Jennifer Yang, '97, has been drawing on her biology degree for making spirits at a craft distillery in Maryland.
Jessica R. Simpson | Slice of MIT
October 15, 2024
If you had told Jennifer Yang ’97 during her time as a Course 7 major at MIT that she would use her biology degree to run a distillery, she wouldn’t have believed you.
“When I was at MIT, I looked at entrepreneurs and I thought, ‘Oh my gosh, that’s not me. I’m not one of those people who are so innovative and gutsy and brave,’” Yang says.
Managing a distillery is a passion that matured in Yang over time—much like the complex flavor of a barrel-aged whiskey. After graduating from MIT, the New York-native moved to Washington, DC, to pursue a career in management and technology consulting, which involved a lot of after-hours networking events. While building connections with colleagues over a glass of whiskey—a drink that was particularly popular with clients—Yang discovered her passion. Over the course of 10 years, she researched the science of making spirits, explored different small distilleries, and even started a whiskey tasting club.
“Being a science geek at heart and being very curious, I went down this rabbit hole pretty quickly in terms of wanting to learn more about it,” Yang explains.
In November 2022, she and her husband opened Covalent Spirits, a craft distillery, tasting room, and event space in Westminster, Maryland. In addition to producing bourbon whiskey, Covalent Spirits distills and blends vodka, gin, rum, and liqueurs. One of the bar’s unique and in-demand offerings is the “pH,” or “power of hydrogen,” cocktail, which uses the acidity of lemonade to turn a blue tea into a vibrant purple. Yang still works in consulting, but you can find her in her element behind the bar, engineering “pH” (and many other) cocktails Thursday through Saturday.
In fact, the shared MIT connection between alumni inspired Yang to name her company Covalent Spirits. One year, at an MIT gathering, Yang started talking to another alum about planning events for undergrad classes that shared years at MIT—what they called “covalent classes.” Yang has since incorporated literal and metaphorical covalent bonds (a chemical connection between atoms formed by sharing) into every facet of her business: from the chemistry of making spirits, to the design of the distillery logo, to the company’s emphasis on community.
“While we are striving to create really good products, we also want to create a space and experiences for people to get together and geek out over a common interest, to celebrate an occasion, or to connect over anything,” Yang elaborates. “You share a drink, you share an experience, you share a community. Bonding through sharing is the covalent spirit.”
Structural intuitions lead to structural insights
Jennifer Viegas | PNAS
November 8, 2024
HHMI Investigator and Professor of Biology and Chemistry Catherine Drennan has spent a distinguished career addressing challenging and wide-ranging structural biology problems.
Catherine Drennan, a Howard Hughes Medical Institute investigator and professor and a professor of biology and chemistry at the Massachusetts Institute of Technology (MIT), has spent a distinguished career addressing challenging and wide-ranging structural biology problems. These include her discovery, while she was a graduate student, of the structure of vitamin B12 bound to protein and her recent determination at atomic resolution of the structure of an active ribonucleotide reductase (RNR) with water molecules, findings reported in her Inaugural Article (IA) (1).
Drennan, who was elected to the National Academy of Sciences in 2023, has uncovered the form and function of metalloenzymes that use metal cofactors to catalyze chemical reactions involving free radicals. Metalloenzymes are of broad human health and environmental interest; some are promising antibiotic and cancer drug targets, whereas others hold the potential for bioremediation efforts, such as converting carbon dioxide into biofuels.
Family of Accomplished Scientists
Drennan was raised in New York City by her father, an obstetrician–gynecologist, and her mother, an anthropologist. Her father was born in Germany and attended medical school at the University of Hamburg. Harboring antifascist leanings, he fled Germany in 1933. He completed medical training in Geneva, Switzerland, before obtaining political asylum in 1940 in the United States, where he became one of the first doctors to practice the Lamaze Method of natural childbirth.
Drennan’s mother attended Antioch College, where she was a student of civil engineer Arthur Ernest Morgan, who was appointed in 1948 to India’s first University Education Commission. She accompanied Morgan to India and served as his administrative assistant before earning her doctorate in anthropology at Cornell University.
“Both my parents were endlessly curious,” says Drennan. “My father was fascinated by the molecular basis of medicine, and my mother was fascinated by people and instilled in me her love for storytelling, teaching, and mentoring.”
Diagnosed with Dyslexia
Although she was an attentive student, Drennan did not learn to read until her second time through sixth grade. “When I finally learned how to read, it was by memorizing the shapes of words,” says Drennan, who was diagnosed with dyslexia when she was in first grade. “Over time I became very good at shape recognition. I am not disabled; I am differently abled. The skill set that I developed to compensate for my dyslexia has made me a world-class structural biologist. We all have strengths and weaknesses, and my ‘weakness’ is also my superpower.”
She was accepted to Vassar College, where she earned a bachelor’s degree in chemistry in 1985. “Miriam Rossi was my undergraduate chemistry research advisor, and she believed in me before I believed in me,” Drennan says. Upon Rossi’s advice, Drennan pursued a doctorate, but not before teaching high-school science and drama at Scattergood Friends School in Iowa.
Following three years of high-school teaching, Drennan pursued graduate studies at the University of Michigan, Ann Arbor, where she earned a PhD in 1995, served as a research fellow from 1995 to 1996, and was mentored by biochemists Martha Ludwig and Rowena Matthews. “They treated me as a colleague, allowing me to see myself as a scientist of value,” Drennan says. “I learned so much from these two incredible scientists. They are, and always will be, my heroes.”
Structure of Vitamin B12 Bound to Protein
With Ludwig et al., Drennan determined the structure of cobalamin (vitamin B12) bound to protein (2). This crystal structure revealed how the protein modulates the reactivity of the B12 cofactor to enable its critical roles in metabolism.
From 1996 to 1999, Drennan did a postdoctoral stint at the California Institute of Technology, under the mentorship of structural biologist Douglas Rees. “Doug taught by example that one does not have to be cutthroat to succeed in the competitive area of structural biology,” she says. “He has continued to mentor me throughout my career, helping me through challenging times.”
Another important mentor was chemist JoAnne Stubbe, a leader in the study of RNRs who recruited Drennan to MIT in 1999 as an assistant professor of chemistry and has been her collaborator for the past 25 years. Drennan says, “Her passion for scientific discovery is unmatched and has inspired me to keep digging to try to understand, at the most fundamental level, how ribonucleotide reductase works.” Drennan advanced to an associate professorship at MIT in 2004 and a full professorship in 2006.
Revealing Metalloenzyme Form and Function
Drennan’s group continues to study B12 and has provided numerous snapshots of cobalamin-dependent proteins and protein complexes. The findings have changed what is known about B12 functions and mechanisms. Using X-ray crystallography, the researchers unveiled a protein complex capable of methyl transfer from folate to B12 (3). They obtained snapshots of the biological process involved in loading B12 into an enzyme (4) and provided structural data on how B12 can be repurposed from enzyme cofactor to light sensor (5).
Drennan has also worked on uncovering the structures of enzymes containing radical S-adenosylmethionine (SAM) cofactors. Drennan and colleagues revealed an X-ray structure of a radical SAM enzyme (6), helping to establish the “core” fold for an enzyme superfamily that has over 100,000 members. Her group further elucidated structures of SAM family members with functions including posttranslational modification (7), antibiotic and antiviral compound biosynthesis (8, 9), and vitamin biosynthesis (6, 10).
Mononuclear nonheme iron enzymes are also of interest to Drennan. The cofactor is simple, but the reactions catalyzed are complex. Her group reported the structure of a nonheme iron halogenase, showing that the halogen binds directly to the catalytic iron (11). Drennan says, “This was a complete surprise that required new mechanistic proposals to be written.”
“Oceanic Methane Paradox”
Early in her independent career, Drennan determined one of the first structures of a nickel-iron-sulfur-dependent carbon monoxide dehydrogenase (CODH), which plays an important role in the global carbon cycle (12). The structure, along with that of an associated enzyme complex (13), provided a series of snapshots of the multiple metal ion centers underlying the ability of certain microbes to live off hydrogen gas and carbon dioxide in a process known as acetogenesis. More recently, they investigated the molecular basis by which the activity of CODH enzymes can be restored after oxygen exposure (14), a discovery with implications for the industrial use of CODHs.
Drennan and her team have also studied the organic compound methylphosphonate that was proposed as a source of methane from the aerobic upper ocean; the biological source was long a mystery. When a methylphosphonate synthase was discovered by chemical biologist Wilfred van der Donk and coworkers, part of the mystery was solved but the gene for this enzyme did not appear to be widespread. When Drennan and colleagues solved the structure of a methylphosphonate synthase; however, they discovered a sequence motif showing that the gene was, in fact, abundant in microbes that inhabit the upper ocean (15). This seminal finding is credited with resolving the oceanic methane paradox.
Radical-Based Chemistry in Ribonucleotide Reductases
Human RNR is an established chemotherapeutic target, and bacterial RNRs hold promise as antibiotic targets. So Drennan and her team have a longstanding interest in uncovering the mechanisms of RNRs. In 2002, her lab determined the structure of a B12-dependent RNR, which showed how cobalamin could be used to initiate radical chemistry (16). Nearly a decade later, Drennan’s team revealed how high levels of the nucleotide deoxyadenosine triphosphate (dATP) down-regulate RNR activity (17, 18). They subsequently provided structures showing the molecular basis of allosteric specificity, which maintains the proper ratios of RNA to DNA building blocks (19), and demonstrated the importance of RNR activity regulation (20).
An atomic-resolution structure of any RNR in an active state had been elusive for many years. Drennan and her team achieved the feat in 2020 when they trapped the active state of Escherichia coli RNR and determined its structure by cryoelectron microscopy (21). However, the resolution of the structure was too low for the visualization of water molecules believed to be critical in the radical transfer pathway.
In her IA, Drennan (1) describes how her team resolved the problem, presenting the structure of an active RNR at atomic resolution allowing for the visualization of water molecules. She explains, “This time, instead of using unnatural amino acids to trap the structure, we used a mechanism-based inhibitor. It was a very long road to get to these data, but it was worth the wait.”
“Superheroes of the Cell”
For her achievements, Drennan has received MIT’s Everett Moore Baker Memorial Award for Excellence in Undergraduate Teaching (2005, 2024), the Dorothy Crowfoot Hodgkin Award from The Protein Society (2020), and the William C. Rose Award from the American Society for Biochemistry and Molecular Biology (2023), among other honors. She has mentored nearly 100 undergraduates and dozens of graduate students and postdoctoral associates, many of whom are from underrepresented minority groups or disadvantaged backgrounds. She considers her students extended family members and takes pride in their accomplishments.
She and her team continue to work on RNR using the tools of structural biology. She says, “We want to obtain a deeper level of understanding of the human RNR, which is a cancer drug target. We also want to identify differences between the human enzyme and bacterial RNRs, differences that could be exploited in the development of new antibiotics.”
Beyond these efforts, Drennan’s overall goal is to understand how enzymes control radical species to enable challenging chemical reactions without damaging themselves or their cellular environment. “Radical enzymes are like the Avengers, powerful but with a high potential for collateral damage,” she explains. “I am fascinated by how nature catalyzes the most challenging of chemical reactions. The enzymes that do this work are the superheroes of the cell and I want to know their secrets.”
1.
D. E. Westmoreland et al., 2.6-Å resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N3CDP. Proc. Natl. Acad. Sci. U.S.A.121, e2417157121 (2024). Crossref. PubMed.
2.
C. L. Drennan et al., How a protein binds B12: A 3.0 Å X-ray structure of B12-binding domains of methionine synthase. Science266, 1669–1674 (1994). Crossref. PubMed.
3.
Y. Kung et al., Visualizing molecular juggling within a B12-dependent methyltransferase complex. Nature484, 265–269 (2012). Crossref. PubMed.
4.
F. A. Vaccaro, D. A. Born, C. L. Drennan, Structure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery. Proc. Natl. Acad. Sci. U.S.A.120, e2214085120 (2023). Crossref. PubMed.
5.
M. Jost et al., Structural basis for gene regulation by a B12-dependent photoreceptor. Nature526, 536–541 (2015). Crossref. PubMed.
6.
F. Berkovitch et al., Crystal structure of biotin synthase, an S-Adenosylmethionine-dependent radical enzyme. Science303, 76–79 (2004). Crossref. PubMed.
7.
J. L. Vey et al., Structural basis for glycyl radical formation by pyruvate formate-lyase activating enzyme. Proc. Natl. Acad. Sci. U.S.A.105, 16137–16141 (2008). Crossref. PubMed.
8.
J. Bridwell-Rabb et al., A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis. Nature544, 322–326 (2017). Crossref. PubMed.
9.
P. J. Goldman, T. L. Grove, S. J. Booker, C. L. Drennan, X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motifs for AdoMet radical chemistry. Proc. Natl. Acad. Sci. U.S.A.40, 15949–15954 (2013). Crossref.
10.
M. I. McLaughlin et al., Crystallographic snapshots of sulfur insertion by lipoyl synthase. Proc. Natl. Acad. Sci. U.S.A.113, 9446–9450 (2016). Crossref. PubMed.
11.
L. C. Blasiak, F. H. Vaillancourt, C. T. Walsh, C. L. Drennan, Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature440, 368–371 (2006). Crossref. PubMed.
12.
C. L. Drennan et al., Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase. Proc. Natl. Acad. Sci. U.S.A.98, 11973–11978 (2001). Crossref. PubMed.
13.
T. I. Doukov et al., A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase. Science298, 567–572 (2002). Crossref. PubMed.
14.
E. C. Wittenborn et al., Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide dehydrogenase. Elife7, e39451 (2018). Crossref. PubMed.
15.
D. A. Born et al., Structural basis for methylphosphonate biosynthesis. Science358, 1336–1339 (2017). Crossref. PubMed.
16.
M. D. Sintchak et al., The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer. Nat. Struct. Mol. Biol.9, 293–300 (2002). Crossref.
17.
N. Ando et al., Structural interconversions modulate activity of Escherichia coli ribonucleotide reductase. Proc. Natl. Acad. Sci. U.S.A.108, 21046–21051 (2011). Crossref. PubMed.
18.
N. Ando et al., Allosteric inhibition of human ribonucleotide reductase by dATP entails the stabilization of a hexamer. Biochemistry55, 373–381 (2016). Crossref. PubMed.
19.
C. M. Zimanyi et al., Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli. Elife5, e07141 (2016). Crossref. PubMed.
20.
P.Y.-T. Chen, M. A. Funk, E. J. Brignole, C. L. Drennan, Disruption of an oligomeric interface prevents allosteric inhibition of Escherichia coli class Ia ribonucleotide reductase. J. Biol. Chem.293, 10404–10412 (2018). Crossref. PubMed.
21.
G. Kang, A. T. Taguchi, J. Stubbe, C. L. Drennan, Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex. Science368, 424–427 (2020). Crossref. PubMed.
Understanding the Role of PARPs and UBF1 in Building Ribosomes
Noah Daly | Department of Biology
September 25, 2024
While pursuing her passion for research, BSG-MSRP-Bio student Adriana Camacho-Badillo made major contributions to research in the Calo Lab in the Department of Biology at MIT.
Growing up in Puerto Rico, Adriana Camacho-Badillo had no explanation for her recurrent multiple fracture injuries. In her teens, she was finally able to see a geneticist who diagnosed her with a genetic syndrome that affects connective tissue throughout the body.
This awakened an interest in genetics that led her to immerse herself in her genetic panel results, curious about the role of each gene that was tested.
“I realized I wanted to find out how mutations affect gene expression that could possibly lead to a distinct phenotype or even a genetic syndrome,” she says.
Within a few years of setting her sights on becoming a scientist, Camacho-Badillo began her first research experience working in the laboratory of Professors Hector Areizaga-Martínez and Elddie Román-Morales. Her work focused on experiments using enzymes to degrade Dichloro-diphenyl-trichloroethane, or DDT, a once-common pesticide known to be highly toxic to humans and other mammals that remains in the environment long after application to crops.
As she became familiar with the day-to-day routines of designing and executing research experiments, she realized she was drawn to biochemistry and molecular biology. Camacho-Badillo soon applied to the molecular neuroscience lab of Professor Miguel Méndez at the University of Puerto Rico at Aguadilla and joined their team working on the effects of high glucose in the central nervous system of mice.
Expanding Experiences While Narrowing Focus
When Camacho-Badillo was sixteen, alongside Méndez and other students, she participated in the Quantitative Methods Workshop at MIT. The workshop allows undergraduate students from universities around the United States and the Caribbean to come together for a few days in January to learn how to apply computational tools that can help biological research.
One of the sessions she attended was a talk about machine learning and studying the brain, presented by graduate student Taylor Baum.
“I loved Taylor’s workshop,” Camacho-Badillo said, “When Taylor asked if anyone would be interested in volunteering to teach Spanish-speaking students in grade school science, I said yes without hesitation.”
Baum, a neuroscientist and computer scientist working in the Munther Dahleh Research Group at MIT, is also the founder of Sprouting, Inc. The organization equips high-school students and undergraduates in Puerto Rico with STEM skills to help them pursue careers in science and technology.
The BSG-MSRP-Bio program offers lab experience and extracurricular activities such as journal clubs and dinners with professors. At one of these events, she met Associate Professor of Biology Eliezer Calo.
“I loved meeting another scientist from Puerto Rico working on molecular biology, so I decided to look further into his research,” Camacho-Badillo recalls.
In 2024, she was delighted to have the opportunity to return to the BSG-MSRP-Bio Program for a second time, and now to work in Calo’s Lab.
The Unsolved Mysteries of UBF1
Although BSG-MSRP-Bio students are often mentored by graduate students or postdocs, Calo spent the summer mentoring Camacho-Badillo directly. As an alumnus of the MSRP-Bio program himself, Calo understands firsthand how much of an impact meaningful research can have for an undergraduate student spending a few months experiencing life in the lab at MIT.
In the Calo Lab, Camacho-Badillo spent the early days of this summer poring over past research papers on genetic transcription, trying to answer a big question in molecular biology. Camacho-Badillo has been helping Calo understand how a particular protein affects the production of ribosomes in cells.
A ribosome is the molecular machinery that synthesizes proteins, and an average cell can produce around 10 million ribosomes to sustain its essential functions. Creating these protein engines requires the transcription of ribosomal DNA, or rDNA.
In order to synthesize RNA, specific proteins called polymerases must bind to the DNA. Camacho-Badillo’s work focuses on one of those binding proteins called upstream binding factor, or UBF1. UBF1 is essential for the synthesis of the ribosomal RNA. The UBF1 transcription factor is responsible for recruiting the polymerase, RNA polymerase I, to transcribe the rDNA into rRNA.
Despite knowing the importance of UBF1 in ribosomal production, it’s unclear what its full purpose is in this process. Calo and Camacho-Badillo think that clarifying the role of UBF1 in ribosomal biogenesis will help scientists understand how certain neurological diseases occur. UBF1 is known to be associated with diseases such as acute myeloid leukemia and childhood-onset neurodegeneration with brain atrophy, but the mechanism is not yet understood.
UBF1 is a peculiar transcription factor. Before it can transcribe a gene, UBF1 must first dimerize, forming a bond with another UBF1 protein. After binding to the rDNA, UBF1 can recruit the remaining RNA transcription machinery. The dimer is crucial for transcription to occur, yet this protein can make further connections with other UBF1 monomers, a process called oligomerization.
Nothing is concretely understood about how oligomers of UBF1 form: they could be critical for transcription, forming clusters that can no longer bind with rDNA or inhibit the recruitment of the remaining RNA transcription machinery. These clusters could also be directly contributing to a variety of neurological diseases.
“The genome contains multiple rDNA copies, but not all are utilized,” Calo explains. “UBF1 must precisely identify the correct copies to activate while avoiding the formation of aggregates that could impair its function.”
The regulation of these dimers is also a mystery. Early in the summer, Camacho-Badillo helped make an important connection: prior research from the Calo Lab showed that enzymes called poly ADP-ribose polymerases, or PARPs, play a role in maintaining chemical properties in the nucleolus, where ribosomes are produced and assembled. The main target of these proteins within the RNA transcriptional machinery before transcription is initiated is UBF1.
Based on this initial result, Camacho-Badillo’s entire summer project shifted to further characterize PARPs in ribosome biogenesis.
“This observation about the role PARPs plays is a big deal for us,” Calo says. “We do many experiments in my lab, but Adriana’s work this summer has opened a key gateway to understanding the mysteries behind UBF1 regulation, leading to proper ribosome production and allowing the Calo lab to pursue this goal. She’s going to be a superstar.”
Camacho-Badillo’s work hasn’t ended with the BSG-MSRP-Bio program, however. She’ll spend the fall semester at MIT, continuing to work on understanding how rDNA transcription is regulated as a visiting student in the Calo Lab. Although she still has a year and a half to go in her undergraduate degree, she’s already set her sights on graduate school.
“This program has meant so much to me and brought so much into my life,” she says. “All I want to do right now is keep this research going.”
All It takes to titer: discovering a love of troubleshooting at MIT
Noah Daly | Department of Biology
September 25, 2024
BSG-MSRP-Bio student Yeongseo Son breathed new life into her love of science over the summer in the Spranger Lab studying immune responses in the lung in the Department of Biology at MIT.
Back home at the University of Georgia, Son studies neutrophils, a kind of innate immune cell that serves as the body’s first line of defense against foreign pathogens. After taking a graduate-level course on immunology last semester, Son realized she needed to increase her basic understanding of the broad discipline.
“I knew that coming to work with Professor Spranger would give me a chance to work on cancer immunology and T cell biology, two really cool and important fields I haven’t been exposed to,” Son says.
It took several attempts from the Senior Lecturer and BSG-MSRP-Bio program coordinator Mandana Sassanfar to reach her before Son accepted.
“Before I arrived, I was worried it would be too intense or that I wouldn’t fit in,” Son says. “I couldn’t have been more wrong: yes, the work is challenging, but everyone is here because they truly love science.”
This quest involved multiple steps, such as culturing cells, infecting the cells with the virus, and measuring how lethal it is to host cells, working with a strain that her lab hadn’t used before.
To test the strength of the virus, the virus is mixed with host cells in order to infect them. Then the host cells are placed on a layer of agar, a gelatinous substance that provides nutrients for the host cells. When a virus-infected cell dies, it creates a hole in the layer of cells called a plaque. The number of plaques is recorded to determine the virus’s titer, or frequency.
Son excitedly executed her plaque assay after breezing through the first two steps. The next day, to her surprise and disappointment, all her cells — including the negative control — had died.
“The first time it failed, I was crushed because I had written the protocol over and over,” Son says.
That initial disappointment, however, turned into excitement to solve the problem. She worked closely with her mentor, Postdoc Taylor Heim, who helped motivate her to keep trying to figure out what had gone wrong.
Son spent weeks designing a process to effectively titer the virus. She laid out a plan of action to assess what could be toxic to the cells and systematically tested each component of the protocol that could affect the growth of her strain of influenza.
It took Son four attempts before she had a eureka moment: the success of her cell cultures depended on the precise measurement of just one reagent.
Too much of the reagent meant the cells would all die on arrival, but just a little bit, and they would survive. It took Son three more attempts — seven experiments in total — to fully ensure the success of the assay.
Throughout this process, and despite her many failures, Son realized she finds troubleshooting very enjoyable. Each failure was unique and crucial for her eventual success.
“I’m making a difference — I’m figuring something out that can really help with future experiments,” Son says. “That moment of success is why I gained such confidence in being a scientist.”
Lighting Up the Lungs
In the Spranger Lab, Son’s other summer project focused on the respiratory system. She was examining a type of specialized cell called resident memory CD8+ T cells in the lungs and lymph nodes of mice infected with influenza. These specialized T cells gain a kind of memory of how to fight off a virus and remain in the lungs and lung-draining lymph node tissues long after the tissues have overcome the immune challenge of something like influenza.
Son’s postdoctoral student mentor Taylor Heim is especially interested in the potential of these cells for cancer immunotherapy.
To better understand how the resident memory T cell populations change over time, Son and Heim conducted a time-point experiment in which mice were studied at different points after being infected with influenza. They do this by injecting antibodies into the mouse’s bloodstream after infection, which mark any immune cells circulating in the blood, allowing the researchers to gauge if the cells are recruited to help fight a virus.
Son’s work this summer goes deeper, examining proteins known as cytokines that enable the immune system to combat germs or other substances that can harm an organism.
Son used a genetically modified mouse to track the production of interferon-gamma, IFN‐γ. IFN‐γ is a cytokine that plays a key role in regulating immune responses, often helping fight off infection and cancer. Son found evidence that resident memory T cells produce this cytokine in both the lungs and lung-draining lymph nodes.
The goal of this research is to one day use the information collected on resident memory CD8+ T cell populations and cytokine expression to help systematically target cancerous cells that appear in the body.
“Yeongseo has helped us pioneer a system to track how these cells move within tissues of living mice,” Spranger explains. “By using this approach, we will be able to understand how they are affecting cancer development and how cancer is affecting them, and that’s pretty exciting.”
Learning Outside the Lab
The BSG-MSRP-Bio program also gave Son near-constant access to faculty from across the biology department, both through extracurricular offerings such as dinner seminars and journal clubs as well as departmental retreats.
She’s also sat down with professors individually and heard more about their stories and research as part of her podcast Let’s Talk Chemistry. Nobel Laureate Phil Sharp, whose office is on the same floor as the Spranger Lab, joined the show after Son dropped by his office to introduce herself. Son learned more about his discoveries in RNA splicing and the behind-the-scenes details of his Nobel Prize ceremonies.
At MIT, Son has found a welcoming community of enthusiastic scientists working towards common goals, especially in her lab. Every day, members of the Spranger Lab actively seek each other out to have lunch together, and she feels right at home with them.
“I realized that yes, the people in this community are intensely passionate about their work, but they’re also multi-dimensional with a ton of different interests,” Son says. “One of the graduate students in my lab even gave me tennis lessons, and I’m already a better player because of it.”
As she returns to her studies in Georgia and begins the process of applying to graduate schools, Son is excited about her future in science. Armed with new knowledge, confidence, and community, she’s ready for whatever curveball her career in science will throw her next.
A scientist’s toolkit: practice, patience, and plenty of questions
Noah Daly | Department of Biology
September 24, 2024
A childhood interest in the complex worlds within an organism that the naked eye cannot see ultimately led Praise Lasekan to the BSG-MSRP-Bio program at MIT working in the Vos Lab in the Department of Biology at MIT.
Praise Lasekan talks about the fast protein liquid chromatography machines he used in the Vos Lab as though they were colleagues.
“We have two of them,” he explains. “Sam and Frodo.”
FPLC machines separate and analyze proteins based on their properties, such as size, charge, and binding affinity. When Lasekan first saw the FPLC machines, the tubing and valves, hooked up to a computer, reminded him of a fancy piece of plumbing. Much like an expert plumber, proficiency with these machines required him to understand every valve and tube.
Although Lasekan is a Biology major with a Chemistry Minor at the University of Maryland, Baltimore County, Lasekan had the opportunity to spend his summer living in Boston and working on MIT’s campus as a Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology student.
“I loved every part of this summer: Waking up in the morning, coming to the lab, setting up some stuff — whether it goes well or not,” Lasekan says. “Taking that experience and coming back the next day, you’re ready to keep going and improving.”
Lasekan spent his days in the lab of Seychelle Vos, Robert A. Swanson Career Development Professor of Life Sciences and HHMI Freeman Hrabowski Scholar. The Vos Lab examines how genetic information is stored so compactly yet is still accessible enough for genes to be expressed. All cells in an organism have the same DNA, but the organization of that DNA and how genes are expressed determine why one cell becomes part of the liver and another cell part of the brain.
Lasekan worked with a highly conserved protein that plays a role in gene transcription called CCCTCF-binding factor, or CTCF. He worked to understand how adding a phosphate group, a process called phosphorylation, affects CTCF’s binding to DNA. Binding to DNA is the first step in the process of transcription, which creates proteins within a cell.
The Vos lab uses various tools and techniques that Vos learned during her training, often using simple systems with limited components to study phenomena such as molecular structures, the dynamics of proteins and nucleic acids, and how structural alterations affect the function of these molecules. The lab has also recently been delving into more systemic work, such as removing genes from cells to observe how that affects gene expression.
“My lab is a little unconventional in some ways,” Vos says. “We use a lot of biochemistry and structural biology, but we want to use the tools of genetics and cell biology as well to understand how genome organization and genome expression are coupled.”
CTCF can play many roles during transcription, able to act as an activator or as a roadblock for transcription. Lasekan’s mentor, graduate student Bonnie Su, has been trying to figure out how cells control CTCF behavior.
“What if the cell needed something done ASAP, and CTCF was blocking its route to its destination on a DNA sequence?” Vos asks. “How does the cell regulate it?”
Praise mutated different sites on CTCF that have been reported in previous research as possible points of phosphorylation of the CTCF protein. Several other amino acids can also be phosphorylated. Still, Su was particularly interested in the work other researchers have done on three specific sites along a segment called the zinc finger domain. A zinc finger domain is a zinc ion that helps proteins stabilize their shape and the domain has a function in various cellular processes such as genetic transcription. The ion is regulated by amino acids to give it a finger-like structure that helps in binding the protein to DNA during transcription.
“Before we went on a wild goose chase,” Lasekan explains, “we needed to identify a specific area of the protein to concentrate on and examine the behavior of CTCF locally there.”
Off of the Drawing Board and Into the Laboratory
Lasekan was introduced to the microscopic world of the body — cells, organelles, molecules, and even atoms — in the pages of his secondary school science textbooks in Ondo, Nigeria. There began his curiosity about atomic structures, cells, and the complex worlds within an organism that the naked eye cannot see. He would spend much of his class time flipping through the pages of diagrams and ultimately decided to pursue science as his core focus during senior secondary school.
“It was there that I could take my first classes in chemistry, biology, and physics,” he says. “I realized I love all of the sciences, so my focus in school was science and technology.”
Initially drawn to engineering, Lasekan ended up dropping out of a technical drawing course.
“I loved the course,” Lasekan smiles, “but the course didn’t like me one bit.”
Lasekan’s dreams shifted toward medicine and, with it, more science and math courses.
When he graduated valedictorian from Staff Secondary School at the Federal University of Technology in Akure, his parents — both pharmacists — encouraged him to apply to university to become a medical doctor. However, getting into a good university is challenging in Nigeria.
Praise opted instead to remain at home after graduating, building a successful business doing portrait photography. He also took chemistry, physics, and biology courses through Cambridge University International.
Despite making good money with photography, Praise was determined to go to university but wasn’t confident that he would get in. Nevertheless, an acquaintance encouraged him to apply to UMBC.
“It was the only school I applied to, and I couldn’t believe that I got in,” says Lasekan.
At UMBC, Lasekan discovered the pre-med track he’d signed up for was not a good fit for him either — many of the fundamental questions he was curious about were beyond the scope of his courses. A friend who was working in a research lab on campus suggested that Lasekan should try to find a lab to work in, too.
“They told me I might like what they’re doing there because of the level of questions that I ask,” Lasekan says. “Sometimes people didn’t have answers for me, and maybe I could find some of those answers through research.”
Dr. Green focuses on trying to understand how post-translational modifications of proteins regulate functions, such as the establishment of proper states of gene expression and the ability of cells to respond to stress.
“Dr. Green took a chance with me,” Lasekan says. “I am forever grateful to her for that.”
MIT: A Destination for Scientific Discovery
When considering summer research programs, Praise applied to MIT, one institution he’d always remembered from his childhood textbooks as the birthplace of many great inventions and scientific discoveries.It’s also one of the few programs in the U.S. that accepts international students.
“I’ve always had MIT at the back of my mind, but I didn’t think they’re looking for people like me,” Lasekan says. When he saw the notification for his acceptance to the program pop up on his smartwatch, he screamed, startling some students walking by him in the hallway.
“This is one of the best institutions in the world, and I just got an opportunity to go there for ten weeks, actually do a project of my own under the mentorship of my PI,” Lasekan recalls thinking. “This was a dream come true for me.”
In the Vos lab, Lasekan’s interest in the fundamental questions of biology was not only acceptable but encouraged, especially by his mentor, Su.
“Bonnie always had the patience to sit down with me, explain concepts to me, and write out the math with me if I need her to,” Lasekan says, “and sometimes I need it 25 times, but she’s there for me.”
Now that the BSG-MSRP-Bio program has wrapped up, Praise has the confidence to set his sights higher than ever before — on the “big guys,” the universities and institutions doing the sort of cutting-edge research that first caught his eye in the textbooks back home. Praise is eagerly preparing his graduate school applications for fall 2025, including MIT.
“After being here, surrounded by people from everywhere driven by the same purpose, I know there’s an exciting future in science for me.”
At the cutting edge of pedagogy, Mary Ellen Wiltrout has shaped blended and online learning at MIT and beyond.
Samantha Edelen | Department of Biology
September 18, 2024
When she was a child, Mary Ellen Wiltrout PhD ’09 didn’t want to follow in her mother’s footsteps as a K-12 teacher. Growing up in southwestern Pennsylvania, Wiltrout was studious with an early interest in science — and ended up pursuing biology as a career.
But following her doctorate at MIT, she pivoted toward education after all. Now, as the director of blended and online initiatives and a lecturer with the Department of Biology, she’s shaping biology pedagogy at MIT and beyond.
Establishing MOOCs at MIT
To this day, E.C. Whitehead Professor of Biology and Howard Hughes Medical Institute (HHMI) investigator emeritus Tania Baker considers creating a permanent role for Wiltrout one of the most consequential decisions she made as department head.
Since launching the very first MITxBio massive online open course 7.00x (Introduction to Biology – the Secret of Life) with professor of biology Eric Lander in 2013, Wiltrout’s team has worked with MIT Open Learning and biology faculty to build an award-winning repertoire of MITxBio courses.
MITxBio is part of the online learning platform edX, established by MIT and Harvard University in 2012, which today connects 86 million people worldwide to online learning opportunities. Within MITxBio, Wiltrout leads a team of instructional staff and students to develop online learning experiences for MIT students and the public while researching effective methods for learner engagement and course design.
“Mary Ellen’s approach has an element of experimentation that embodies a very MIT ethos: applying rigorous science to creatively address challenges with far-reaching impact,” says Darcy Gordon, instructor of blended and online initiatives.
Mentee to motivator
Wiltrout was inspired to pursue both teaching and research by the late geneticist Elizabeth “Beth” Jones at Carnegie Mellon University, where Wiltrout earned a degree in biological sciences and served as a teaching assistant in lab courses.
“I thought it was a lot of fun to work with students, especially at the higher level of education, and especially with a focus on biology,” Wiltrout recalls, noting she developed her love of teaching in those early experiences.
Though her research advisor at the time discouraged her from teaching, Jones assured Wiltrout that it was possible to pursue both.
Jones, who received her postdoctoral training with late Professor Emeritus Boris Magasanik at MIT, encouraged Wiltrout to apply to the Institute and join American Cancer Society and HHMI Professor Graham Walker’s lab. In 2009, Wiltrout earned a PhD in biology for thesis work in the Walker lab, where she continued to learn from enthusiastic mentors.
“When I joined Graham’s lab, everyone was eager to teach and support a new student,” she reflects. After watching Walker aid a struggling student, Wiltrout was further affirmed in her choice. “I knew I could go to Graham if I ever needed to.”
After graduation, Wiltrout taught molecular biology at Harvard for a few years until Baker facilitated her move back to MIT. Now, she’s a resource for faculty, postdocs, and students.
“She is an incredibly rich source of knowledge for everything from how to implement the increasingly complex tools for running a class to the best practices for ensuring a rigorous and inclusive curriculum,” says Iain Cheeseman, the Herman and Margaret Sokol Professor of Biology and associate head of the biology department.
Stephen Bell, the Uncas and Helen Whitaker Professor of Biology and instructor of the Molecular Biology series of MITxBio courses, notes Wiltrout is known for staying on the “cutting edge of pedagogy.”
“She has a comprehensive knowledge of new online educational tools and is always ready to help any professor to implement them in any way they wish,” he says.
Gordon finds Wiltrout’s experiences as a biologist and learning engineer instrumental to her own professional development and a model for their colleagues in science education.
“Mary Ellen has been an incredibly supportive supervisor. She facilitates a team environment that centers on frequent feedback and iteration,” says Tyler Smith, instructor for pedagogy training and biology.
Prepared for the pandemic, and beyond
Wiltrout believes blended learning, combining in-person and online components, is the best path forward for education at MIT. Building personal relationships in the classroom is critical, but online material and supplemental instruction are also key to providing immediate feedback, formative assessments, and other evidence-based learning practices.
“A lot of people have realized that they can’t ignore online learning anymore,” Wiltrout noted during an interview on The Champions Coffee Podcast in 2023. That couldn’t have been truer than in 2020, when academic institutions were forced to suddenly shift to virtual learning.
“When Covid hit, we already had all the infrastructure in place,” Baker says. “Mary Ellen helped not just our department, but also contributed to MIT education’s survival through the pandemic.”
For Wiltrout’s efforts, she received a COVID-19 Hero Award, a recognition from the School of Science for staff members who went above and beyond during that extraordinarily difficult time.
“Mary Ellen thinks deeply about how to create the best learning opportunities possible,” says Cheeseman, one of almost a dozen faculty members who nominated her for the award.
Recently, Wiltrout expanded beyond higher education and into high schools, taking on several interns in collaboration with Empowr, a nonprofit organization that teaches software development skills to Black students to create a school-to-career pipeline. Wiltrout is proud to report that one of these interns is now a student at MIT in the class of 2028.
Looking forward, Wiltrout aims to stay ahead of the curve with the latest educational technology and is excited to see how modern tools can be incorporated into education.
“Everyone is pretty certain that generative AI is going to change education,” she says. “We need to be experimenting with how to take advantage of technology to improve learning.”
Ultimately, she is grateful to continue developing her career at MIT biology.
“It’s exciting to come back to the department after being a student and to work with people as colleagues to produce something that has an impact on what they’re teaching current MIT students and sharing with the world for further reach,” she says.
As for Wiltrout’s own daughter, she’s declared she would like to follow in her mother’s footsteps — a fitting symbol of Wiltrout’s impact on the future of education.
For Sarah Sterling, the new director of the Cryo-Electron Microscopy facility at MIT.nano, better planning and more communication leads to better science.
Nikole L. Fendler | Department of Biology
September 6, 2024
Sarah Sterling, director of the Cryo-Electron Microscopy, or Cryo-EM, core facility, often compares her job to running a small business. Each day brings a unique set of jobs ranging from administrative duties and managing facility users to balancing budgets and maintaining equipment.
Although one could easily be overwhelmed by the seemingly never-ending to-do list, Sterling finds a great deal of joy in wearing so many different hats. One of her most essential tasks involves clear communication with users when the delicate instruments in the facility are unusable because of routine maintenance and repairs.
“Better planning allows for better science,” Sterling says. “Luckily, I’m very comfortable with building and fixing things. Let’s troubleshoot. Let’s take it apart. Let’s put it back together.”
Out of all her duties as a core facility director, she most looks forward to the opportunities to teach, especially helping students develop research projects.
“Undergraduate or early-stage graduate students ask the best questions,” she says. “They’re so curious about the tiny details, and they’re always ready to hit the ground running on their projects.”
A non-linear scientific journey
When Sterling enrolled in Russell Sage College, a women’s college in New York, she was planning to pursue a career as a physical therapist. However, she quickly realized she loved her chemistry classes more than her other subjects. She graduated with a bachelor of science degree in chemistry and immediately enrolled in a master’s degree program in chemical engineering at the University of Maine.
Sterling was convinced to continue her studies at the University of Maine with a dual PhD in chemical engineering and biomedical sciences. That decision required the daunting process of taking two sets of core courses and completing a qualifying exam in each field.
“I wouldn’t recommend doing that,” she says with a laugh. “To celebrate after finishing that intense experience, I took a year off to figure out what came next.”
Sterling chose to do a postdoc in the lab of Eva Nogales, a structural biology professor at the University of California at Berkeley. Nogales was looking for a scientist with experience working with lipids, a class of molecules that Sterling had studied extensively in graduate school.
At the time Sterling joined, the Nogales Lab was at the forefront of implementing an exciting structural biology approach: cryo-EM.
“When I was interviewing, I’d never even seen the type of microscope required for cryo-EM, let alone performed any experiments,” Sterling says. “But I remember thinking ‘I’m sure I can figure this out.’”
Cryo-EM is a technique that allows researchers to determine the three-dimensional shape, or structure, of the macromolecules that make up cells. A researcher can take a sample of their macromolecule of choice, suspend it in a liquid solution, and rapidly freeze it onto a grid to capture the macromolecules in random positions — the “cryo” part of the name. Powerful electron microscopes then collect images of the macromolecule — the EM part of cryo-EM.
The two-dimensional images of the macromolecules from different angles can be combined to produce a three-dimensional structure. Structural information like this can reveal the macromolecule’s function inside cells or inform how it differs in a disease state. The rapidly expanding use of cryo-EM has unlocked so many mechanistic insights that the researchers who developed the technology were awarded the 2017 Nobel Prize in Chemistry.
The MIT.nano facility opened its doors in 2018. The open-access, state-of-the-art facility now has more than 160 tools and more than 1,500 users representing nearly every department at MIT. The Cryo-EM facility lives in the basement of the MIT.nano building and houses multiple electron microscopes and laboratory space for cryo-specimen preparation.
Thanks to her work at UC Berkeley, Sterling’s career trajectory has long been intertwined with the expanding use of cryo-EM in research. Sterling anticipated the need for experienced scientists to run core facilities in order to maintain the electron microscopes needed for cryo-EM, which range in cost from a staggering $1 million to $10 million each.
After completing her postdoc, Sterling worked at the Harvard University cryo-EM core facility for five years. When the director position for the MIT.nano Cryo-EM facility opened, she decided to apply.
“I like that the core facility at MIT was smaller and more frequently used by students,” Sterling says. “There’s a lot more teaching, which is a challenge sometimes, but it’s rewarding to impact someone’s career at such an early stage.”
A focus on users
When Sterling arrived at MIT, her first initiative was to meet directly with all the students in research labs that use the core facility to learn what would make using the facility a better experience. She also implemented clear and standard operating procedures for cryo-EM beginners.
“I think being consistent and available has really improved users’ experiences,” Sterling says.
The users themselves report that her initiatives have proven highly successful — and have helped them grow as scientists.
“Sterling cultivates an environment where I can freely ask questions about anything to support my learning,” says Bonnie Su, a frequent Cryo-EM facility user and graduate student from the Vos lab.
But Sterling does not want to stop there. Looking ahead, she hopes to expand the facility by acquiring an additional electron microscope to allow more users to utilize this powerful technology in their research. She also plans to build a more collaborative community of cryo-EM scientists at MIT with additional symposia and casual interactions such as coffee hours.
Under her management, cryo-EM research has flourished. In the last year, the Cryo-EM core facility has supported research resulting in 12 new publications across five different departments at MIT. The facility has also provided access to 16 industry and non-MIT academic entities. These studies have revealed important insights into various biological processes, from visualizing how large protein machinery reads our DNA to the protein aggregates found in neurodegenerative disorders.
If anyone wants to conduct cryo-EM experiments or learn more about the technique, Sterling encourages anyone in the MIT community to reach out.
“Come visit us!” she says. “We give lots of tours, and you can stop by to say hi anytime.”
Renee Barbosa, a Schimmel scholar and a graduate student in the Soto-Feliciano Lab, uses a multidisciplinary approach to understand the epigenetic factors in gene expression.
Bendta Schroeder | Koch Institute
July 29, 2024
Professor Emeritus of Biology Paul Schimmel PhD ’67 and his wife Cleo Schimmel are among the biggest champions and supporters of graduate students conducting life science research in the Department of Biology at MIT, as well as in departments such as the Department of Brain and Cognitive Sciences, the Department of Biological Engineering, and the Department of Chemistry, and in cross-disciplinary degree programs including the Computational and Systems Biology Program, the Molecular and Cellular Neuroscience Program, and the Microbiology Graduate Program. In addition to the Cleo and Paul Schimmel (1967) Scholars Fund to support graduate women students in the Department of Biology, in 2021, the Schimmels established the MIT Schimmel Family Program for Life Sciences.
Their generous pledge of $50 million in matching funds called for other donors to join them in supporting the training of graduate students who will tackle some of the world’s most urgent challenges. Driven by their unwavering belief that graduate studentsare the driving force behind much life science research and witnessing a decline in federal funding for graduate education, the Schimmel family established their one-to-one match program. They reached the ambitious goal of $100 million in endowed support in just two years.
The discovery that mutations in genes can drive cancer revolutionized cancer research. In the decades following the identification of the first “oncogene” in a chicken retrovirus in 1970 and the first human oncogene in 1982 by Robert Weinberg at MIT’s Center for Cancer Research, scientists uncovered hundreds more oncogenes, transformed our understanding of how cancer begins and progresses, and developed sophisticated gene-targeted cancer therapies.
A majority of oncogenes were identified in factors controlling cell signaling, proliferation, and differentiation. However, a growing understanding of epigenetics has shown that many cancers, such as some leukemias and sarcomas, are not driven by mutations to these factors themselves, but by disruptions to the molecular pathways that regulate their expression. About 10 percent of all leukemias are driven by abnormal versions of the protein MLL1, one cog in the epigenetic machinery controlling these factors.
Renee Barbosa, a graduate student in the laboratory of Howard S. (1953) and Linda B. Stern Career Development Professor Yadira Soto-Feliciano in the Department of Biology, is joining this next wave of research, using leukemia as a model. A member of MIT’s Koch Institute for Integrative Cancer Research, Soto-Feliciano and her lab study chromatin, the densely coiled structures of DNA and scaffolding proteins that make up our genomes and help ensure genes are expressed at the right times and in the right amounts.
Barbosa focuses on the role of RNA processing and the precisely choreographed alterations to chromatin that govern gene expression. RNA molecules serve as messengers between DNA and its final product, protein, and are subject to extensive processing and regulation. However, not much is known about the interplay between RNA processing and epigenetic machinery, particularly in cancer.
“I hope that my work will uncover additional layers of complexity in the dynamic landscape of gene regulation,” says Barbosa. “It might also identify new mechanisms that can be targeted to help treat leukemia and other cancers.”
Before Barbosa arrived at the Soto-Feliciano Lab, she was already steeped in the molecular intricacies of cancer.
While at the University of Pennsylvania, she earned a BA in biochemistry and biophysics concurrently with a master’s degree in chemistry. Early on, she joined the lab of Ronen Marmorstein, which used molecular approaches to characterize MEK and ERK, two cancer-relevant members of a class of signaling proteins. Upon starting graduate school, she was excited to branch out into other disciplines.
Barbosa has always taken every opportunity she can to learn. Beginning in grade school, science and math were her favorite subjects, but she also explored music, dance, and foreign languages. At the University of Pennsylvania, she even squeezed in a minor in neuroscience.
With its interdisciplinary approach, the Soto-Feliciano Lab provides Barbosa ample opportunities to learn. Because epigenetic factors can elude traditional approaches, the Soto-Feliciano Lab uses a multidisciplinary strategy, ranging from molecular, to large-scale omics analyses, to disease modeling.
“When I was a grad student, we saw the arrival of powerful new massive sequencing and gene editing technologies — and were enabled to ask big new questions,” says Soto- Feliciano. “I am excited that Renee will have even more resources and opportunities, as we enter the next stage of cancer genetics and epigenetics.”
With the support of a Schimmel Fellowship, Barbosa will be ready to take advantage of new developments in her field.
“Support for research early on in graduate school is an incredible opportunity,” says Barbosa. “It means time to delve deep into the literature of the field and identify challenging open questions that I can pursue in my project. Though exploring these unknown areas requires taking bigger risks, I hope that we will get invaluable insight from an understanding of these nuanced and complex mechanisms.”
Graduate student and Schimmel Scholar Annette Jun Diao uses a minimal system to parse the mechanisms underlying gene expression
Lillian Eden | Department of Biology
July 29, 2024
Professor Emeritus of Biology Paul Schimmel PhD ’67 and his wife Cleo Schimmel are among the biggest champions and supporters of graduate students conducting life science research in the Department of Biology at MIT, as well as in departments such as the Department of Brain and Cognitive Sciences, the Department of Biological Engineering, and the Department of Chemistry, and in cross-disciplinary degree programs including the Computational and Systems Biology Program, the Molecular and Cellular Neuroscience Program, and the Microbiology Graduate Program. In addition to the Cleo and Paul Schimmel (1967) Scholars Fund to support graduate women students in the Department of Biology, in 2021, the Schimmels established the MIT Schimmel Family Program for Life Sciences.
Their generous pledge of $50 million in matching funds called for other donors to join them in supporting the training of graduate students who will tackle some of the world’s most urgent challenges. Driven by their unwavering belief that graduate studentsare the driving force behind much life science research and witnessing a decline in federal funding for graduate education, the Schimmel family established their one-to-one match program. They reached the ambitious goal of $100 million in endowed support in just two years.
Annette Jun Diao’s mother loves to tell the story of Diao’s childhood aversion to the study of life — the gross and the squishy. Unlike some future biologists, Diao wasn’t the type to stomp through creeks or investigate the life of frogs. Instead, she was interested in astronomy and only ended up in a high school biology class because of a bureaucratic snafu. The physics course she’d been hoping to take was canceled due to low enrollment, and she was informed molecular biology was being offered instead.
She attended the University of Toronto and joined the molecular genetics department because of the numerous opportunities for hands-on research. She’s now a third-year graduate student in the Department of Biology at MIT.
“I’m fascinated by the mechanisms that underlie the regulation of gene expression,” Diao says. “All of our genetic information is in DNA, and that DNA is an actual molecule with chemical properties that allow it to be passed from one generation to the next.”
Every cell in our bodies contains a genome of approximately 20,000 genes, but the cells in our retinas are vastly different than the cells in our hearts — not all genes are in action simultaneously, and cell fates vary depending on how which genes are active.
“What is really awesome about the department — and what was attractive to me when I was applying to graduate school — is that I wasn’t sure exactly what methods I wanted to use to answer the questions I was interested in,” Diao says. “A huge advantage of the program was that I had a lot to choose from.”
Diao chose to pursue her thesis work with Seychelle Vos, the Robert A. Swanson (1969) Career Development Professor of Life Sciences and HHMI Freeman Hrabowski Scholar. Diao has been recognized with a Natural Sciences and Engineering Research Council of Canada Fellowship, which is similar to a National Science Foundation graduate fellowship in the United States.
Vos’s lab is generally interested in understanding how transcription is regulated, the interplay of genome organization and gene expression, and the molecular machinery involved. Diao has been working with an enzyme called RNA polymerase II (RNAP II), the molecular machine that reads DNA and creates an RNA copy called mRNA. That mRNA goes on to be read by ribosomes to create proteins.
Many questions remain about RNAP II, including what signals instruct it to begin transcription and, once engaged, whether it will transcribe and how quickly it moves.
RNAP II doesn’t work alone. Diao is working to understand how a transcription factor called negative elongation factor associates with RNAP II and whether the DNA sequence affects that interaction.
Within the broader context of the genome, DNA is packaged extremely tightly; if it were allowed to unfold, its total length could stretch from Cambridge to Connecticut. What RNAP II has access to at any given time is therefore quite restricted, which Diao is also exploring.
She has been exploring this topic in what she refers to as a “reductionist approach.” By creating a minimal system — a strand of DNA and the precise addition of certain other isolated components — she can potentially parse out what ingredients and what sequence of events are essential “in order to really get to the nitty-gritty of how genes are regulated.”
Outside of her work in the lab, Diao is part of BioREFS, a peer support group for graduate students, and gwiBio. Both organizations bring members of the department together for scientific talks and socializing activities outside of the lab, and gwiBio also participates in community outreach.
Diao is also a Schimmel Scholar, supported by Professor Emeritus of Biology Paul Schimmel PhD ’67 and his wife Cleo Schimmel.
“It was really great to learn that I was being supported by a scientist who has done a lot of awesome work that’s relevant to my world,” Diao says.
“It is awesome that they are so committed to supporting the graduate program at MIT, especially when federal resources have become more limited,” Vos says. “With their support, our lab can train basic scientists who can then use their knowledge to transform our study of disease. I hope others follow Paul and Cleo’s example.”
Amulya Aluru ’23, MEng ’24 and the MIT Spokes have spent the summer spreading science, over 3,000 miles on two wheels.
Lillian Eden | Department of Biology
August 22, 2024
Amulya Aluru ’23, MEng ’24, will head to the University of California at Berkeley for a PhD in molecular and cell biology PhD this fall. Aluru knows her undergraduate 6-7 major and MEng program, where she worked on a computational project in a biology lab, have prepared her for the next step of her academic journey.
“I’m a lot more comfortable with the unknown in terms of research — and also life,” she says. “While I’ve enjoyed what I’ve done so far, I think it’s equally valuable to try and explore new topics. I feel like there’s still a lot more for me to learn in biology.”
Unlike many of her peers, however, Aluru won’t reach the San Francisco Bay Area by car, plane, or train. She will arrive by bike — a journey she began in Washington just a few days after receiving her master’s degree.
Showing that science is accessible
Spokes is an MIT-based nonprofit that each year sends students on a transcontinental bike ride. Aluru worked for months with seven fellow MIT students on logistics and planning. Since setting out, the team has bonded over their love of memes and cycling-themed nicknames: Hank “Handlebar Hank” Stennes, Clelia “Climbing Cleo” Lacarriere, Varsha “Vroom Vroom Varsha” Sandadi, Rebecca “Railtrail Rebecca” Lizarde, JD “JDerailleur Hanger” Hagood, Sophia “Speedy Sophia” Wang, Amulya “Aero Amulya” Aluru, and Jessica “Joyride Jess” Xu. The support minivan, carrying food, luggage, and occasionally injured or sick cyclists, even earned its own nickname: “Chrissy”, short for Chrysler Pacifica.
“I really wanted to do something to challenge myself, but not in a strictly academic sense,” Aluru says of her decision to join the team and bike more than 3,000 miles this summer.
The Spokes team is not biking across the country solely to accomplish such a feat. Throughout their journey, they’ll be offering a variety of science demonstrations, including making concrete with Rice Krispies, demonstrating the physics of sound, using 3D printers, and, in Aluru’s case, extracting DNA from strawberries.
“We’re going to be in a lot of really different learning environments,” she says. “I hope to demonstrate that science can be accessible, even if you don’t have a lab at your disposal.”
The team was beset with challenges from the first day they started their journey. Aluru’s first day on the road involved driving to every bike shop and REI store in the D.C. metro area to purchase bike computers for navigation because the ones the team had already purchased would only display maps of Europe.
Aluru says she’s excited to see parts of the country she’s never visited before, and experience the terrain under her own power — except for breaks when it’s her turn to drive Chrissy.
Rolling with the ups and downs
Aluru was only a few weeks into her first Undergraduate Research Opportunities Program project in the late professor Angelika Amon’s lab when the Covid-19 pandemic hit, quickly transforming her wet lab project into a computational one. David Waterman, her postdoc mentor in the Amon Lab, was trained as a biologist, not a computational scientist. Luckily, Aluru had just taken two computer science classes.
“I was able to have a big hand in formulating my project and bouncing ideas off of him,” she recalls. “That helped me think about scientific questions, which I was able to apply when I came back to campus and started doing wet lab research again.”
When Aluru returned to campus, she began work in the Page Lab at the Whitehead Institute for Biomedical Research. She continued working there for the rest of her time at MIT, first as an undergraduate student and then as an MEng student.
The Page Lab’s work primarily concerns sex differences and how those differences play out in genetics, development, and disease — and the Department of Electronic Engineering and Computer Science, which oversees the MEng program, allows students to pursue computational projects across disciplines, no matter the department.
For her MEng work, Aluru looked at sex differences in human height, a continuation of a paper that the Page Lab published in 2019. Height is an easily observable human trait and, from previous research, is known to be sex-biased across at least five species. Genes that have sex-biased expression patterns, or expression patterns that are higher or lower in males compared to females, may play a role in establishing or maintaining these sex differences. Through statistical genetics, Aluru replicated the findings of the earlier paper and expanded them using newly published datasets.
“Amulya has had an amazing journey in our department,” says David Page, professor of biology and core member of the Whitehead Institute. “There is simply no stopping her insatiable curiosity and zest for life.”
Working with the lab as a graduate student came with more day-to-day responsibility and independence than when she was an undergrad.
“It was a shift I quite appreciated,” Aluru says. “At times it was challenging, but I think it was a good challenge: learning how to structure my research on my own, while still getting a lot of support from lab members and my PI [principal investigator].”
As Aluru looks to the future, she admits she’s not exactly sure what she’ll study — but when she reaches the West Coast, she knows she’s not leaving what she’s built through MIT far behind.
“There’s going to be a small MIT community even there — a lot of my friends are in San Francisco, and a few people I know are also going to be at Berkeley,” she says. “I have formed a community at MIT that I know will support me in all my future endeavors.”