health and the planet, are really great,” she said.

The importance of teamwork

To bring together faculty and students with common interests and help spur new collaborations, HEALS plans to host workshops on different health-related topics. A faculty committee is now searching for a director for HEALS, who will coordinate these efforts.

Another important goal of the HEALS initiative, which was the focus of the day’s final panel discussion, is enhancing partnerships with Boston-area hospitals and biotech companies.

“There are many, many different forms of collaboration,” said Anne Klibanski, president and CEO of Mass General Brigham. “Part of it is the people. You bring the people together. Part of it is the ideas. But I have found certainly in our system, the way to get the best and the brightest people working together is to give them a problem to solve. You give them a problem to solve, and that’s where you get the energy, the passion, and the talent working together.”

Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, noted the importance of tackling fundamental challenges without knowing exactly where they will lead. Langer, trained as a chemical engineer, began working in biomedical research in the 1970s, when most of his engineering classmates were going into jobs in the oil industry.

At the time, he worked with Judah Folkman at Boston Children’s Hospital on the idea of developing drugs that would starve tumors by cutting off their blood supply. “It took many, many years before those would [reach patients],” he says. “It took Genentech doing great work, building on some of the things we did that would lead to Avastin and many other drugs.”

Langer has spent much of his career developing novel strategies for delivering molecules, including messenger RNA, into cells. In 2010, he and Afeyan co-founded Moderna to further develop mRNA technology, which was eventually incorporated into mRNA vaccines for Covid.

“The important thing is to try to figure out what the applications are, which is a team effort,” Langer said. “Certainly when we published those papers in 1976, we had obviously no idea that messenger RNA would be important, that Covid would even exist. And so really it ends up being a team effort over the years.”

KI Gallery Exhibit: Artifacts from a half century of cancer research

Celebrating 50 years of MIT's cancer research program and the individuals who have shaped its journey, the Koch Institute Gallery features 10 significant artifacts, from one of the earliest PCR machine developed by Nobel Laureate H. Robert Horvitz to a preserved zebrafish from the lab of Nancy Hopkins in the Koch Institute Public Galleries. Visit Monday through Friday, 9AM-5PM.

Koch Institute
November 21, 2024

Throughout 2024, MIT’s Koch Institute for Integrative Cancer Research has celebrated 50 years of MIT’s cancer research program and the individuals who have shaped its journey. In honor of this milestone anniversary year, on November 19, the Koch Institute celebrated the opening of a new exhibition: Object Lessons: Celebrating 50 Years of Cancer Research at MIT in 10 Items. Object Lessons invites the public to explore significant artifacts—from one of the earliest PCR machines, developed in the lab of Nobel laureate H. Robert Horvitz, to Greta, a groundbreaking zebrafish from the lab of Professor Nancy Hopkins—in the half century of discoveries and advancements that have positioned MIT at the forefront of the fight against cancer.

50 years of innovation

The exhibition provides a glimpse into the many contributors and advancements that have defined MIT’s cancer research history since the founding of the Center for Cancer Research in 1974. When the National Cancer Act was passed in 1971, very little was understood about the biology of cancer, and it aimed to deepen our understanding of cancer and develop better strategies for the prevention, detection, and treatment of the disease. MIT embraced this call to action, establishing a center where many leading biologists tackled cancer’s fundamental questions. Building on this foundation, the Koch Institute opened its doors in 2011, housing engineers and life scientists from many fields under one roof to accelerate progress against cancer in novel and transformative ways.

In the 13 years since, the Koch Institute’s collaborative and interdisciplinary approach to cancer research has yielded significant advances in our understanding of the underlying biology of cancer and allowed for the translation of these discoveries into meaningful patient impacts. Over 120 spin-out companies—many headquartered nearby in the Kendall Square area—have their roots in Koch Institute research, with nearly half having advanced their technologies to clinical trials or commercial applications. The Koch Institute’s collaborative approach extends beyond its labs: principal investigators often form partnerships with colleagues at world-renowned medical centers, bridging the gap between discovery and clinical impact.

Current Koch Institute Director Matthew Vander Heiden, also a practicing oncologist at the Dana-Farber Cancer Institute, is driven by patient stories.

“It is never lost on us that the work we do in the lab is important to change the reality of cancer for patients,” he says. “We are constantly motivated by the urgent need to translate our research and improve outcomes for those impacted by cancer.”

Symbols of progress

The items on display as part of Object Lessons take viewers on a journey through five decades of MIT cancer research, from the pioneering days of Salvador Luria, founding director of the Center for Cancer Research, to some of the Koch Institute’s newest investigators including Francisco Sánchez-Rivera, Eisen and Chang Career Development Professor and an assistant professor of biology, and Jessica Stark, Underwood-Prescott Career Development Professor and an assistant professor of biological engineering and chemical engineering.

Among the standout pieces is a humble yet iconic object: Salvador Luria’s ceramic mug, emblazoned with “Luria’s broth.” Lysogeny broth, often called—apocryphally—Luria Broth, is a medium for growing bacteria. Still in use today, the recipe was first published in 1951 by a research associate in Luria’s lab. The artifact, on loan from the MIT Museum, symbolizes the foundational years of the Center for Cancer Research and serves as a reminder of Luria’s influence as an early visionary. His work set the stage for a new era of biological inquiry that would shape cancer research at MIT for generations.

Visitors can explore firsthand how the Koch Institute continues to build on the legacy of its predecessors, translating decades of knowledge into new tools and therapies that have the potential to transform patient care and cancer research.

For instance, the PCR machine designed in the Horvitz Lab in the 1980s made genetic manipulation of cells easier, and gene sequencing faster and more cost-effective. At the time of its commercialization, this groundbreaking benchtop unit marked a major leap forward. In the decades since, technological advances have allowed for the visualization of DNA and biological processes at a much smaller scale, as demonstrated by the handheld BioBits® imaging device developed by Stark and on display next door to the Horvitz panel.

 “We created BioBits kits to address a need for increased equity in STEM education,” Stark says. “By making hands-on biology education approachable and affordable, BioBits kits are helping inspire and empower the next generation of scientists.”

While the exhibition showcases scientific discoveries and marvels of engineering, it also aims to underscore the human element of cancer research through personally significant items, such as a messenger bag and Seq-Well device belonging to Alex Shalek, J. W. Kieckhefer Professor in the Institute for Medical Engineering and Science and the Department of Chemistry.

Shalek investigates the molecular differences between individual cells, developing mobile RNA-sequencing devices. He could often be seen toting the bag around the Boston area, and worldwide as he perfected and shared his technology with collaborators near and far. Through his work, Shalek has helped to make single cell sequencing accessible for labs in more than 30 countries across six continents.

“The KI seamlessly brings together students, staff, clinicians, and faculty across multiple different disciplines to collaboratively derive transformative insights into cancer,” Shalek says. “To me, these sorts of partnerships are the best part about being at MIT.”

Around the corner from Shalek’s display, visitors will find an object that serves as a stark reminder of the real people impacted by Koch Institute research: Steven Keating’s SM’12, PhD ’16 3D-printed model of his own brain tumor. Keating, who passed away in 2019, became a fierce advocate for the rights of patients to their medical data, and came to know Vander Heiden through his pursuit to become an expert on his tumor type, IDH-mutant glioma. In the years since, Vander Heiden’s work has contributed to a new therapy to treat Steven’s tumor type. In 2024, the drug, called vorasidenib, gained FDA approval, providing the first therapeutic breakthrough for Keating’s cancer in more than 20 years.

As the Koch Institute looks to the future, Object Lessons stands as a celebration of the people, the science, and the culture that have defined MIT’s first half-century of breakthroughs and contributions to the field of cancer research.

“Working in the uniquely collaborative environment of the Koch Institute and MIT, I am confident that we will continue to unlock key insights in the fight against cancer,” says Vander Heiden. “Our community is poised to embark on our next 50 years with the same passion and innovation that has carried us this far.”

Object Lessons will be on view in the Koch Institute Public Galleries. Visit Monday through Friday, 9 a.m. to 5 p.m., to see the exhibit up close.

Alumni Spotlight: Distillery Founder with a Spirited Passion

Jennifer Yang, '97, has been drawing on her biology degree for making spirits at a craft distillery in Maryland.

Jessica R. Simpson | Slice of MIT
October 15, 2024

If you had told Jennifer Yang ’97 during her time as a Course 7 major at MIT that she would use her biology degree to run a distillery, she wouldn’t have believed you.

“When I was at MIT, I looked at entrepreneurs and I thought, ‘Oh my gosh, that’s not me. I’m not one of those people who are so innovative and gutsy and brave,’” Yang says.

Managing a distillery is a passion that matured in Yang over time—much like the complex flavor of a barrel-aged whiskey. After graduating from MIT, the New York-native moved to Washington, DC, to pursue a career in management and technology consulting, which involved a lot of after-hours networking events. While building connections with colleagues over a glass of whiskey—a drink that was particularly popular with clients—Yang discovered her passion. Over the course of 10 years, she researched the science of making spirits, explored different small distilleries, and even started a whiskey tasting club.

“Being a science geek at heart and being very curious, I went down this rabbit hole pretty quickly in terms of wanting to learn more about it,” Yang explains.

In November 2022, she and her husband opened Covalent Spirits, a craft distillery, tasting room, and event space in Westminster, Maryland. In addition to producing bourbon whiskey, Covalent Spirits distills and blends vodka, gin, rum, and liqueurs. One of the bar’s unique and in-demand offerings is the “pH,” or “power of hydrogen,” cocktail, which uses the acidity of lemonade to turn a blue tea into a vibrant purple. Yang still works in consulting, but you can find her in her element behind the bar, engineering “pH” (and many other) cocktails Thursday through Saturday.

In her spare time, Yang is a committed MIT volunteer. An active participant in the Club of Washington DC, she is the regional alumni ambassador for the Baltimore area as well. Yang is also an educational counselor and the current president of the Class of 1997. She notes that she and her ’97 classmates were the first to organize pi reunions, a tradition in which alums gather in Las Vegas 3.14 years after graduation. “We’re glad our class could leave a little bit of a legacy,” she says.

In fact, the shared MIT connection between alumni inspired Yang to name her company Covalent Spirits. One year, at an MIT gathering, Yang started talking to another alum about planning events for undergrad classes that shared years at MIT—what they called “covalent classes.” Yang has since incorporated literal and metaphorical covalent bonds (a chemical connection between atoms formed by sharing) into every facet of her business: from the chemistry of making spirits, to the design of the distillery logo, to the company’s emphasis on community.

“While we are striving to create really good products, we also want to create a space and experiences for people to get together and geek out over a common interest, to celebrate an occasion, or to connect over anything,” Yang elaborates. “You share a drink, you share an experience, you share a community. Bonding through sharing is the covalent spirit.”

A new approach to modeling complex biological systems

MIT engineers’ new model could help researchers glean insights from genomic data and other huge datasets. This is potentially critical to researchers who study any kind of complex biological system, according to senior author Douglas Lauffenburger.

Anne Trafton | MIT News
November 5, 2024

Over the past two decades, new technologies have helped scientists generate a vast amount of biological data. Large-scale experiments in genomics, transcriptomics, proteomics, and cytometry can produce enormous quantities of data from a given cellular or multicellular system.

However, making sense of this information is not always easy. This is especially true when trying to analyze complex systems such as the cascade of interactions that occur when the immune system encounters a foreign pathogen.

MIT biological engineers have now developed a new computational method for extracting useful information from these datasets. Using their new technique, they showed that they could unravel a series of interactions that determine how the immune system responds to tuberculosis vaccination and subsequent infection.

This strategy could be useful to vaccine developers and to researchers who study any kind of complex biological system, says Douglas Lauffenburger, the Ford Professor of Engineering in the departments of Biological Engineering, Biology, and Chemical Engineering.

“We’ve landed on a computational modeling framework that allows prediction of effects of perturbations in a highly complex system, including multiple scales and many different types of components,” says Lauffenburger, the senior author of the new study.

Shu Wang, a former MIT postdoc who is now an assistant professor at the University of Toronto, and Amy Myers, a research manager in the lab of University of Pittsburgh School of Medicine Professor JoAnne Flynn, are the lead authors of a new paper on the work, which appears today in the journal Cell Systems.

Modeling complex systems

When studying complex biological systems such as the immune system, scientists can extract many different types of data. Sequencing cell genomes tells them which gene variants a cell carries, while analyzing messenger RNA transcripts tells them which genes are being expressed in a given cell. Using proteomics, researchers can measure the proteins found in a cell or biological system, and cytometry allows them to quantify a myriad of cell types present.

Using computational approaches such as machine learning, scientists can use this data to train models to predict a specific output based on a given set of inputs — for example, whether a vaccine will generate a robust immune response. However, that type of modeling doesn’t reveal anything about the steps that happen in between the input and the output.

“That AI approach can be really useful for clinical medical purposes, but it’s not very useful for understanding biology, because usually you’re interested in everything that’s happening between the inputs and outputs,” Lauffenburger says. “What are the mechanisms that actually generate outputs from inputs?”

To create models that can identify the inner workings of complex biological systems, the researchers turned to a type of model known as a probabilistic graphical network. These models represent each measured variable as a node, generating maps of how each node is connected to the others.

Probabilistic graphical networks are often used for applications such as speech recognition and computer vision, but they have not been widely used in biology.

Lauffenburger’s lab has previously used this type of model to analyze intracellular signaling pathways, which required analyzing just one kind of data. To adapt this approach to analyze many datasets at once, the researchers applied a mathematical technique that can filter out any correlations between variables that are not directly affecting each other. This technique, known as graphical lasso, is an adaptation of the method often used in machine learning models to strip away results that are likely due to noise.

“With correlation-based network models generally, one of the problems that can arise is that everything seems to be influenced by everything else, so you have to figure out how to strip down to the most essential interactions,” Lauffenburger says. “Using probabilistic graphical network frameworks, one can really boil down to the things that are most likely to be direct and throw out the things that are most likely to be indirect.”

Mechanism of vaccination

To test their modeling approach, the researchers used data from studies of a tuberculosis vaccine. This vaccine, known as BCG, is an attenuated form of Mycobacterium bovis. It is used in many countries where TB is common but isn’t always effective, and its protection can weaken over time.

In hopes of developing more effective TB protection, researchers have been testing whether delivering the BCG vaccine intravenously or by inhalation might provoke a better immune response than injecting it. Those studies, performed in animals, found that the vaccine did work much better when given intravenously. In the MIT study, Lauffenburger and his colleagues attempted to discover the mechanism behind this success.

The data that the researchers examined in this study included measurements of about 200 variables, including levels of cytokines, antibodies, and different types of immune cells, from about 30 animals.

The measurements were taken before vaccination, after vaccination, and after TB infection. By analyzing the data using their new modeling approach, the MIT team was able to determine the steps needed to generate a strong immune response. They showed that the vaccine stimulates a subset of T cells, which produce a cytokine that activates a set of B cells that generate antibodies targeting the bacterium.

“Almost like a roadmap or a subway map, you could find what were really the most important paths. Even though a lot of other things in the immune system were changing one way or another, they were really off the critical path and didn’t matter so much,” Lauffenburger says.

The researchers then used the model to make predictions for how a specific disruption, such as suppressing a subset of immune cells, would affect the system. The model predicted that if B cells were nearly eliminated, there would be little impact on the vaccine response, and experiments showed that prediction was correct.

This modeling approach could be used by vaccine developers to predict the effect their vaccines may have, and to make tweaks that would improve them before testing them in humans. Lauffenburger’s lab is now using the model to study the mechanism of a malaria vaccine that has been given to children in Kenya, Ghana, and Malawi over the past few years.

“The advantage of this computational approach is that it filters out many biological targets that only indirectly influence the outcome and identifies those that directly regulate the response. Then it’s possible to predict how therapeutically altering those biological targets would change the response. This is significant because it provides the basis for future vaccine and trial designs that are more data driven,” says Kathryn Miller-Jensen, a professor of biomedical engineering at Yale University, who was not involved in the study.

Lauffenburger’s lab is also using this type of modeling to study the tumor microenvironment, which contains many types of immune cells and cancerous cells, in hopes of predicting how tumors might respond to different kinds of treatment.

The research was funded by the National Institute of Allergy and Infectious Diseases.

Research Reflections: Alison Biester (PhD ’24), Drennan Lab

New snapshots of ancient life

Alison Biester | Department of Chemistry
October 3, 2024

The resolution revolution, beating “blobology”, and shedding light on how ancient microbes thrived in a primordial soup.

The earliest life on earth created biological molecules despite the limited materials available in the primordial soup such as CO2, hydrogen gas, and minerals containing iron, nickel, and sulfur.

As ancient microbes evolved, they developed proteins that sped up chemical reactions, called enzymes. Enzymes were evolutionarily advantageous because they created local environments called active sites optimized for reaction performance.

Although we know that carbon is the building block of life on earth–we wouldn’t exist without carbon-based molecules such as proteins and DNA–much remains unclear about how more complex carbon-based molecules were originally generated from CO2. Proteins and DNA are huge molecules with thousands of carbon atoms, so creating life from CO2 would be no small undertaking.

Catherine Drennan, Professor of Biology and Chemistry and HHMI Investigator and Professor, has long studied the enzymes that perform these crucial reactions wherein CO2 is converted into a form of carbon that cells can use, which requires iron, nickel, and sulfur.

In particular, she uses structural biology to study carbon monoxide dehydrogenase (CODH), which reacts with CO2 to produce CO, and acetyl-CoA synthase (ACS), which uses CO with another single unit of carbon to create a carbon-carbon bond. Crystallographic work by Drennan and others has provided structural snapshots of bacterial CODH and ACS, but its structure in other contexts remains elusive. During my PhD, I worked with Drennan on the structural characterization of CODH and ACS, culminating in a publication in PNAS, published October 3, 2024.

Throughout Drennan’s career, the lab has used a method known as X-ray crystallography to determine enzyme structures at atomic resolution. In recent years, however, cryogenic electron microscopy (cryo-EM) has risen in popularity as a structural biology technique.

Cryo-EM offers some key advantages over X-ray crystallography, such as its ability to capture structures of large and dynamic complexes. However, cryo-EM is limited in its ability to elucidate structures of small proteins, an area where X-ray crystallography continues to excel.

To perform a cryo-EM experiment, proteins are rapidly frozen in a thin layer of ice and imaged on an electron microscope. By capturing images of the protein in various orientations, researchers can generate a 3D model of their protein of interest.

Around 2015, cryo-EM reached a tipping point known as the “resolution revolution.” Due to improvements in both the hardware for collecting cryo-EM data and the software used for data processing, the technique could, for the first time, be used to determine protein structures at near-atomic resolution.

Seeing the potential for this new technique, MIT opened its very own cryo-EM facility with two electron microscopes in 2018. Just a year later, I joined the Drennan lab. When I began my thesis work, Cathy asked “Would you like to do crystallography or cryo-EM?”

Eager to try something that was both novel for researchers and new to me, I chose cryo-EM.

Ancient microbes

An ancient type of microbe, archaea, also uses CODH and ACS. Without information on how these protein chains interact, we cannot understand how these proteins work together within this complex–but it’s a difficult question to answer. In total, the complex contains forty protein chains that interact with one another and adopt various conformations to perform their chemistry.

We don’t know for sure which ACS enzyme came first, the bacterial or archaeal one, but we know they are both very ancient.

Archaeal CODH has been visualized via X-ray crystallography, but that CODH was isolated from the enormous megadalton enzyme complex present in the native archaea.

A CO2 molecule, which reacts with CODH, is 44 daltons; the enzyme complex at 2.2 megadaltons is 50,000 times the size of CO2. The complex consists of several copies of CODH, ACS, and a cobalt-containing enzyme that donates the second one-carbon unit used by ACS. Due to the large and dynamic nature of the complex, it was a great candidate for visualizing with cryo-EM.

Before I joined the lab, a collaboration had been initiated between the Drennan Lab and Dr. David Grahame of the Uniformed Services University of the Health Sciences, an expert in archaeal CODH and ACS.

Just before his retirement, Grahame grew hundreds of liters of archaea and isolated approximately one gram of the enzyme complex that he provided to the Drennan Lab for structural characterization. Each cryo-EM experiment can use as little as a microgram of protein. For a structural biologist, having one gram of protein–in theory, enough for one million experiments–to work with is a dream.

Blobology

With an abundance of protein, I embarked on this project with this exciting new technique on a promising target. I prepared my cryo-EM sample and collected data at the new MIT cryo-EM facility. As I was collecting data, I could see in the images large protein complexes that appeared to be my complex of interest. I could also see some smaller proteins that were consistent with the shape of isolated CODH. When I went on to process my data, I focused on the larger protein complexes, since the structure of isolated CODH was already known.

However, when I finished processing my first dataset, I was a bit disappointed. My resolution was very low–instead of atoms, I was seeing amorphous blobs, and I had no idea which blob matched with which protein, or how the proteins fit together. Rather than post-revolution cryo-EM, I felt like I was performing the “blobology” of the past.

Our cryo-EM data contains detailed structural information that becomes evident after significant data processing. On the left is the initial structure of our proteins of interest, carbon monoxide dehydrogenase (CODH) and acetyl-CoA synthase (ACS), and on the right is our final, detailed one. Photo courtesy of Alison Biester.

But the project was young, and a few failed experiments are par for the course of a PhD.

The next step was sample optimization, and luckily I had plenty of sample to work with. I tried preparing the protein in a different way, changed the protein concentration, used different additives, and scaled up my data collection.

Nothing helped. No matter what I tried, I could not move out of blobology territory. So, as one does when a project is failing, I stepped away. I worked on other projects and stopped thinking about the archaeal CODH and ACS.

A few months later, the cryo-EM facility was seeking users to try a new sample preparation instrument called the chameleon. Chameleon automates the sample preparation process and is intended to improve sample quality. With plenty of sample still to spare, I volunteered to try the instrument.

Just prior to my data collection, the facility had also installed a new software that allows data processing as it is being collected. The software uses automated processes to select proteins within your data; previously, I had only selected large protein complexes consistent with my complex of interest after the fact.

The new software is not very discriminating–but I was surprised when I looked at the results of the live processing. The processing showed that I had a protein complex in my sample that I did not expect – a complex of CODH and ACS!

This complex had just one copy of CODH and one copy of ACS, unlike the full complex that has multiple copies of each. My excitement for the project was reinvigorated. With this new target, could I leave blobology behind and finally join the resolution revolution?

After running more experiments and collecting more data and a few months of data processing, I realized that the sample contained three different states: isolated CODH, CODH with one copy of ACS, and CODH with two copies of ACS. I was able to use the Model-based Analysis of Volume Ensembles (MAVEn) tool developed by the Davis Lab at MIT to sort out these three states. When I finished the data processing, I achieved near-atomic resolution of all three states.

Through this work, for the first time, we can see what the archaeal ACS looks like. The archaeal ACS is fundamentally different from the bacterial one: a huge portion of the enzyme is missing, including part of the enzyme that makes up the active site in bacteria, leaving open the question of what the ACS active site looks like in archaea.

In our structure of archaeal ACS in complex with CODH, we were surprised to see that the active site looks almost identical to the bacterial one. This similarity is enabled by the archaeal CODH, which compensates for the missing part of ACS.

Given how similar the ACS active site environment in bacterial and archaea, we are likely getting a look at an active site that has remained conserved over billions of years of evolution.

Although the project didn’t fulfill its original promise of solving the structure of the large, dynamic protein complex, I did find intriguing insights. The tools available in 2015 would not have enabled me to achieve these results; it is clear to me that the resolution revolution is far from over, and the evolution of structural biology has been fascinating to experience. Cryo-EM has and will continue to evolve, as amazing new tools are still being developed.

Since graduating from MIT, I’ve been working at the Protein Data Bank, the data center that houses all available protein structure information. Working here gives me a front-row view of new discoveries in structural biology. I’m so excited to see where this field will go in the future.

BSG-MSRP-Bio Student Profile: Adriana Camacho-Badillow, Calo Lab

Understanding the Role of PARPs and UBF1 in Building Ribosomes

Noah Daly | Department of Biology
September 25, 2024

While pursuing her passion for research, BSG-MSRP-Bio student Adriana Camacho-Badillo made major contributions to research in the Calo Lab in the Department of Biology at MIT.

Growing up in Puerto Rico, Adriana Camacho-Badillo had no explanation for her recurrent multiple fracture injuries. In her teens, she was finally able to see a geneticist who diagnosed her with a genetic syndrome that affects connective tissue throughout the body. 

This awakened an interest in genetics that led her to immerse herself in her genetic panel results, curious about the role of each gene that was tested. 

“I realized I wanted to find out how mutations affect gene expression that could possibly lead to a distinct phenotype or even a genetic syndrome,” she says. 

Within a few years of setting her sights on becoming a scientist, Camacho-Badillo began her first research experience working in the laboratory of Professors Hector Areizaga-Martínez and Elddie Román-Morales. Her work focused on experiments using enzymes to degrade Dichloro-diphenyl-trichloroethane, or DDT, a once-common pesticide known to be highly toxic to humans and other mammals that remains in the environment long after application to crops. 

As she became familiar with the day-to-day routines of designing and executing research experiments, she realized she was drawn to biochemistry and molecular biology. Camacho-Badillo soon applied to the molecular neuroscience lab of Professor Miguel Méndez at the University of Puerto Rico at Aguadilla and joined their team working on the effects of high glucose in the central nervous system of mice.

Expanding Experiences While Narrowing Focus

When Camacho-Badillo was sixteen, alongside Méndez and other students, she participated in the Quantitative Methods Workshop at MIT. The workshop allows undergraduate students from universities around the United States and the Caribbean to come together for a few days in January to learn how to apply computational tools that can help biological research. 

One of the sessions she attended was a talk about machine learning and studying the brain, presented by graduate student Taylor Baum. 

“I loved Taylor’s workshop,” Camacho-Badillo said, “When Taylor asked if anyone would be interested in volunteering to teach Spanish-speaking students in grade school science, I said yes without hesitation.” 

Baum, a neuroscientist and computer scientist working in the Munther Dahleh Research Group at MIT, is also the founder of Sprouting, Inc. The organization equips high-school students and undergraduates in Puerto Rico with STEM skills to help them pursue careers in science and technology.

After participating in QMW, it wasn’t long before Camacho-Badillo was back at MIT. She participated in the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology in 2023 and worked in the Yamashita Lab, studying two phenotypes of genetic mutations associated with cancer during cell division. 

The BSG-MSRP-Bio program offers lab experience and extracurricular activities such as journal clubs and dinners with professors. At one of these events, she met Associate Professor of Biology Eliezer Calo.

Camacho-Badillo and her mentor Eliezer Calo, Associate Professor of Biology. Photo Credit: Mandana Sassanfar.

“I loved meeting another scientist from Puerto Rico working on molecular biology, so I decided to look further into his research,” Camacho-Badillo recalls. 

In 2024, she was delighted to have the opportunity to return to the BSG-MSRP-Bio Program for a second time, and now to work in Calo’s Lab. 

The Unsolved Mysteries of UBF1

Although BSG-MSRP-Bio students are often mentored by graduate students or postdocs, Calo spent the summer mentoring Camacho-Badillo directly. As an alumnus of the MSRP-Bio program himself, Calo understands firsthand how much of an impact meaningful research can have for an undergraduate student spending a few months experiencing life in the lab at MIT. 

In the Calo Lab, Camacho-Badillo spent the early days of this summer poring over past research papers on genetic transcription, trying to answer a big question in molecular biology. Camacho-Badillo has been helping Calo understand how a particular protein affects the production of ribosomes in cells.

A ribosome is the molecular machinery that synthesizes proteins, and an average cell can produce around 10 million ribosomes to sustain its essential functions. Creating these protein engines requires the transcription of ribosomal DNA, or rDNA. 

In order to synthesize RNA, specific proteins called polymerases must bind to the DNA. Camacho-Badillo’s work focuses on one of those binding proteins called upstream binding factor, or UBF1. UBF1 is essential for the synthesis of the ribosomal RNA. The UBF1 transcription factor is responsible for recruiting the polymerase, RNA polymerase I, to transcribe the rDNA into rRNA.

Despite knowing the importance of UBF1 in ribosomal production, it’s unclear what its full purpose is in this process. Calo and Camacho-Badillo think that clarifying the role of UBF1 in ribosomal biogenesis will help scientists understand how certain neurological diseases occur. UBF1 is known to be associated with diseases such as acute myeloid leukemia and childhood-onset neurodegeneration with brain atrophy, but the mechanism is not yet understood.

UBF1 is a peculiar transcription factor. Before it can transcribe a gene, UBF1 must first dimerize, forming a bond with another UBF1 protein. After binding to the rDNA, UBF1 can recruit the remaining RNA transcription machinery. The dimer is crucial for transcription to occur, yet this protein can make further connections with other UBF1 monomers, a process called oligomerization. 

Nothing is concretely understood about how oligomers of UBF1 form: they could be critical for transcription, forming clusters that can no longer bind with rDNA or inhibit the recruitment of the remaining RNA transcription machinery. These clusters could also be directly contributing to a variety of neurological diseases.

“The genome contains multiple rDNA copies, but not all are utilized,” Calo explains. “UBF1 must precisely identify the correct copies to activate while avoiding the formation of aggregates that could impair its function.”

The regulation of these dimers is also a mystery. Early in the summer, Camacho-Badillo helped make an important connection: prior research from the Calo Lab showed that enzymes called poly ADP-ribose polymerases, or PARPs, play a role in maintaining chemical properties in the nucleolus, where ribosomes are produced and assembled. The main target of these proteins within the RNA transcriptional machinery before transcription is initiated is UBF1.  

Based on this initial result, Camacho-Badillo’s entire summer project shifted to further characterize PARPs in ribosome biogenesis.

“This observation about the role PARPs plays is a big deal for us,” Calo says. “We do many experiments in my lab, but Adriana’s work this summer has opened a key gateway to understanding the mysteries behind UBF1 regulation, leading to proper ribosome production and allowing the Calo lab to pursue this goal. She’s going to be a superstar.” 

Camacho-Badillo’s work hasn’t ended with the BSG-MSRP-Bio program, however. She’ll spend the fall semester at MIT, continuing to work on understanding how rDNA transcription is regulated as a visiting student in the Calo Lab. Although she still has a year and a half to go in her undergraduate degree, she’s already set her sights on graduate school. 

“This program has meant so much to me and brought so much into my life,” she says. “All I want to do right now is keep this research going.”

Want to know more about our BSG-MSRP-Bio Students? Read more testimonials and stories here.

From open education learners to MIT coders

MIT Digital Learning Lab’s high school interns gain professional experience working on the backend of open online MITx courses. The program emerged after Mary Ellen Wiltrout, PhD '09, digital learning scientist at MIT Open Learning, connected with the executive director and founder of Empowr, a nonprofit that serves low-income communities by creating a school-to-career pipeline through software development skills.

Katherine Ouellette | MIT Open Learning
August 26, 2024

Switching programming languages is not as simple as switching word processors. Yet high schooler Thomas Esayas quickly adapted from Swift to Python during his 2023 internship with the MIT Digital Learning Lab, a joint program between MIT Open Learning and the Institute’s academic departments. One year later, Esayas returns to the Institute for a second internship and as a new undergraduate student.

“I felt thoroughly challenged and learned a lot of new skills,” says Esayas.

Through this remote opportunity, interns gain real-world coding experience and practice professional skills by collaborating on MIT’s open online courses. The four interns from Digital Learning Lab’s 2023 and 2024 cohorts also participate in Empowr, a four-year program for low-income high school students that teaches in-demand software development skills and helps them secure paid internships.

The Digital Learning Lab program emerged after Mary Ellen Wiltrout PhD ’09, digital learning scientist at MIT Open Learning, connected with Adrian Devezin, executive director and founder of Empowr, at a conference about making education more accessible and equitable.

“It was affirming to have someone else see what Empowr is trying to do,” says Devezin about the organization’s goal to strengthen the school-to-career pipeline. “Being able to collaborate was beautiful for me, and more importantly, to the students.”

Building technical skills and self-confidence

The Digital Learning Lab internship empowers students to build confidence in their technical abilities, career skills, and the college application process. Interns assist the lab’s digital learning scientists with their work developing and maintaining online MITx courses at Open Learning across multiple academic areas.

“I found myself always busy with something interesting to work on,” says Esayas.

The interactive open education resources that Esayas produced last summer are now being used in live courses. He also helped find and fix bugs on the platform that hosts the MITx courses.

The internship’s flexible design allows projects to be adapted based on the student’s personal progress and interests.

“The students became co-creators of their educational experiences,” says Wiltrout, noting this is beneficial from a pedagogical standpoint.

Devezin adds, “I definitely saw a big improvement in their problem-solving abilities. Having to switch their mindset to a new language, work in new frameworks, and work on teams solving real problems enhanced their ability to adapt to new situations.”

The students’ also strengthened their professional repertoire in areas such as collaboration, communication, and project management. The 2023 cohort, Devezin says, developed the initiative to help other students and take on leadership roles.

Now that Esayas has completed his 2024 internship, he says, “I’m glad that I got to collaborate with more people and work on more projects. Overall, I’m very happy I was able to return.”

two people smiling, standing in front of a colorful wall.
Adrian Devezin, executive director and founder of Empowr (left), and Mary Ellen Wiltrout, digital learning scientist at MIT Open Learning (right), presented their takeaways from the first year of the MIT Digital Learning Lab internship at the 2024 Open edX conference. Photo courtesy of Empowr.

Learning from both sides

Learning occurred for both students and educators alike. Wiltrout says that the Digital Learning Lab values the opportunity to see the interns’ growth day-to-day and week-to-week, since digital learning scientists rarely follow the trajectory of individual learners who are using the course materials they create. Having instant feedback informs how they can adjust their teaching approaches for various problems.

The positive impact of the Digital Learning Lab internship’s hands-on learning experiences has made Devezin rethink the way he teaches class moving forward, and “the problems I want them to be solving,” he says.

Now, Devezin tries to emulate the real-world experience of working on a project for his Empowr students. Instead of assigning coding exercises where he provides the exact methods to solve the problems, he started asking students to determine the correct approach on their own.

The fact that Wiltrout and Devezin are open to adapting their teaching methods based on student feedback is indicative of a key factor to the internship’s success — active participation in students’ growth. It was mutually beneficial for the students and the educators to have determined stakeholders at both Digital Learning Lab and Empowr.

“A lot of dedicated educators understand that there’s a lot of inequities in education, and we need to come together to solve them,” Devezin says.

The Digital Learning Lab internship shows how open source learning materials can make educational and professional opportunities more accessible. The 2024 cohort has been able to increase their annual household income by an average of 75%, a recent Empowr report revealed. Wiltrout says that the two new Empowr students seem more confident with coding and showed enthusiasm and dedication to their tasks as they also consider colleges.

Wiltrout and Devezin presented their takeaways from the internship’s first year at the 2024 Open edX conference.

“I think it’s important to try making sure that more people are aware of tools and resources that are out there,” Wiltrout says. “Then giving people opportunities where they may not have otherwise had that chance.”

Now, Devezin is thinking about how Empowr students can come full circle with their relationship to open educational materials. He’s asking, “How can I help my students contribute to the open source world to give back to others?”

Lessons in building the future of teaching and learning

Nine shifts in pedagogical and learning approaches since the global pandemic.

Yvonne Ng | MIT Open Learning
August 7, 2024

The Covid-19 pandemic created radical shifts in approaches to teaching and learning. And while the social, emotional, and mental toll of the pandemic has diminished greatly over the last four years, residual challenges still remain for students and educators. Mary Ellen Wiltrout PhD ’09, director of online and blended learning initiatives, lecturer, and digital learning scientist in Biology at MIT, has identified these shifts in her article, “How to build the future of teaching and learning while growing from the changes and challenges of 2020–21.”

In her article, published in 2022 in Advances in Online Education: A Peer-Reviewed Journal, Wiltrout hypothesized on the lasting impacts of the 2020–2021 events on teaching and learning organized across seven themes: course logistics, tools, activities and assessment for learning, student services and programs, work culture, attitudes, and relationships. Now in 2024 at MIT, Wiltrout can see the positive changes continuing and progressing in these areas:

Flexibility: During the pandemic, instructors were more flexible about coursework requirements, scheduling, grading structure, and expanded the number and types of assignments beyond summative exams. Some enacted policies enabling partial flexibility such as dropping the lowest score on assignments or allowing for late submissions. Now, with student support services approval, instructors remain open to working with students in need of flexibility.

Online learning: Residential colleges relying on completely in-person education now incorporate more blended learning and online courses for students interested in that option. Hybrid instruction and online assignments continue to be part of the curriculum.

Technology: The most valuable functions of the learning management system are the organization of course events and materials and the integration of the multitude of learning tools in one place with one login (for example, web conferencing, discussion forum, grading, video, and calendar). As a result of reducing barriers, more tools like online conferencing, polling, and tablet drawing software to teach, are being used by a larger percentage of teaching staff and students.

Reducing unconscious bias: Grading exams and assignments through an online tool increased the efficiency and consistency of grading with rubrics for every question. And the ability to anonymize submissions in the grading process helps reduce unconscious biases, while students also gain transparency from the rubrics to learn from mistakes and trust the process.

Rethinking in-person sessions: More conversations emerged on how to take advantage of in-person interactions to prioritize activities of value in that mode for learning and work. Instructors and students intentionally kept online approaches that enriched the experience as students returned to campuses. Some digital components enhance student learning, mental well-being, equity, or inclusion and could be as easy as providing a course chat channel for peer-to-peer and peer-to-staff conversations during synchronous sessions. Some instructors maintained more creative, open-ended assignments and online exam policies that seemed experimental during 2020.

Demand for student support services: The effects of the pandemic combined with normalizing taking care of mental health resulted in the sustained high demand for student support services. Institutions continue to invest more in the staffing of these services and programs, such as peer mentoring programs that result in positive academic and attitudinal gains for students. Instructors are generally more aware of how to positively influence students to seek help with simple actions, like speaking in a warm tone and intentionally including a statement about student services.

Belonging and inclusion: Racial and social injustices are being addressed more openly than ever before. Many institutions are recognizing the value and importance of diversity, equity, and inclusion in their students and staff and have invested in funding and training for their community to shift their culture in a positive way. At the course level, instructors have the training and resources available to learn how to become more inclusive teachers (through free resources such as massive open online courses or internal efforts) and have the student and institution pressure to do so.

Mentoring: With the help of online tools and technology, students, educators, and staff are able to foster and create meaningful internship programs. Mentoring in these online programs with students in disparate locations around the world continues to take place and have a positive impact for students and any research that may be part of a program.

Collaborations: Although possible before, more researchers see collaborations across states or countries as less of a hurdle, especially with the everyday use of tools like Zoom. Instructors enhance authentic experiences for students by bringing outside experts into the classroom virtually for discussion — a method that was not used often before the pandemic.

Wiltrout concludes that many opportunities for widespread maintenance of practices that worked well and benefited students during the pandemic can and should continue to persist and grow into the future. Instructors also expanded and improved their curricula and pedagogical approaches to nurture a more inclusive and engaging course for their students and themselves.

“The lasting impacts of the pandemic include profound lessons on what best served both learners and educators,” Wiltrout says. “It’s heartening to see changes and adjustments to pedagogy, student services and programs, attitudes, and relationships that continue to benefit everyone. If these new effective ways endure and grow, then a better future of education for students, staff, and instructors is possible.”

Improving biology education here, there, and everywhere

At the cutting edge of pedagogy, Mary Ellen Wiltrout has shaped blended and online learning at MIT and beyond.

Samantha Edelen | Department of Biology
September 18, 2024

When she was a child, Mary Ellen Wiltrout PhD ’09 didn’t want to follow in her mother’s footsteps as a K-12 teacher. Growing up in southwestern Pennsylvania, Wiltrout was studious with an early interest in science — and ended up pursuing biology as a career.

But following her doctorate at MIT, she pivoted toward education after all. Now, as the director of blended and online initiatives and a lecturer with the Department of Biology, she’s shaping biology pedagogy at MIT and beyond.

Establishing MOOCs at MIT

To this day, E.C. Whitehead Professor of Biology and Howard Hughes Medical Institute (HHMI) investigator emeritus Tania Baker considers creating a permanent role for Wiltrout one of the most consequential decisions she made as department head.

Since launching the very first MITxBio massive online open course 7.00x (Introduction to Biology – the Secret of Life) with professor of biology Eric Lander in 2013, Wiltrout’s team has worked with MIT Open Learning and biology faculty to build an award-winning repertoire of MITxBio courses.

MITxBio is part of the online learning platform edX, established by MIT and Harvard University in 2012, which today connects 86 million people worldwide to online learning opportunities. Within MITxBio, Wiltrout leads a team of instructional staff and students to develop online learning experiences for MIT students and the public while researching effective methods for learner engagement and course design.

“Mary Ellen’s approach has an element of experimentation that embodies a very MIT ethos: applying rigorous science to creatively address challenges with far-reaching impact,” says Darcy Gordon, instructor of blended and online initiatives.

Mentee to motivator

Wiltrout was inspired to pursue both teaching and research by the late geneticist Elizabeth “Beth” Jones at Carnegie Mellon University, where Wiltrout earned a degree in biological sciences and served as a teaching assistant in lab courses.

“I thought it was a lot of fun to work with students, especially at the higher level of education, and especially with a focus on biology,” Wiltrout recalls, noting she developed her love of teaching in those early experiences.

Though her research advisor at the time discouraged her from teaching, Jones assured Wiltrout that it was possible to pursue both.

Jones, who received her postdoctoral training with late Professor Emeritus Boris Magasanik at MIT, encouraged Wiltrout to apply to the Institute and join American Cancer Society and HHMI Professor Graham Walker’s lab. In 2009, Wiltrout earned a PhD in biology for thesis work in the Walker lab, where she continued to learn from enthusiastic mentors.

“When I joined Graham’s lab, everyone was eager to teach and support a new student,” she reflects. After watching Walker aid a struggling student, Wiltrout was further affirmed in her choice. “I knew I could go to Graham if I ever needed to.”

After graduation, Wiltrout taught molecular biology at Harvard for a few years until Baker facilitated her move back to MIT. Now, she’s a resource for faculty, postdocs, and students.

“She is an incredibly rich source of knowledge for everything from how to implement the increasingly complex tools for running a class to the best practices for ensuring a rigorous and inclusive curriculum,” says Iain Cheeseman, the Herman and Margaret Sokol Professor of Biology and associate head of the biology department.

Stephen Bell, the Uncas and Helen Whitaker Professor of Biology and instructor of the Molecular Biology series of MITxBio courses, notes Wiltrout is known for staying on the “cutting edge of pedagogy.”

“She has a comprehensive knowledge of new online educational tools and is always ready to help any professor to implement them in any way they wish,” he says.

Gordon finds Wiltrout’s experiences as a biologist and learning engineer instrumental to her own professional development and a model for their colleagues in science education.

“Mary Ellen has been an incredibly supportive supervisor. She facilitates a team environment that centers on frequent feedback and iteration,” says Tyler Smith, instructor for pedagogy training and biology.

Prepared for the pandemic, and beyond

Wiltrout believes blended learning, combining in-person and online components, is the best path forward for education at MIT. Building personal relationships in the classroom is critical, but online material and supplemental instruction are also key to providing immediate feedback, formative assessments, and other evidence-based learning practices.

“A lot of people have realized that they can’t ignore online learning anymore,” Wiltrout noted during an interview on The Champions Coffee Podcast in 2023. That couldn’t have been truer than in 2020, when academic institutions were forced to suddenly shift to virtual learning.

“When Covid hit, we already had all the infrastructure in place,” Baker says. “Mary Ellen helped not just our department, but also contributed to MIT education’s survival through the pandemic.”

For Wiltrout’s efforts, she received a COVID-19 Hero Award, a recognition from the School of Science for staff members who went above and beyond during that extraordinarily difficult time.

“Mary Ellen thinks deeply about how to create the best learning opportunities possible,” says Cheeseman, one of almost a dozen faculty members who nominated her for the award.

Recently, Wiltrout expanded beyond higher education and into high schools, taking on several interns in collaboration with Empowr, a nonprofit organization that teaches software development skills to Black students to create a school-to-career pipeline. Wiltrout is proud to report that one of these interns is now a student at MIT in the class of 2028.

Looking forward, Wiltrout aims to stay ahead of the curve with the latest educational technology and is excited to see how modern tools can be incorporated into education.

“Everyone is pretty certain that generative AI is going to change education,” she says. “We need to be experimenting with how to take advantage of technology to improve learning.”

Ultimately, she is grateful to continue developing her career at MIT biology.

“It’s exciting to come back to the department after being a student and to work with people as colleagues to produce something that has an impact on what they’re teaching current MIT students and sharing with the world for further reach,” she says.

As for Wiltrout’s own daughter, she’s declared she would like to follow in her mother’s footsteps — a fitting symbol of Wiltrout’s impact on the future of education.

Transforming Veterans’ Lives, One Kidney Transplant at a Time

When Reynold I. Lopez-Soler, SB ’94, saw his first kidney transplant, during his medical residency, he found his life’s work.

Kathryn M. O'Neill | MIT Technology Review
September 6, 2024

When Reynold I. Lopez-Soler ’94 saw his first kidney transplant, during his medical residency, he found his life’s work.

“It’s such a magical and incredible thing that you can do this,” says Lopez-Soler, director of the renal transplant program at the Edward Hines Jr. Veterans Affairs Hospital outside Chicago. “You’re watching this organ that was taken out [of the donor], practically lifeless and inert, and through the expertise of surgery it comes to life and becomes pink; it starts to make urine.”

About 100,000 people in the United States are currently waiting for a kidney transplant; on average, they will wait five to seven years. Lopez-Soler is expanding access to this care for veterans.

Kidney transplants are life-changing, he says, not only because kidney disease can make people very sick, but because the main treatment—dialysis, which does some of the kidney’s job outside the body—is so demanding that many patients can’t work or even travel. “Getting a kidney transplant not only fixes the problem, but fixes their lives going forward,” he says. “There is this substantial transformation.”

Growing up in Puerto Rico, Lopez-Soler always expected to become a surgeon (his father is a surgical oncologist). During high school, he discovered the MIT Introduction to Technology, Engineering, and Science (MITES) program, spent a summer on campus, and fell in love with the Institute. “MIT was an incredibly inclusive place,” he says. “Whatever you did, you were welcome. I’ve brought that acceptance with me in my ethos in how I deal with people.”

After majoring in biology at MIT (with a minor in Spanish literature), Lopez-Soler earned his MD and PhD from Northwestern University and completed his surgical residency at Yale New Haven Hospital. Then he practiced in Virginia and New York, where he was director of research at Albany Medical Center.

In 2019, Lopez-Soler was tapped to establish the VA transplant program at Hines, and in its first year, it completed 36 kidney transplants. Last year, the center did 105. He now chairs the Department of Veterans Affairs Transplant Surgery Surgical Advisory Board, which helps develop transplant policies and procedures for the whole VA system.

The grandson of a brigadier general, Lopez-Soler is proud to serve veterans. “I was lucky enough to fall in love with the job because of the people we treat,” he says. “It exposed me to these amazing veterans who have done so much for this country.”

This story also appears in the September/October issue of MIT Alumni News magazine, published by MIT Technology Review.

Photo illustration by Mary Zyskowski; image of Reynold I. Lopez-Soler courtesy of Lopez-Soler.