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Faculty members were recently granted tenure in the departments of Biology, Brain and Cognitive Sciences, Chemistry, EAPS, and Physics.

School of Science

August 8, 2023

In 2022, nine MIT faculty were granted tenure in the School of Science:

Gloria Choi examines the interaction of the immune system with the brain and the effects of that interaction on neurodevelopment, behavior, and mood. She also studies how social behaviors are regulated according to sensory stimuli, context, internal state, and physiological status, and how these factors modulate neural circuit function via a combinatorial code of classic neuromodulators and immune-derived cytokines. Choi joined the Department of Brain and Cognitive Sciences after a postdoc at Columbia University. She received her bachelor’s degree from the University of California at Berkeley, and her PhD from Caltech. Choi is also an investigator in The Picower Institute for Learning and Memory.

Nikta Fakhri develops experimental tools and conceptual frameworks to uncover laws governing fluctuations, order, and self-organization in active systems. Such frameworks provide powerful insight into dynamics of nonequilibrium living systems across scales, from the emergence of thermodynamic arrow of time to spatiotemporal organization of signaling protein patterns and discovery of odd elasticity. Fakhri joined the Department of Physics in 2015 following a postdoc at University of Göttingen. She completed her undergraduate degree at Sharif University of Technology and her PhD at Rice University.

Geobiologist Greg Fournier uses a combination of molecular phylogeny insights and geologic records to study major events in planetary history, with the hope of furthering our understanding of the co-evolution of life and environment. Recently, his team developed a new technique to analyze multiple gene evolutionary histories and estimated that photosynthesis evolved between 3.4 and 2.9 billion years ago. Fournier joined the Department of Earth, Atmospheric and Planetary Sciences in 2014 after working as a postdoc at the University of Connecticut and as a NASA Postdoctoral Program Fellow in MIT’s Department of Civil and Environmental Engineering. He earned his BA from Dartmouth College in 2001 and his PhD in genetics and genomics from the University of Connecticut in 2009.

Daniel Harlow researches black holes and cosmology, viewed through the lens of quantum gravity and quantum field theory. His work generates new insights into quantum information, quantum field theory, and gravity. Harlow joined the Department of Physics in 2017 following postdocs at Princeton University and Harvard University. He obtained a BA in physics and mathematics from Columbia University in 2006 and a PhD in physics from Stanford University in 2012. He is also a researcher in the Center for Theoretical Physics.

A biophysicist, Gene-Wei Li studies how bacteria optimize the levels of proteins they produce at both mechanistic and systems levels. His lab focuses on design principles of transcription, translation, and RNA maturation. Li joined the Department of Biology in 2015 after completing a postdoc at the University of California at San Francisco. He earned an BS in physics from National Tsinghua University in 2004 and a PhD in physics from Harvard University in 2010.

Michael McDonald focuses on the evolution of galaxies and clusters of galaxies, and the role that environment plays in dictating this evolution. This research involves the discovery and study of the most distant assemblies of galaxies alongside analyses of the complex interplay between gas, galaxies, and black holes in the closest, most massive systems. McDonald joined the Department of Physics and the Kavli Institute for Astrophysics and Space Research in 2015 after three years as a Hubble Fellow, also at MIT. He obtained his BS and MS degrees in physics at Queen’s University, and his PhD in astronomy at the University of Maryland in College Park.

Gabriela Schlau-Cohen combines tools from chemistry, optics, biology, and microscopy to develop new approaches to probe dynamics. Her group focuses on dynamics in membrane proteins, particularly photosynthetic light-harvesting systems that are of interest for sustainable energy applications. Following a postdoc at Stanford University, Schlau-Cohen joined the Department of Chemistry faculty in 2015. She earned a bachelor’s degree in chemical physics from Brown University in 2003 followed by a PhD in chemistry at the University of California at Berkeley.

Phiala Shanahan’s research interests are focused around theoretical nuclear and particle physics. In particular, she works to understand the structure and interactions of hadrons and nuclei from the fundamental degrees of freedom encoded in the Standard Model of particle physics. After a postdoc at MIT and a joint position as an assistant professor at the College of William and Mary and senior staff scientist at the Thomas Jefferson National Accelerator Facility, Shanahan returned to the Department of Physics as faculty in 2018. She obtained her BS from the University of Adelaide in 2012 and her PhD, also from the University of Adelaide, in 2015.

Omer Yilmaz explores the impact of dietary interventions on stem cells, the immune system, and cancer within the intestine. By better understanding how intestinal stem cells adapt to diverse diets, his group hopes to identify and develop new strategies that prevent and reduce the growth of cancers involving the intestinal tract. Yilmaz joined the Department of Biology in 2014 and is now also a member of Koch Institute for Integrative Cancer Research. After receiving his BS from the University of Michigan in 1999 and his PhD and MD from University of Michigan Medical School in 2008, he was a resident in anatomic pathology at Massachusetts General Hospital and Harvard Medical School until 2013.

In 2023, five MIT faculty were granted tenure in the School of Science:

Physicist Riccardo Comin explores the novel phases of matter that can be found in electronic solids with strong interactions, also known as quantum materials. His group employs a combination of synthesis, scattering, and spectroscopy to obtain a comprehensive picture of these emergent phenomena, including superconductivity, (anti)ferromagnetism, spin-density-waves, charge order, ferroelectricity, and orbital order. Comin joined the Department of Physics in 2016 after postdoctoral work at the University of Toronto. He completed his undergraduate studies at the Universita’ degli Studi di Trieste in Italy, where he also obtained a MS in physics in 2009. Later, he pursued doctoral studies at the University of British Columbia, Canada, earning a PhD in 2013.

Netta Engelhardt researches the dynamics of black holes in quantum gravity and uses holography to study the interplay between gravity and quantum information. Her primary focus is on the black hole information paradox, that black holes seem to be destroying information that, according to quantum physics, cannot be destroyed. Engelhardt was a postdoc at Princeton University and a member of the Princeton Gravity Initiative prior to joining the Department of Physics in 2019. She received her BS in physics and mathematics from Brandeis University and her PhD in physics from the University of California at Santa Barbara. Engelhardt is a researcher in the Center for Theoretical Physics and the Black Hole Initiative at Harvard University.

Mark Harnett studies how the biophysical features of individual neurons endow neural circuits with the ability to process information and perform the complex computations that underlie behavior. As part of this work, his lab was the first to describe the physiological properties of human dendrites. He joined the Department of Brain and Cognitive Sciences and the McGovern Institute for Brain Research in 2015. Prior, he was a postdoc at the Howard Hughes Medical Institute’s Janelia Research Campus. He received his BA in biology from Reed College in Portland, Oregon and his PhD in neuroscience from the University of Texas at Austin.

Or Hen investigates quantum chromodynamic effects in the nuclear medium and the interplay between partonic and nucleonic degrees of freedom in nuclei. Specifically, Hen utilizes high-energy scattering of electron, neutrino, photon, proton and ion off atomic nuclei to study short-range correlations: temporal fluctuations of high-density, high-momentum, nucleon clusters in nuclei with important implications for nuclear, particle, atomic, and astrophysics. Hen was an MIT Pappalardo Fellow in the Department of Physics from 2015 to 2017 before joining the faculty in 2017. He received his undergraduate degree in physics and computer engineering from the Hebrew University and earned his PhD in experimental physics at Tel Aviv University.

Sebastian Lourido is interested in learning about the vulnerabilities of parasites in order to develop treatments for infectious diseases and expand our understanding of eukaryotic diversity. His lab studies many important human pathogens, including Toxoplasma gondii, to model features conserved throughout the phylum. Lourido was a Whitehead Fellow at the Whitehead Institute for Biomedical Research until 2017, when he joined the Department of Biology and became a Whitehead Member. He earned his BS from Tulane University in 2004 and his PhD from Washington University in St. Louis in 2012.

Faculty and staff recall Goldman’s unending commitment to his work for more than three decades.

Lillian Eden | Department of Biology

August 7, 2023

Last fall, Stephen “Steve” Goldman passed away at 59 after a courageous battle with amyotrophic lateral sclerosis (ALS). Prior to his passing, Goldman had worked at MIT for more than 30 years, first with Information Systems and Technology, then for the Computational and Systems Biology Initiative, and then in the Department of Biology.

“Steve was an institution,” says Stuart Levine, director of the BioMicro Center in the biology department and Goldman’s supervisor for more than a decade. According to Levine, Goldman was the type of person who had his “whole being” wrapped up in the job: “He did a little bit of everything, and that’s really hard to find these days.”

Steve Goldman was one of the first hires for the fledgling BioMicro Center, according to former supervisor Peter Sorger, whose is now the Otto Krayer Professor of Systems Pharmacology in the Department of Systems Biology at Harvard Medical School. Goldman, Sorger says, was essential for setting up the Department of Biology’s first server-based computing system.

“He brought great enthusiasm and skill to the role, and I also appreciated his sangfroid and sense of humor. This was essential because we were inventing the center’s infrastructure and mission on the fly and were often in the dark — and also down in the steam tunnels. Steve was a real pioneer,” Sorger says.

Before coming to MIT, Goldman lived in New York and worked on Wall Street. He met his wife of 32 years, Brenda Goldman (née Mahar), on a boat in the middle of the Caribbean Sea.

“He came up to me in a white tuxedo and asked me to have dinner,” Brenda Goldman recalls.

They clicked immediately. Around the time of their wedding two years later, Brenda had found a job in Cambridge, Massachusetts, and they were both eager for Steve to find work in the area, far from the high-stress environment of Wall Street.

“I found an ad at MIT and I said, ‘This sounds very much like you,’” Brenda says. After several interviews, he found out he’d gotten a job at MIT the day before their wedding — and the rest, as they say, is history.

Whether it was a weekend or a holiday, if Goldman got an alert that something was wrong, he would always try to follow up, fix the problem, or go in to offer hands-on help, according to Levine.

Brenda even accompanied him a few times, noticing that “there was always somebody around who waved or said hello. We couldn’t get out of the building without seeing someone, no matter which building it was,” she says.

Former department head Alan Grossman recalls many casual conversations about sports, especially baseball and softball.

“He always greeted me with a warm smile and ‘Hello, professor,’” Grossman says. “He truly loved working in our department, and we miss him.”

Goldman’s second love, according to Brenda Goldman, was refereeing sports. Steve would often get to work early so he could wrap up in time to referee or umpire games.

“He had something for almost every season of the year except winter,” Brenda says. “He liked it for the exercise, but he also liked it because it got him off his office chair and interacting with people.”

Steve Goldman was organized — but his workspace was notably less so. It was notorious for being filled with stuff — piles of memory sticks, CDs, cables, and devices open and in various stages of repair. However, Brenda says, “If you told him something broke, he knew what pile of things to pull the magic out of to make it work.”

Levine says Goldman’s death came as a bit of a shock: He had been answering emails just days before his passing.

“He always, always loved working for MIT,” Brenda Goldman says. “He loved computers, and the work gave his life purpose.”

Following his death, the Department of Biology made a contribution in Goldman’s memory to the ALS Association of Massachusetts. In addition to Brenda, his wife of 32 years, Goldman is survived by his children Kevin and Jason Goldman, in-laws, and many nieces and nephews.

August 2, 2023

Greta Friar | Whitehead Institute

August 4, 2023

MIT PhD student Kathrin Kajderowicz is studying how hibernation-like states could pave the way for new hypothermic therapies.

Department of Brain and Cognitive Sciences

August 4, 2023

In 2020, Kathrin “Kat” Kajderowicz’s father passed away from lung cancer. Kajderowicz was in charge of her father’s health care for as long as she can remember. While he suffered from various cardiovascular issues for several years, it wasn’t until the beginning of the Covid-19 pandemic that he was diagnosed with late-stage metastatic small-cell lung cancer. Jumping into a primary caregiver position, she closely monitored the treatments he received from doctors to no avail. “I was frustrated with the many medications he was prescribed without the doctors fully understanding how they interacted with each other,” she says. Even if a single physician had been overseeing his comprehensive treatment plan, she says, they still could not definitively say whether the medication combinations have adverse effects that outweigh any positive impact.

This frustration set her on a scientific journey that has now culminated in her research as a PhD student at MIT’s Department of Brain and Cognitive Sciences (BCS) and the Whitehead Institute for Biomedical Research. “My experience led me to a significant medical problem: How can we eventually shift the medical paradigm to develop treatments that consider not only one specific pathway or problem but contextualize systemic tissue or organ dysfunction?”

To engage with this problem, Kajderowicz studies animals uniquely adapted to handle different stressors and environments, possibly modeling human disease states. “Perhaps we can turn to nature and see how different organisms have adapted to overcome and mitigate similar challenges,” she says.

Kajderowicz now works in Professor Siniša Hrvatin’s lab at Whitehead, where she researches cold tolerance. “I’m interested in exploring the mechanisms underlying cellular cold tolerance in hibernating organisms.” Engineering cold tolerance and stasis has many potential revolutionary future applications. In the near term, her work could improve organ transplantation and cell or tissue preservation. In the longer term, she hopes her work could catalyze a shift in the medical field away from its current crisis-mode approach: “By slowing down bodily processes and disease progression, a lower metabolic state could pave the way for a new class of hypothermic therapies that induce human hibernation-like states for cells, organs, or even whole organisms.”

First-generation student and scientist

Kajderowicz’s clearheaded pursuit of fundamental, large-scale scientific questions has propelled her impressive career as a young scientist. Recently, she was awarded the Paul and Daisy Soros Fellowship for New Americans, recognizing her unique path as the daughter of immigrants from Soviet Poland. Her parents arrived in the United States without having completed higher education degrees, without any savings, knowledge of English, medical insurance, or immigration papers. They worked hard to make a living — her father was a construction worker and her mother a housekeeper — using much of their earnings to become naturalized citizens.

Kajderowicz developed an early interest in a scientific career. “My parents, who didn’t go to college, didn’t push me toward any specific profession,” she says. “This gave me the freedom to explore any field I wanted, and my curiosity naturally led me to science.”

As a teenager, she worked as a golf caddie to help her parents financially. Clients at the golf course assisted her in obtaining internships at biotech and tech companies. Having won Best in Category at the Illinois State Science Fair, Kajderowicz received a substantial scholarship to support her studies at Cornell University, but she continued working to pay for her expenses and tuition. At Cornell, Kajderowicz joined the renowned Lab of Ornithology, where she applied machine-learning techniques to study songbird communication and other behavioral patterns.

Kajderowicz’s journey as a neuroscientist began at Harvard Medical School in Professor Connie Cepko’s lab, where she studied the developmental trajectory of a population of retinal interneurons. “Learning how to identify cell signatures was a fascinating introduction to the complexity of life. But I ultimately realized I wanted to pursue the questions that kept me up at night — both how we process information and how and why these processes change during aging. For me, these are life’s biggest unanswered questions, and I believe neuroscience is the foundation for everything. This led me to MIT’s Department of Brain and Cognitive Sciences.”

Learning from hamsters

Kajderowicz applied and was admitted to over two dozen graduate programs — “but I knew I wanted to go to MIT BCS. That was a no-brainer,” she says. “The department has faculty members in all levels of neuroscience: the cellular and molecular, systems, computational, and cognitive levels. It’s amazing to have all these people under one roof.”

Shortly after starting her graduate work at MIT, Kajderowicz realized she wanted to focus on the cellular level. “I think it’s important first to understand how things work within cells before focusing on function and systems.” She also seeks a translational avenue connecting theory and therapy, bridging the gap between basic science and applied treatment.

Kajderowicz found what she sought at the Whitehead Institute’s Hrvatin Lab and Weissman Lab. “It’s truly unique to have access to two very different communities at MIT. In BCS, I am seen as a biologist, while at the Whitehead Institute, I am more of a neuroscientist. It’s great having folks from different training backgrounds challenging my ideas and work.”

Instead of working directly on how cognition is encoded at the cellular level, Kajderowicz decided to embark on a project that would allow her to figure out how different species survive extreme stressors and environments. She is now developing tools to study cold tolerance across several species on the cellular level.

“Hibernating hamsters can safely endure prolonged durations during which their body temperature drops to 4 degrees [Celsius]. By taking a comparative species approach, I want to identify whether hibernators are uniquely genetically programmed to withstand these conditions or whether non-hibernators don’t activate these genetic pathways,” she says. Next, Kajderowicz hopes to figure out how to transfer or activate cold-protective effects to human cells and, someday, whole humans. While she isn’t directly studying the root of cognition, she hopes her research will help maintain or enhance cognitive functioning throughout aging by pushing the boundaries of the types of medicines and therapeutics available.

Building a scientific community

Kajderowicz’s involvement in the scientific community extends beyond her immediate work. At the height of the pandemic, she initiated a digital platform facilitating conversations on biotechnology trends among researchers, biotech professionals, venture capitalists, and others interested in staying updated on cutting-edge developments. Known as “DNA Deviants,” the community she built consists of several thousand active members on several social media platforms.

“It started with an informal journal club I had with some friends, where we would meet over coffee and discuss new papers. Then, when the pandemic shut down everything, I started a real-time podcast on the Clubhouse app with a friend, discussing emerging biotech trends. Eventually, it became an online journal club, and people just kept joining. We got experts to serendipitously join conversations within their realm of expertise from around the world.” Today, almost a dozen PhD, MD-PhD, and motivated undergraduates worldwide take turns leading conversations with different paper authors.

“It’s been incredibly rewarding to remain connected not only to my work, but also to gain a comprehensive understanding of what’s happening in the world,” Kajderowicz says. “You always need to look beyond your immediate circle.”

Merrill Meadow | Whitehead Institute

July 31, 2023

MIT researchers find timing and dosage of DNA-damaging drugs are key to whether a cancer cell dies or enters senescence.

Bendta Schroeder | Koch Institute

July 31, 2023

Despite the proliferation of novel therapies such as immunotherapy or targeted therapies, radiation and chemotherapy remain the frontline treatment for cancer patients. About half of all patients still receive radiation and 60-80 percent receive chemotherapy.

Both radiation and chemotherapy work by damaging DNA, taking advantage of a vulnerability specific to cancer cells. Healthy cells are more likely to survive radiation and chemotherapy since their mechanisms for identifying and repairing DNA damage are intact. In cancer cells, these repair mechanisms are compromised by mutations. When cancer cells cannot adequately respond to the DNA damage caused by radiation and chemotherapy, ideally, they undergo apoptosis or die by other means.

However, there is another fate for cells after DNA damage: senescence — a state where cells survive, but stop dividing. Senescent cells’ DNA has not been damaged enough to induce apoptosis but is too damaged to support cell division. While senescent cancer cells themselves are unable to proliferate and spread, they are bad actors in the fight against cancer because they seem to enable other cancer cells to develop more aggressively. Although a cancer cell’s fate is not apparent until a few days after treatment, the decision to survive, die, or enter senescence is made much earlier. But, precisely when and how that decision is made has not been well understood.

In an open-access study of ovarian and osteosarcoma cancer cells appearing July 19 in Cell Systems, MIT researchers show that cell signaling proteins commonly associated with cell proliferation and apoptosis instead commit cancer cells to senescence within 12 hours of treatment with low doses of certain kinds of chemotherapy.

“When it comes to treating cancer, this study underscores that it’s important not to think too linearly about cell signaling,” says Michael Yaffe, who is a David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study. “If you assume that a particular treatment will always affect cancer cell signaling in the same way — you may be setting yourself up for many surprises, and treating cancers with the wrong combination of drugs.”

Using a combination of experiments with cancer cells and computational modeling, the team investigated the cell signaling mechanisms that prompt cancer cells to enter senescence after treatment with a commonly used anti-cancer agent. Their efforts singled out two protein kinases and a component of the AP-1 transcription factor complex as highly associated with the induction of senescence after DNA damage, despite the well-established roles for all of these molecules in promoting cell proliferation in cancer.

The researchers treated cancer cells with low and high doses of doxorubicin, a chemotherapy that interferes with the function with topoisomerase II, an enzyme that breaks and then repairs DNA strands during replication to fix tangles and other topological problems.

By measuring the effects of DNA damage on single cells at several time points ranging from six hours to four days after the initial exposure, the team created two datasets. In one dataset, the researchers tracked cell fate over time. For the second set, researchers measured relative cell signaling activity levels across a variety of proteins associated with responses to DNA damage or cellular stress, determination of cell fate, and progress through cell growth and division.

The two datasets were used to build a computational model that identifies correlations between time, dosage, signal, and cell fate. The model identified the activities of the MAP kinases Erk and JNK, and the transcription factor c-Jun as key components of the AP-1 protein likewise understood to involved in the induction of senescence. The researchers then validated these computational findings by showing that inhibition of JNK and Erk after DNA damage successfully prevented cells from entering senescence.

The researchers leveraged JNK and Erk inhibition to pinpoint exactly when cells made the decision to enter senescence. Surprisingly, they found that the decision to enter senescence was made within 12 hours of DNA damage, even though it took days to actually see the senescent cells accumulate. The team also found that with the passage of more time, these MAP kinases took on a different function: promoting the secretion of proinflammatory proteins called cytokines that are responsible for making other cancer cells proliferate and develop resistance to chemotherapy.

“Proteins like cytokines encourage ‘bad behavior’ in neighboring tumor cells that lead to more aggressive cancer progression,” says Tatiana Netterfield, a graduate student in the Yaffe lab and the lead author of the study. “Because of this, it is thought that senescent cells that stay near the tumor for long periods of time are detrimental to treating cancer.”

This study’s findings apply to cancer cells treated with a commonly used type of chemotherapy that stalls DNA replication after repair. But more broadly, the study emphasizes that “when treating cancer, it’s extremely important to understand the molecular characteristics of cancer cells and the contextual factors such as time and dosing that determine cell fate,” explains Netterfield.

The study, however, has more immediate implications for treatments that are already in use. One class of Erk inhibitors, MEK inhibitors, are used in the clinic with the expectation that they will curb cancer growth.

“We must be cautious about administering MEK inhibitors together with chemotherapies,” says Yaffe. “The combination may have the unintended effect of driving cells into proliferation, rather than senescence.”

In future work, the team will perform studies to understand how and why individual cells choose to proliferate instead of enter senescence. Additionally, the team is employing next-generation sequencing to understand which genes c-Jun is regulating in order to push cells toward senescence.

This study was funded, in part, by the Charles and Marjorie Holloway Foundation and the MIT Center for Precision Cancer Medicine.

A new approach opens the door to a greater understanding of protein-microbe interactions.

Lillian Eden | Department of Biology

July 19, 2023

Your mouth is a crucial interface between the outside world and the inside of your body. Everything you breathe, chew, or drink interacts with your oral cavity — the proteins and the microbes, including microbes that can harm us. When things go awry, the result can range from the mild, like bad breath, to the serious, like tooth and gum decay, to more dire effects in the gut and other parts of the body.

Even though the oral microbiome plays a critical role as a front-line defense for human health and disease, we still know very little about the intricacies of host-microbe interactions in the complex physiological environment of the mouth; a better understanding of those interactions is key to developing treatments for human disease.

In a recent study published in PNAS, a team of scientists from MIT and elsewhere revealed that one of the most abundant proteins found in our saliva binds to the surface of select microbes found in the mouth. The findings shed light on how salivary proteins and mucus play a role in maintaining the oral cavity microbiome.

The collaboration involved members of the labs of Barbara Imperiali in the MIT Department of Biology and Laura Kiessling in the MIT Department of Chemistry, as well as the groups of Stefan Ruhl at the University at Buffalo School of Dental Medicine and Catherine Grimes at the University of Delaware.

The work is focused on an abundant oral cavity protein called zymogen granule protein 16 homolog B (ZG16B). Finding ZG16B’s interaction partners and gaining insight into its function were the overarching goals of the project. To accomplish this, Soumi Ghosh, a postdoc in the Imperiali lab, and colleagues engineered ZG16B to add reporter tags such as fluorophores. They called these modified proteins “microbial glycan analysis probes (mGAPs)” because they allowed them to identify ZG16B binding partners using complementary methods. They applied the probes to samples of healthy oral microbiomes to identify target microbes and binding partners.

The results excited them.

“ZG16B didn’t just bind to random bacteria. It was very focused on certain species, including a commensal bacteria called Streptococcus vestibularis,” says Ghosh, who is first author on the paper.

Commensal bacteria are found in a normal healthy microbiome and do not cause disease.

Using the mGAPs, the team showed that ZG16B binds to cell wall polysaccharides of the bacteria, which indicates that ZG16B is a lectin, a carbohydrate-binding protein. In general, lectins are responsible for cell-cell interactions, signaling pathways, and some innate immune responses against pathogens. “This is the first time that it has been proven experimentally that ZG16B acts as a lectin because it binds to the carbohydrates on the cell surface or cell wall of the bacteria,” Ghosh highlights.

ZG16B was also shown to recruit Mucin 7 (MUC7), a salivary glycoprotein in the oral cavity, and together the results suggest that ZG16B may help maintain a healthy balance in the oral microbiome by forming a complex with MUC7 and certain bacteria. The results indicate that ZG16B regulates the bacteria’s abundance by preventing overgrowth through agglutination when the bacteria exceed a certain level of growth.

“ZG16B, therefore, seems to function as a missing link in the system; it binds to different types of glycans — the microbial glycans and the mucin glycans — and ultimately, maintains a healthy balance in our oral cavity,” Ghosh says.

Further work with this probe and samples of oral microbiome from healthy and diseased subjects could also reveal the lectin’s importance for oral health and disease.

Current attention is focused on developing and applying additional mGAPs based on other human lectins, such as those found in serum, liver, and intestine to reveal their binding specificities and their roles in host-microbe interactions.

“The research carried out in this collaboration exemplifies the kind of synergy that made me excited to move to MIT five years ago,” says Kiessling. “I’ve been able to work with outstanding scientists who share my interest in the chemistry and the biology of carbohydrates.”

Kiessling and Imperiali, both senior authors of the paper, came up with the term for the probes they’re creating: “mGAPS to fill in the gaps” in our understanding of the role of lectins in the human microbiome, according to Ghosh.

“If we want to develop therapeutics against bacterial infection, we need a better understanding of host-microbe interactions,” Ghosh says. “The significance of our study is to prove that we can make very good probes for microbial glycans, find out their importance in the front-line defense of the immune system, and, ultimately, come up with a therapeutic approach to disease.”

This research was supported by the National Institute of Health.

Greta Friar | Whitehead Institute

July 7, 2023