Author: MIT News

Eleven MIT faculty receive Presidential Early Career Awards

by Jordan Silva | School of Engineering |

Eleven MIT faculty, including nine from the School of Engineering and two from the School of Science, were awarded the Presidential Early Career Award for Scientists and Engineers (PECASE). More than 15 additional MIT alumni were also honored.

Established in 1996 by President Bill Clinton, the PECASE is awarded to scientists and engineers “who show exceptional potential for leadership early in their research careers.” The latest recipients were announced by the White House on Jan. 14 under President Joe Biden. Fourteen government agencies recommended researchers for the award.

The MIT faculty and alumni honorees are among 400 scientists and engineers recognized for innovation and scientific contributions. Those from the School of Engineering and School of Science who were honored are:

  • Tamara Broderick, associate professor in the Department of Electrical Engineering and Computer Science (EECS), was nominated by the Office of Naval Research for her project advancing “Lightweight representations for decentralized learning in data-rich environments.”
  • Michael James Carbin SM ’09, PhD ’15, associate professor in the Department of EECS, was nominated by the National Science Foundation (NSF) for his CAREER award, a project that developed techniques to execute programs reliably on approximate and unreliable computation substrates.
  • Christina Delimitrou, the KDD Career Development Professor in Communications and Technology and associate Professor in the Department of EECS, was nominated by the NSF for her group’s work on redesigning the cloud system stack given new cloud programming frameworks like microservices and serverless compute, as well as designing hardware acceleration techniques that make cloud data centers more predictable and resource-efficient.
  • Netta Engelhardt, the Biedenharn Career Development Associate Professor of Physics, was nominated by the Department of Energy for her research on the black hole information paradox and its implications for the fundamental quantum structure of space and time.
  • Robert Gilliard Jr., the Novartis Associate Professor of Chemistry, was selected based the results generated from his 2020 National Science Foundation CAREER award entitled: “CAREER: Boracycles with Unusual Bonding as Creative Strategies for Main-Group Functional Materials.”
  • Heather Janine Kulik PD ’09, PhD ’09, the Lammot du Pont Professor of Chemical Engineering, was nominated by the NSF for her 2019 proposal entitled “CAREER: Revealing spin-state-dependent reactivity in open-shell single atom catalysts with systematically-improvable computational tools.”
  • Nuno Loureiro, professor in the Department of Nuclear Science and Engineering, was nominated by the NSF for his work on the generation and amplification of magnetic fields in the universe.
  • Robert Macfarlane, associate professor in the Department of Materials Science and Engineering, was nominated by the Department of Defense (DoD)’s Air Force Office of Scientific Research. His research focuses on making new materials using molecular and nanoscale building blocks.
  • Ritu Raman, the Eugene Bell Career Development Professor of Tissue Engineering in the Department of Mechanical Engineering, was nominated by the DoD for her ARO-funded research that explored leveraging biological actuators in next-generation robots that can sense and adapt to their environments.
  • Ellen Roche, the Latham Family Career Development Professor and associate department head in the Department of Mechanical Engineering, was nominated by the NSF for her CAREER award, a project that aims to create a cutting-edge benchtop model combining soft robotics and organic tissue to accurately simulate the motions of the heart and diaphragm.
  • Justin Wilkerson, a visiting associate professor in the Department of Aeronautics and Astronautics, was nominated by the Air Force Office of Scientific Research (AFOSR) for his research primarily related to the design and optimization of novel multifunctional composite materials that can survive extreme environments.

Additional MIT alumni who were honored include: Elaheh Ahmadi ’20, MNG ’21; Ambika Bajpayee MNG ’07, PhD ’15; Katherine Bouman SM ’13, PhD ’17; Walter Cheng-Wan Lee ’95, MNG ’95, PhD ’05; Ismaila Dabo PhD ’08; Ying Diao SM ’10, PhD ’12; Eno Ebong ’99; Soheil Feizi- Khankandi SM ’10, PhD ’16; Mark Finlayson SM ’01, PhD ’12; Chelsea B. Finn ’14; Grace Xiang Gu SM ’14, PhD ’18; David Michael Isaacson PhD ’06, AF ’16; Lewei Lin ’05; Michelle Sander PhD ’12; Kevin Solomon SM ’08, PhD ’12; and Zhiting Tian PhD ’14.

With generative AI, MIT chemists quickly calculate 3D genomic structures

by Anne Trafton | MIT News |

Every cell in your body contains the same genetic sequence, yet each cell expresses only a subset of those genes. These cell-specific gene expression patterns, which ensure that a brain cell is different from a skin cell, are partly determined by the three-dimensional structure of the genetic material, which controls the accessibility of each gene.

MIT chemists have now come up with a new way to determine those 3D genome structures, using generative artificial intelligence. Their technique can predict thousands of structures in just minutes, making it much speedier than existing experimental methods for analyzing the structures.

Using this technique, researchers could more easily study how the 3D organization of the genome affects individual cells’ gene expression patterns and functions.

“Our goal was to try to predict the three-dimensional genome structure from the underlying DNA sequence,” says Bin Zhang, an associate professor of chemistry and the senior author of the study. “Now that we can do that, which puts this technique on par with the cutting-edge experimental techniques, it can really open up a lot of interesting opportunities.”

MIT graduate students Greg Schuette and Zhuohan Lao are the lead authors of the paper, which appears today in Science Advances.

From sequence to structure

Inside the cell nucleus, DNA and proteins form a complex called chromatin, which has several levels of organization, allowing cells to cram 2 meters of DNA into a nucleus that is only one-hundredth of a millimeter in diameter. Long strands of DNA wind around proteins called histones, giving rise to a structure somewhat like beads on a string.

Chemical tags known as epigenetic modifications can be attached to DNA at specific locations, and these tags, which vary by cell type, affect the folding of the chromatin and the accessibility of nearby genes. These differences in chromatin conformation help determine which genes are expressed in different cell types, or at different times within a given cell.

Over the past 20 years, scientists have developed experimental techniques for determining chromatin structures. One widely used technique, known as Hi-C, works by linking together neighboring DNA strands in the cell’s nucleus. Researchers can then determine which segments are located near each other by shredding the DNA into many tiny pieces and sequencing it.

This method can be used on large populations of cells to calculate an average structure for a section of chromatin, or on single cells to determine structures within that specific cell. However, Hi-C and similar techniques are labor-intensive, and it can take about a week to generate data from one cell.

To overcome those limitations, Zhang and his students developed a model that takes advantage of recent advances in generative AI to create a fast, accurate way to predict chromatin structures in single cells. The AI model that they designed can quickly analyze DNA sequences and predict the chromatin structures that those sequences might produce in a cell.

“Deep learning is really good at pattern recognition,” Zhang says. “It allows us to analyze very long DNA segments, thousands of base pairs, and figure out what is the important information encoded in those DNA base pairs.”

ChromoGen, the model that the researchers created, has two components. The first component, a deep learning model taught to “read” the genome, analyzes the information encoded in the underlying DNA sequence and chromatin accessibility data, the latter of which is widely available and cell type-specific.

The second component is a generative AI model that predicts physically accurate chromatin conformations, having been trained on more than 11 million chromatin conformations. These data were generated from experiments using Dip-C (a variant of Hi-C) on 16 cells from a line of human B lymphocytes.

When integrated, the first component informs the generative model how the cell type-specific environment influences the formation of different chromatin structures, and this scheme effectively captures sequence-structure relationships. For each sequence, the researchers use their model to generate many possible structures. That’s because DNA is a very disordered molecule, so a single DNA sequence can give rise to many different possible conformations.

“A major complicating factor of predicting the structure of the genome is that there isn’t a single solution that we’re aiming for. There’s a distribution of structures, no matter what portion of the genome you’re looking at. Predicting that very complicated, high-dimensional statistical distribution is something that is incredibly challenging to do,” Schuette says.

Rapid analysis

Once trained, the model can generate predictions on a much faster timescale than Hi-C or other experimental techniques.

“Whereas you might spend six months running experiments to get a few dozen structures in a given cell type, you can generate a thousand structures in a particular region with our model in 20 minutes on just one GPU,” Schuette says.

After training their model, the researchers used it to generate structure predictions for more than 2,000 DNA sequences, then compared them to the experimentally determined structures for those sequences. They found that the structures generated by the model were the same or very similar to those seen in the experimental data.

“We typically look at hundreds or thousands of conformations for each sequence, and that gives you a reasonable representation of the diversity of the structures that a particular region can have,” Zhang says. “If you repeat your experiment multiple times, in different cells, you will very likely end up with a very different conformation. That’s what our model is trying to predict.”

The researchers also found that the model could make accurate predictions for data from cell types other than the one it was trained on. This suggests that the model could be useful for analyzing how chromatin structures differ between cell types, and how those differences affect their function. The model could also be used to explore different chromatin states that can exist within a single cell, and how those changes affect gene expression.

Another possible application would be to explore how mutations in a particular DNA sequence change the chromatin conformation, which could shed light on how such mutations may cause disease.

“There are a lot of interesting questions that I think we can address with this type of model,” Zhang says.

The researchers have made all of their data and the model available to others who wish to use it.

The research was funded by the National Institutes of Health.

A new vaccine approach could help combat future coronavirus pandemics

by Anne Trafton | MIT News |

A new experimental vaccine developed by researchers at MIT and Caltech could offer protection against emerging variants of SARS-CoV-2, as well as related coronaviruses, known as sarbecoviruses, that could spill over from animals to humans.

In addition to SARS-CoV-2, the virus that causes COVID-19, sarbecoviruses — a subgenus of coronaviruses — include the virus that led to the outbreak of the original SARS in the early 2000s. Sarbecoviruses that currently circulate in bats and other mammals may also hold the potential to spread to humans in the future.

By attaching up to eight different versions of sarbecovirus receptor-binding proteins (RBDs) to nanoparticles, the researchers created a vaccine that generates antibodies that recognize regions of RBDs that tend to remain unchanged across all strains of the viruses. That makes it much more difficult for viruses to evolve to escape vaccine-induced antibodies.

“This work is an example of how bringing together computation and immunological experiments can be fruitful,” says Arup K. Chakraborty, the John M. Deutch Institute Professor at MIT and a member of MIT’s Institute for Medical Engineering and Science and the Ragon Institute of MIT, MGH and Harvard University.

Chakraborty and Pamela Bjorkman, a professor of biology and biological engineering at Caltech, are the senior authors of the study, which appears today in Cell. The paper’s lead authors are Eric Wang PhD ’24, Caltech postdoc Alexander Cohen, and Caltech graduate student Luis Caldera.

Mosaic nanoparticles

The new study builds on a project begun in Bjorkman’s lab, in which she and Cohen created a “mosaic” 60-mer nanoparticle that presents eight different sarbecovirus RBD proteins. The RBD is the part of the viral spike protein that helps the virus get into host cells. It is also the region of the coronavirus spike protein that is usually targeted by antibodies against sarbecoviruses.

RBDs contain some regions that are variable and can easily mutate to escape antibodies. Most of the antibodies generated by mRNA COVID-19 vaccines target those variable regions because they are more easily accessible. That is one reason why mRNA vaccines need to be updated to keep up with the emergence of new strains.

If researchers could create a vaccine that stimulates production of antibodies that target RBD regions that can’t easily change and are shared across viral strains, it could offer broader protection against a variety of sarbecoviruses.

Such a vaccine would have to stimulate B cells that have receptors (which then become antibodies) that target those shared, or “conserved,” regions. When B cells circulating in the body encounter a vaccine or other antigen, their B cell receptors, each of which have two “arms,” are more effectively activated if two copies of the antigen are available for binding to each arm. The conserved regions tend to be less accessible to B cell receptors, so if a nanoparticle vaccine presents just one type of RBD, B cells with receptors that bind to the more accessible variable regions, are most likely to be activated.

To overcome this, the Caltech researchers designed a nanoparticle vaccine that includes 60 copies of RBDs from eight different related sarbecoviruses, which have different variable regions but similar conserved regions. Because eight different RBDs are displayed on each nanoparticle, it’s unlikely that two identical RBDs will end up next to each other. Therefore, when a B cell receptor encounters the nanoparticle immunogen, the B cell is more likely to become activated if its receptor can recognize the conserved regions of the RBD.

“The concept behind the vaccine is that by co-displaying all these different RBDs on the nanoparticle, you are selecting for B cells that recognize the conserved regions that are shared between them,” Cohen says. “As a result, you’re selecting for B cells that are more cross-reactive. Therefore, the antibody response would be more cross-reactive and you could potentially get broader protection.”

In studies conducted in animals, the researchers showed that this vaccine, known as mosaic-8, produced strong antibody responses against diverse strains of SARS-CoV-2 and other sarbecoviruses and protected from challenges by both SARS-CoV-2 and SARS-CoV (original SARS).

Broadly neutralizing antibodies

After these studies were published in 2021 and 2022, the Caltech researchers teamed up with Chakraborty’s lab at MIT to pursue computational strategies that could allow them to identify RBD combinations that would generate even better antibody responses against a wider variety of sarbecoviruses.

Led by Wang, the MIT researchers pursued two different strategies — first, a large-scale computational screen of many possible mutations to the RBD of SARS-CoV-2, and second, an analysis of naturally occurring RBD proteins from zoonotic sarbecoviruses.

For the first approach, the researchers began with the original strain of SARS-CoV-2 and generated sequences of about 800,000 RBD candidates by making substitutions in locations that are known to affect antibody binding to variable portions of the RBD. Then, they screened those candidates for their stability and solubility, to make sure they could withstand attachment to the nanoparticle and injection as a vaccine.

From the remaining candidates, the researchers chose 10 based on how different their variable regions were. They then used these to create mosaic nanoparticles coated with either two or five different RBD proteins (mosaic-2COM and mosaic-5COM).

In their second approach, instead of mutating the RBD sequences, the researchers chose seven naturally occurring RBD proteins, using computational techniques to select RBDs that were different from each other in regions that are variable, but retained their conserved regions. They used these to create another vaccine, mosaic-7COM.

Once the researchers produced the RBD-nanoparticles, they evaluated each one in mice. After each mouse received three doses of one of the vaccines, the researchers analyzed how well the resulting antibodies bound to and neutralized seven variants of SARS-CoV-2 and four other sarbecoviruses.

They also compared the mosaic nanoparticle vaccines to a nanoparticle with only one type of RBD displayed, and to the original mosaic-8 particle from their 2021, 2022, and 2024 studies. They found that mosaic-2COM and mosaic-5COM outperformed both of those vaccines, and mosaic-7COM showed the best responses of all. Mosaic-7COM elicited antibodies with binding to most of the viruses tested, and these antibodies were also able to prevent the viruses from entering cells.

The researchers saw similar results when they tested the new vaccines in mice that were previously vaccinated with a bivalent mRNA COVID-19 vaccine.

“We wanted to simulate the fact that people have already been infected and/or vaccinated against SARS-CoV-2,” Wang says. “In pre-vaccinated mice, mosaic-7COM is consistently giving the highest binding titers for both SARS-CoV-2 variants and other sarbecoviruses.”

Bjorkman’s lab has received funding from the Coalition for Epidemic Preparedness Innovations to do a clinical trial of the mosaic-8 RBD-nanoparticle. They also hope to move mosaic-7COM, which performed better in the current study, into clinical trials. The researchers plan to work on redesigning the vaccines so that they could be delivered as mRNA, which would make them easier to manufacture.

The research was funded by a National Science Foundation Graduate Research Fellowship, the National Institutes of Health, Wellcome Leap, the Bill and Melinda Gates Foundation, the Coalition for Epidemic Preparedness Innovations, and the Caltech Merkin Institute for Translational Research.

Student Program for Innovation in Science and Engineering is a launching pad toward possibility

by Jane Halpern | Department of Electrical Engineering and Computer Science |

When you ask MIT students to tell you the story of how they came to Cambridge, you might hear some common themes: a favorite science teacher; an interest in computers that turned into an obsession; a bedroom decorated with NASA posters and glow-in-the-dark stars.

But for a few, the road to MIT starts with an invitation to a special summer program: not a camp with canoes or cabins or campgrounds, but instead one taking place in classrooms and labs with discussions of Arduinos, variable scope and aliasing, and Michaelis-Menten enzyme kinetics. The classroom and labs are in Barbados at the Cave Hill campus of the University of the West Indies, and all the students are gifted Caribbean high schoolers, ages 16-18, who’ve been selected for the extremely competitive Student Program for Innovation in Science and Engineering (SPISE). Their summer will not include much time for leisure or lots of sleep; instead, they’ll be tackling a five-week high-intensity curriculum with courses in university-level calculus, physics, biochemistry, computer programming, electronics and entrepreneurship, including hands-on projects in the last three. For several students currently on campus, SPISE was their gateway to MIT.

“The full story is even bigger,” says Cardinal Warde, MIT professor of electrical engineering and founder of SPISE, who is originally from Barbados in the Caribbean. “Over the past 10 years, exactly 30 of the 245 students in total from the SPISE program have attended MIT as undergrads and/or graduate students.”

While many SPISE alumni have gone on to Harvard University, Stanford University, Caltech, Princeton University, Columbia University, the University of Pennsylvania, and other prestigious schools, the emphasis on science and technology creates a natural pipeline to MIT, whose faculty and instructors volunteered their time and expertise to help Warde design a curriculum that was both challenging and engaging.

Jacob White, the Cecil H. Green Professor in Electrical Engineering, was one of the first of those volunteers. “When Covid forced SPISE to run remotely, Professor Warde felt it was critical to continue having hands-on engineering labs, and sought my help,” White explains. “Kits were cobbled together using EECS-donated microcontroller boards, motors and magnets; Dinah Sah (the SPISE director) got those kits to students spread over half-a-dozen islands.” White, and several of his graduate students, collaborated to write a curriculum that would give the students enough grounding in fundamentals to empower them to create their own designs.

When SPISE returned to in-person education, Steve Leeb, the Emanuel E. Landsman (1958) Professor in the Department of Electrical Engineering and Computer Science (EECS) and a member of the Research Laboratory of Electronics (RLE), was inspired by the challenge of teaching electronics remotely.

“SPISE is exactly the kind of opportunity we’re looking for in the RLE educational outreach programs: bright, enthusiastic young folks who would benefit from new perspectives on science and engineering — a community of folks where we can bring new perspectives, share energy and excitement, and, ideally, make lifelong connections to our academic programs here at MIT. It’s a natural fit that benefits us all,” says Leeb, who, together with his graduate students, adapted the portable “take-home” Electronics FIRST curriculum pioneered at MIT and taught in course 6.2030. “The Electronics FIRST exercises and lectures are designed to connect electronic circuit techniques — digital gates, microcontrollers, and other electronics technologies — that are recognizable as elements of commercial products,” says Leeb. “So the projects naturally engage students in building with components that have a connection to commercial products and product ideas. This flows naturally into a ‘final project’ that the students create in SPISE, a product of their own conception, for example a music synthesizer.”

Crucially, the curriculum isn’t simplified for the high school students. “We adapted the projects to fit the different program length — SPISE is shorter than a full MIT term,” says Leeb. “We did not reduce the rigor or challenge of the activities, and, in fact, have brought new ideas from the SPISE students back to campus to improve 6.2030.”

Departments beyond EECS pitched in to develop SPISE, with major teaching contributions coming from the Department of Physics, where Lecturer Alex Shvonski, Senior Technical Instructor Caleb Bonyun, and Senior Technical Instructor Joshua Wolfe, who also manages the Physics Instructional Resource Lab, collaborated on developing hands-on projects and on the teaching for both Physics I and Calculus I courses. Additional supplies came from the MIT Sea Grant Program, which supplied underwater robots to SPISE for six consecutive years before the Covid-19 pandemic. (In the wake of the pandemic, the program pivoted to focus on embedded systems.)

But the core inspiration for SPISE doesn’t come from an academic department at all. “SPISE was based on a model that’s proven to work: MITES,” explains Ebony Hearn, executive director of the MIT Introduction to Technology, Engineering, and Science. “The program, which offers access and opportunity to intensive courses in science, technology, engineering, and math for talented high school students in every zip code, has helped thousands of students for nearly 50 years gain admission to top universities and pursue successful careers in STEM while being immersed in a community of caring mentors and leaders in the profession.”

The shared DNA of the two programs is no coincidence. Cardinal Warde has been the faculty director of MITES for the past 27 years, and took the lessons of five decades of the transformative pre-college experience into account when envisioning an equivalent program in the Caribbean. Much like MITES, SPISE encourages its participants to develop a sense of belonging in STEM and to picture the possibilities at top schools; over the years, the program has added sessions with admissions officers from MIT, Columbia, Princeton, and U Penn. “SPISE changed my perspective of myself,” says Chenise Harper, a first-year student at MIT who is currently interested in Course 6-5 (Electrical Engineering With Computing). “It gave me the confidence to apply to universities I thought were completely out of my reach.”

Harper’s trajectory is exactly what the designers of the program hoped for. “We have been very successful with the shorter-term goal of increasing the numbers of Caribbean students pursuing advanced degrees in STEM and grooming the next generation of STEM and business leaders in the Region,” says Dinah Sah ’81, director of the program (and wife of Cardinal Warde). “We have SPISE graduates who have, or are currently pursuing, graduate degrees at the top universities around the world, including (but not limited to) MIT, Stanford, Harvard, Princeton, Dartmouth, Yale, Johns Hopkins, Carnegie Mellon, and Oxford, including a Rhodes Scholar. We fully believe that SPISE graduates represent part of the next generation of STEM and business leaders in the Caribbean and that SPISE has played a significant role in their trajectories.”

Notably, the SPISE program also includes an element of entrepreneurship, encouraging students to envision tech-based solutions to problems in their own backyards. Keonna Simon, who hails from St. Vincent and the Grenadines, developed a business pitch with other SPISE participants for an innovative “reverse vending machine.” “In the Caribbean, tourism is a key contributor to the economy, but littering is an issue that detracts from the beauty of our islands and harms our abundant marine life,” explains Simon, now a junior majoring in Course 6-7 (Computer Science and Molecular Biology). “Our project aimed to tackle this by placing reverse vending machines in heavily polluted areas. People could deposit recyclable plastic bottles, and the machine would convert the weight of the plastic into cash rewards on a card, redeemable for discounts at supermarkets.”

One SPISE alum, Quilee Simeon, decided to work on a renewable energy system at SPISE as a way of addressing global warming’s effects on his homeland of St. Lucia. “I chose to work on the renewable energy project, where we designed and built a prototype wind turbine using low-resource materials like PVC pipes. It was exciting because I thought it had real applications to developing island states like ours, where we don’t have an abundance of the manufacturing materials used in larger countries, and we are disproportionately affected by climate change,” says Simeon. “So building cheap and effective renewable energy resources was, in my view, an important problem to tackle.”

As Simeon worked on his prototype turbine and tackled late nights with his new classmates at SPISE, he realized how different the experience was from his prior schooling. For most students, the summer program is a first time away from home — but for all, it is the first exposure to the firehose-like experience of tackling multiple college-level courses with simultaneous assignments and problem sets. “It was honestly a primer to MIT,” says Simeon. “They not only challenged us with rigorous math and science, but also provided guidance on college applications and explained the vast opportunities a STEM degree could unlock. SPISE changed my view of myself as a scholar, though probably in an unexpected way. I thought I was smart before attending SPISE, but I realized how much I didn’t know and how many things were lacking or wrong with the style of education I had grown used to (rote learning, memorization, etc.). SPISE made me realize that being a scholar isn’t just about consuming knowledge — it’s about creating and applying it.”

The difficulty of the SPISE curriculum is a deliberate choice, made to aid students in preparing for higher education, confirms Sah. “When we started SPISE in 2012, [we decided] to focus on teaching the fundamentals in each of the courses … The homework problems and the quizzes would require the application of these fundamentals to solving challenging problems. This is in distinct contrast to rote memorization of facts, which is the method of learning these students had generally been exposed to. So, yes, this was in fact a very deliberate choice, and a critical change that we wanted to bring to these very high-potential students in their approach to learning and thinking.”

MIT’s emphasis on creative, outside-the-box thinking was just the beginning of the culture shocks that awaited SPISE students who made the transition to an American university from the summer program. Many are surprised by the American students’ habit of referring to their professors by first name, which would be considered disrespectful at home. Conversely, small daily interactions in the Northeast can feel remote and chilly to Caribbean students. “Moving from a small island with just around 100,000 people to Harvard was initially jarring,” says Gerard Porter, who participated in SPISE in 2017 before attending Harvard for his undergraduate degree. “In my first year, I was often met with puzzled stares when I greeted strangers in an elevator or students in my dorm whom I did not know personally. I quickly learned that politeness meant something very different in the Northeastern United States compared to the warm Caribbean.”

Other SPISE alumni report experiencing similar chilliness — literally. Quilee Simeon’s first winter in Cambridge was jarring. “I knew about the concept of winter and was told to expect cold weather, but I never actually knew how cold ‘cold’ was until I felt it myself,” says Simeon. “That was terrible!” Ronaldo Lee, a first-year from Jamaica interested in computer science and electrical engineering, found warmth among fellow SPISE alumni here at MIT. “Nothing beats the tropical climate! But honestly, the community at MIT has been amazing. I was surprised by how quickly I felt comfortable, thanks to the incredible people around me. The Black and Caribbean community especially made me feel at home; I’ve met some truly fascinating, driven, and like-minded people who’ve become close friends. One of the biggest surprises was discovering how similar we all are, despite our different cultural backgrounds. Everyone here is incredibly smart and shares a common drive to make the world a better place and pursue exciting STEM projects.”

The common drive to improve the world through STEM is evident in the paths the SPISE alumni have taken.

Gerard Porter, now a graduate student in the Kiessling Group within the Department of Chemistry at MIT, conducts research “focusing on unraveling the biological roles of glycans that cover all cells on Earth. I work on developing chemical tools to study critical regions of the bacterial cell wall that have been relatively unexplored.” Porter hopes that learning more about the molecular mechanisms at play within cell walls will open the doorway to the development of novel antibiotics.

Quilee Simeon has discovered an affinity for computational neuroscience, and is currently developing a computational model of the C. elegans nervous system. “My hope is that this model organism will prove fruitful for computational neuroscience research as it has for biology,” says Simeon, who plans to work in industry after graduation.

Computational biology has also captured the attention of junior Keonna Simon, who is excited to take courses such as 6.8711 (Computational Systems Biology: Deep Learning in the Life Sciences), saying, “This nexus holds a lot of potential for solving complex biological problems through computational methods, and I’m eager to dive deeper into that space!”

Chenise Harper found SPISE’s emphasis on bringing tech entrepreneurship home inspiring. “Living in the Caribbean has stimulated a dream of a future where robots are partners in rebuilding our community after natural disasters,” she says. “There are also so many issues that I would like to one day contribute to, like climate change issues and even cybersecurity. Electrical Engineering with Computing is the kind of major that will allow me to at least touch on the areas I am interested in, and allow me to explore both software and hardware concepts that excite me and will inspire me to develop a concrete way to give back to the community that has lifted me up to where I am now.”

Ronaldo Lee also found his academic home in computer science and electrical engineering, fabricating and characterizing perovskite solar cells in his Undergraduate Research Opportunities Program project and building a small offshore wind turbine for the Collegiate Wind Competition as part of the MIT WIND team. “I’d love to focus on the energy sector, particularly in improving the grid system and integrating renewable energy sources to ensure more reliable access,” says Lee. “I want to help make energy access more sustainable and inclusive, driving development for the region as a whole.”

Lee’s plans are perfectly in line with the long-term goals set by Warde and Sah as they planned SPISE. “Diversifying the economies of the region and raising the standard of living by stimulating more technology-based entrepreneurship will take time,” says Sah. “We are optimistic that our SPISE graduates will, with time, change the world to make it a better place for all, including the Caribbean.”

Artifacts from a half-century of cancer research

by Becca Hoff | Koch Institute |

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 Nov. 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 zebra fish 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, the Eisen and Chang Career Development Professor and an assistant professor of biology, and Jessica Stark, the 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 Keating’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 is on view in the Koch Institute Public Galleries Monday through Friday, 9 a.m. to 5 p.m., through spring semester 2025.

Troy Van Voorhis to step down as department head of chemistry

by School of Science |

Troy Van Voorhis, the Robert T. Haslam and Bradley Dewey Professor of Chemistry, will step down as department head of the Department of Chemistry at the end of this academic year. Van Voorhis has served as department head since 2019, previously serving the department as associate department head since 2015.

“Troy has been an invaluable partner and sounding board who could always be counted on for a wonderful mix of wisdom and pragmatism,” says Nergis Mavalvala, the Kathleen and Curtis Marble professor of astrophysics and dean of the MIT School of Science. “While department head, Troy provided calm guidance during the Covid pandemic, encouraging and financially supporting additional programs to improve his community’s quality of life.”

“I have had the pleasure of serving as head of our department for the past five-plus years. It has been a period of significant upheaval in our world,” says Van Voorhis. “Throughout it all, one of my consistent joys has been the privilege of working within the chemistry department and across the wider MIT community on research, education, and community building.”

Under Van Voorhis’ leadership, the Department of Chemistry implemented a department-wide statement of values that launched the Diversity, Equity, and Inclusion Committee, a Future Faculty Symposium that showcases rising stars in chemistry, and the Creating Bonds in Chemistry program that partners MIT faculty with chemistry faculty at select historically Black colleges and universities and minority-serving institutions.

Van Voorhis also oversaw a time of tremendous faculty growth in the department with the addition of nine new faculty. During his tenure as head, he also guided the department through a period of significant growth of interest in chemistry with the number of undergraduate majors, enrolled students, graduate students, and graduate student yields all up significantly.

Van Voorhis also had the honor of celebrating with the entire Institute for Professor Moungi Bawendi’s Nobel Prize in Chemistry — the department’s first win in 18 years, since Professor Richard R. Schrock’s win in 2005.

In addition to his service to the department within the School of Science, Van Voorhis had also co-chaired the Working Group on Curricula and Degrees for the MIT Stephen A. Schwarzman College of Computing. This service relates to Van Voorhis’ own research interests and programs.

Van Voorhis’ research lies at the nexus of chemistry and computation, and his work has impact on renewable energy and quantum computing. His lab is focused on developing new methods that provide an accurate description of electron dynamics in molecules and materials. Over the years, his research has led to advances in light-emitting diodes, solar cells, and other devices and technologies crucial to addressing 21st-century energy concerns.

Van Voorhis received his bachelor’s degree in chemistry and mathematics from Rice University and his PhD in chemistry from the University of California at Berkeley in 2001. Following a postdoctoral fellowship at Harvard University, he joined the faculty of MIT in 2003 and was promoted to professor of chemistry in 2012.

He has received many honors and awards, including being named an Alfred P. Sloan research fellow, a fellow of the David and Lucille Packard Foundation, and a recipient of a National Science Foundation CAREER award. He has also received the MIT School of Science’s award for excellence in graduate teaching.

Startup gives surgeons a real-time view of breast cancer during surgery

by Zach Winn | MIT News |

Breast cancer is the second most common type of cancer and cause of cancer death for women in the United States, affecting one in eight women overall.

Most women with breast cancer undergo lumpectomy surgery to remove the tumor and a rimHuman of healthy tissue surrounding the tumor. After the procedure, the removed tissue is sent to a pathologist to look for signs of disease at the edge of the tissue assessed. Unfortunately, about 20 percent of women who have lumpectomies must undergo a second surgery to remove more tissue.

Now, an MIT spinout is giving surgeons a real-time view of cancerous tissue during surgery. Lumicell has developed a handheld device and an optical imaging agent that, when combined, allow surgeons to scan the tissue within the surgical cavity to visualize residual cancer cells.  The surgeons see these images on a monitor that can guide them to remove additional tissue during the procedure.

In a clinical trial of 357 patients, Lumicell’s technology not only reduced the need for second surgeries but also revealed tissue suspected to contain cancer cells that may have otherwise been missed by the standard of care lumpectomy.

The company received U.S. Food and Drug Administration approval for the technology earlier this year, marking a major milestone for Lumicell and the founders, who include MIT professors Linda Griffith and Moungi Bawendi along with PhD candidate W. David Lee ’69, SM ’70. Much of the early work developing and testing the system took place at the Koch Institute for Integrative Cancer Research at MIT, beginning in 2008.

The FDA approval also held deep personal significance for some of Lumicell’s team members, including Griffith, a two-time breast cancer survivor, and Lee, whose wife’s passing from the disease in 2003 changed the course of his life.

An interdisciplinary approach

Lee ran a technology consulting group for 25 years before his wife was diagnosed with breast cancer. Watching her battle the disease inspired him to develop technologies that could help cancer patients.

His neighbor at the time was Tyler Jacks, the founding director of the Koch Institute. Jacks invited Lee to a series of meetings at the Koch involving professors Robert Langer and Bawendi, and Lee eventually joined the Koch Institute as an integrative program officer in 2008, where he began exploring an approach for improving imaging in living organisms with single-cell resolution using charge-coupled device (CCD) cameras.

“CCD pixels at the time were each 2 or 3 microns and spaced 2 or 3 microns,” Lee explains. “So the idea was very simple: to stabilize a camera on a tissue so it would move with the breathing of the animal, so the pixels would essentially line up with the cells without any fancy magnification.”

That work led Lee to begin meeting regularly with a multidisciplinary group including Lumicell co-founders Bawendi, currently the Lester Wolfe Professor of Chemistry at MIT and winner of the 2023 Nobel Prize in Chemistry; Griffith, the School of Engineering Professor of Teaching Innovation in MIT’s Department of Biological Engineering and an extramural faculty member at the Koch Institute; Ralph Weissleder, a professor at Harvard Medical School; and David Kirsch, formerly a postdoc at the Koch Institute and now a scientist at the Princess Margaret Cancer Center.

“On Friday afternoons, we’d get together, and Moungi would teach us some chemistry, Lee would teach us some engineering, and David Kirsch would teach some biology,” Griffith recalls.

Through those meetings, the researchers began to explore the effectiveness of combining Lee’s imaging approach with engineered proteins that would light up where the immune system meets the edge of tumors, for use during surgery. To begin testing the idea, the group received funding from the Koch Institute Frontier Research Program via the Kathy and Curt Marble Cancer Research Fund.

“Without that support, this never would have happened,” Lee says. “When I was learning biology at MIT as an undergrad, genetics weren’t even in the textbooks yet. But the Koch Institute provided education, funding, and most importantly, connections to faculty, who were willing to teach me biology.”

In 2010, Griffith was diagnosed with breast cancer.

“Going through that personal experience, I understood the impact that we could have,” Griffith says. “I had a very unusual situation and a bad kind of tumor. The whole thing was nerve-wracking, but one of the most nerve-wracking times was waiting to find out if my tumor margins were clear after surgery. I experienced that uncertainty and dread as a patient, so I became hugely sensitized to our mission.”

The approach Lumicell’s founders eventually settled on begins two to six hours before surgery, when patients receive the optical imaging agent through an IV. Then, during surgery, surgeons use Lumicell’s handheld imaging device to scan the walls of the breast cavity. Lumicell’s cancer detection software shows spots that highlight regions suspected to contain residual cancer on the computer monitor, which the surgeon can then remove. The process adds less than 7 minutes on average to the procedure.

“The technology we developed allows the surgeon to scan the actual cavity, whereas pathology only looks at the lump removed, and [pathologists] make their assessment based on looking at about 1 or 2 percent of the surface area,” Lee says. “Not only are we detecting cancer that was left behind to potentially eliminate second surgeries, we are also, very importantly, finding cancer in some patients that wouldn’t be found in pathology and may not generate a second surgery.”

Exploring other cancer types

Lumicell is currently exploring if its imaging agent is activated in other tumor types, including prostate, sarcoma, esophageal, gastric, and more.

Lee ran Lumicell between 2008 and 2020. After stepping down as CEO, he decided to return to MIT to get his PhD in neuroscience, a full 50 years since he earned his master’s. Shortly thereafter, Howard Hechler took over as Lumicell’s president and chief operating officer.

Looking back, Griffith credits MIT’s culture of learning for the formation of Lumicell.

“People like David [Lee] and Moungi care about solving problems,” Griffith says. “They’re technically brilliant, but they also love learning from other people, and that’s what makes makes MIT special. People are confident about what they know, but they are also comfortable in that they don’t know everything, which drives great collaboration. We work together so that the whole is bigger than the sum of the parts.”

MIT Schwarzman College of Computing launches postdoctoral program to advance AI across disciplines

by Terri Park | MIT Schwarzman College of Computing |

The MIT Stephen A. Schwarzman College of Computing has announced the launch of a new program to support postdocs conducting research at the intersection of artificial intelligence and particular disciplines.

The Tayebati Postdoctoral Fellowship Program will focus on AI for addressing the most challenging problems in select scientific research areas, and on AI for music composition and performance. The program will welcome an inaugural cohort of up to six postdocs for a one-year term, with the possibility of renewal for a second term.

Supported by a $20 million gift from Parviz Tayebati, an entrepreneur and executive with a broad technical background and experience with startup companies, the program will empower top postdocs by providing an environment that facilitates their academic and professional development and enables them to pursue ambitious discoveries. “I am proud to support a fellowship program that champions interdisciplinary research and fosters collaboration across departments. My hope is that this gift will inspire a new generation of scholars whose research advances knowledge and nurtures innovation that transcends traditional boundaries,” says Tayebati.

“Artificial intelligence holds tremendous potential to accelerate breakthroughs in science and ignite human creativity,” says Dan Huttenlocher, dean of the Schwarzman College of Computing and Henry Ellis Warren Professor of Electrical Engineering and Computer Science. “This new postdoc program is a remarkable opportunity to cultivate exceptional bilingual talent combining AI and another discipline. The program will offer fellows the chance to engage in research at the forefront of both AI and another field, collaborating with leading experts across disciplines. We are deeply thankful to Parviz for his foresight in supporting the development of researchers in this increasingly important area.”

Candidates accepted into the program will work on projects that encompass one of six disciplinary areas: biology/bioengineering, brain and cognitive sciences, chemistry/chemical engineering, materials science and engineering, music, and physics. Each fellow will have a faculty mentor in the disciplinary area as well as in AI.

The Tayebati Postdoctoral Fellowship Program is a key component of a larger focus of the MIT Schwarzman College of Computing aimed at fostering innovative research in computing. As part of this focus, the college has three postdoctoral programs, each of which provides training and mentorship to fellows, broadens their research horizons, and helps them develop expertise in computing, including its intersection with other disciplines.

Other programs include MEnTorEd Opportunities in Research (METEOR), which was established by the Computer Science and Artificial Intelligence Laboratory in 2021. Recently expanded to span MIT through the college, the goal of METEOR is to support exceptional scholars in computer science and AI and to broaden participation in the field.

In addition, the Social and Ethical Responsibilities of Computing (SERC), a cross-cutting initiative of the MIT Schwarzman College of Computing, offers researchers exploring how computing is reshaping society the opportunity to participate as a SERC postdoc. SERC postdocs engage in a number of activities throughout the year, including leading interdisciplinary teams of MIT undergraduate and graduate students, known as SERC Scholars, to work on research projects investigating such topics as generative AI and democracy, combating deepfakes, examining data ownership, and the societal impact of gamification, among others.

Scientists discover molecules that store much of the carbon in space

by Anne Trafton | MIT News Office |

A team led by researchers at MIT has discovered that a distant interstellar cloud contains an abundance of pyrene, a type of large, carbon-containing molecule known as a polycyclic aromatic hydrocarbon (PAH).

The discovery of pyrene in this far-off cloud, which is similar to the collection of dust and gas that eventually became our own solar system, suggests that pyrene may have been the source of much of the carbon in our solar system. That hypothesis is also supported by a recent finding that samples returned from the near-Earth asteroid Ryugu contain large quantities of pyrene.

“One of the big questions in star and planet formation is: How much of the chemical inventory from that early molecular cloud is inherited and forms the base components of the solar system? What we’re looking at is the start and the end, and they’re showing the same thing. That’s pretty strong evidence that this material from the early molecular cloud finds its way into the ice, dust, and rocky bodies that make up our solar system,” says Brett McGuire, an assistant professor of chemistry at MIT.

Due to its symmetry, pyrene itself is invisible to the radio astronomy techniques that have been used to detect about 95 percent of molecules in space. Instead, the researchers detected an isomer of cyanopyrene, a version of pyrene that has reacted with cyanide to break its symmetry. The molecule was detected in a distant cloud known as TMC-1, using the 100-meter Green Bank Telescope (GBT), a radio telescope at the Green Bank Observatory in West Virginia.

McGuire and Ilsa Cooke, an assistant professor of chemistry at the University of British Colombia, are the senior authors of a paper describing the findings, which appears today in Science. Gabi Wenzel, an MIT postdoc in McGuire’s group, is the lead author of the study.

Carbon in space

PAHs, which contain rings of carbon atoms fused together, are believed to store 10 to 25 percent of the carbon that exists in space. More than 40 years ago, scientists using infrared telescopes began detecting features that are thought to belong to vibrational modes of PAHs in space, but this technique couldn’t reveal exactly which types of PAHs were out there.

“Since the PAH hypothesis was developed in the 1980s, many people have accepted that PAHs are in space, and they have been found in meteorites, comets, and asteroid samples, but we can’t really use infrared spectroscopy to unambiguously identify individual PAHs in space,” Wenzel says.

In 2018, a team led by McGuire reported the discovery of benzonitrile — a six-carbon ring attached to a nitrile (carbon-nitrogen) group — in TMC-1. To make this discovery, they used the GBT, which can detect molecules in space by their rotational spectra — distinctive patterns of light that molecules give off as they tumble through space. In 2021, his team detected the first individual PAHs in space: two isomers of cyanonaphthalene, which consists of two rings fused together, with a nitrile group attached to one ring.

On Earth, PAHs commonly occur as byproducts of burning fossil fuels, and they’re also found in char marks on grilled food. Their discovery in TMC-1, which is only about 10 kelvins, suggested that it may also be possible for them to form at very low temperatures.

The fact that PAHs have also been found in meteorites, asteroids, and comets has led many scientists to hypothesize that PAHs are the source of much of the carbon that formed our own solar system. In 2023, researchers in Japan found large quantities of pyrene in samples returned from the asteroid Ryugu during the Hayabusa2 mission, along with smaller PAHs including naphthalene.

That discovery motivated McGuire and his colleagues to look for pyrene in TMC-1. Pyrene, which contains four rings, is larger than any of the other PAHs that have been detected in space. In fact, it’s the third-largest molecule identified in space, and the largest ever detected using radio astronomy.

Before looking for these molecules in space, the researchers first had to synthesize cyanopyrene in the laboratory. The cyano or nitrile group is necessary for the molecule to emit a signal that a radio telescope can detect. The synthesis was performed by MIT postdoc Shuo Zhang in the group of Alison Wendlandt, an MIT associate professor of chemistry.

Then, the researchers analyzed the signals that the molecules emit in the laboratory, which are exactly the same as the signals that they emit in space.

Using the GBT, the researchers found these signatures throughout TMC-1. They also found that cyanopyrene accounts for about 0.1 percent of all the carbon found in the cloud, which sounds small but is significant when one considers the thousands of different types of carbon-containing molecules that exist in space, McGuire says.

“While 0.1 percent doesn’t sound like a large number, most carbon is trapped in carbon monoxide (CO), the second-most abundant molecule in the universe besides molecular hydrogen. If we set CO aside, one in every few hundred or so remaining carbon atoms is in pyrene. Imagine the thousands of different molecules that are out there, nearly all of them with many different carbon atoms in them, and one in a few hundred is in pyrene,” he says. “That is an absolutely massive abundance. An almost unbelievable sink of carbon. It’s an interstellar island of stability.”

Ewine van Dishoeck, a professor of molecular astrophysics at Leiden Observatory in the Netherlands, called the discovery “unexpected and exciting.”

“It builds on their earlier discoveries of smaller aromatic molecules, but to make the jump now to the pyrene family is huge. Not only does it demonstrate that a significant fraction of carbon is locked up in these molecules, but it also points to different formation routes of aromatics than have been considered so far,” says van Dishoeck, who was not involved in the research.

An abundance of pyrene

Interstellar clouds like TMC-1 may eventually give rise to stars, as clumps of dust and gas coalesce into larger bodies and begin to heat up. Planets, asteroids, and comets arise from some of the gas and dust that surround young stars. Scientists can’t look back in time at the interstellar cloud that gave rise to our own solar system, but the discovery of pyrene in TMC-1, along with the presence of large amounts of pyrene in the asteroid Ryugu, suggests that pyrene may have been the source of much of the carbon in our own solar system.

“We now have, I would venture to say, the strongest evidence ever of this direct molecular inheritance from the cold cloud all the way through to the actual rocks in the solar system,” McGuire says.

The researchers now plan to look for even larger PAH molecules in TMC-1. They also hope to investigate the question of whether the pyrene found in TMC-1 was formed within the cold cloud or whether it arrived from elsewhere in the universe, possibly from the high-energy combustion processes that surround dying stars.

The research was funded in part by a Beckman Foundation Young Investigator Award, the Schmidt Family Futures Foundation, the U.S. National Science Foundation, the Natural Sciences and Engineering Research Council of Canada, the Goddard Center for Astrobiology, and the NASA Planetary Science Division Internal Scientist Funding Program.

A new framework to efficiently screen drugs

by Celina Zhao | Institute for Medical Engineering and Science |

Some of the most widely used drugs today, including penicillin, were discovered through a process called phenotypic screening. Using this method, scientists are essentially throwing drugs at a problem — for example, when attempting to stop bacterial growth or fixing a cellular defect — and then observing what happens next, without necessarily first knowing how the drug works. Perhaps surprisingly, historical data show that this approach is better at yielding approved medicines than those investigations that more narrowly focus on specific molecular targets.

But many scientists believe that properly setting up the problem is the true key to success. Certain microbial infections or genetic disorders caused by single mutations are much simpler to prototype than complex diseases like cancer. These require intricate biological models that are far harder to make or acquire. The result is a bottleneck in the number of drugs that can be tested, and thus the usefulness of phenotypic screening.

Now, a team of scientists led by the Shalek Lab at MIT has developed a promising new way to address the difficulty of applying phenotyping screening to scale. Their method allows researchers to simultaneously apply multiple drugs to a biological problem at once, and then computationally work backward to figure out the individual effects of each. For instance, when the team applied this method to models of pancreatic cancer and human immune cells, they were able to uncover surprising new biological insights, while also minimizing cost and sample requirements by several-fold — solving a few problems in scientific research at once.

Zev Gartner, a professor in pharmaceutical chemistry at the University of California at San Francisco, says this new method has great potential. “I think if there is a strong phenotype one is interested in, this will be a very powerful approach,” Gartner says.

The research was published Oct. 8 in Nature Biotechnology. It was led by Ivy Liu, Walaa Kattan, Benjamin Mead, Conner Kummerlowe, and Alex K. Shalek, the director of the Institute for Medical Engineering and Sciences (IMES) and the Health Innovation Hub at MIT, as well as the J. W. Kieckhefer Professor in IMES and the Department of Chemistry. It was supported by the National Institutes of Health and the Bill and Melinda Gates Foundation.

A “crazy” way to increase scale

Technological advances over the past decade have revolutionized our understanding of the inner lives of individual cells, setting the stage for richer phenotypic screens. However, many challenges remain.

For one, biologically representative models like organoids and primary tissues are only available in limited quantities. The most informative tests, like single-cell RNA sequencing, are also expensive, time-consuming, and labor-intensive.

That’s why the team decided to test out the “bold, maybe even crazy idea” to mix everything together, says Liu, a PhD student in the MIT Computational and Systems Biology program. In other words, they chose to combine many perturbations — things like drugs, chemical molecules, or biological compounds made by cells — into one single concoction, and then try to decipher their individual effects afterward.

They began testing their workflow by making different combinations of 316 U.S. Food and Drug Administration-approved drugs. “It’s a high bar: basically, the worst-case scenario,” says Liu. “Since every drug is known to have a strong effect, the signals could have been impossible to disentangle.”

These random combinations ranged from three to 80 drugs per pool, each of which was applied to lab-grown cells. The team then tried to understand the effects of the individual drug using a linear computational model.

It was a success. When compared with traditional tests for each individual drug, the new method yielded comparable results, successfully finding the strongest drugs and their respective effects in each pool, at a fraction of the cost, samples, and effort.

Putting it into practice

To test the method’s applicability to address real-world health challenges, the team then approached two problems that were previously unimaginable with past phenotypic screening techniques.

The first test focused on pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of cancer. In PDAC, many types of signals come from the surrounding cells in the tumor’s environment. These signals can influence how the tumor progresses and responds to treatments. So, the team wanted to identify the most important ones.

Using their new method to pool different signals in parallel, they found several surprise candidates. “We never could have predicted some of our hits,” says Shalek. These included two previously overlooked cytokines that actually could predict survival outcomes of patients with PDAC in public cancer data sets.

The second test looked at the effects of 90 drugs on adjusting the immune system’s function. These drugs were applied to fresh human blood cells, which contain a complex mix of different types of immune cells. Using their new method and single-cell RNA-sequencing, the team could not only test a large library of drugs, but also separate the drugs’ effects out for each type of cell. This enabled the team to understand how each drug might work in a more complex tissue, and then select the best one for the job.

“We might say there’s a defect in a T cell, so we’re going to add this drug, but we never think about, well, what does that drug do to all of the other cells in the tissue?” says Shalek. “We now have a way to gather this information, so that we can begin to pick drugs to maximize on-target effects and minimize side effects.”

Together, these experiments also showed Shalek the need to build better tools and datasets for creating hypotheses about potential treatments. “The complexity and lack of predictability for the responses we saw tells me that we likely are not finding the right, or most effective, drugs in many instances,” says Shalek.

Reducing barriers and improving lives

Although the current compression technique can identify the perturbations with the greatest effects, it’s still unable to perfectly resolve the effects of each one. Therefore, the team recommends that it act as a supplement to support additional screening. “Traditional tests that examine the top hits should follow,” Liu says.

Importantly, however, the new compression framework drastically reduces the number of input samples, costs, and labor required to execute a screen. With fewer barriers in play, it marks an exciting advance for understanding complex responses in different cells and building new models for precision medicine.

Shalek says, “This is really an incredible approach that opens up the kinds of things that we can do to find the right targets, or the right drugs, to use to improve lives for patients.”