Author: Lillian Eden

Summer research opportunity can be a springboard to advanced studies

The paths three graduate students forged to the same Picower Institute lab illustrate the value of participating in the MIT Summer Research Program in Biology and Neuroscience.

David Orenstein | The Picower Institute for Learning and Memory
August 16, 2023

Doctoral studies at MIT aren’t a calling for everyone, but they can be for anyone who has had opportunities to discover that science and technology research is their passion and to build the experience and skills to succeed. For Taylor Baum, Josefina Correa Menéndez and Karla Alejandra Montejo, three graduate students in just one lab of The Picower Institute for Learning and Memory, a pivotal opportunity came via the MIT Summer Research Program in Biology and Neuroscience (MSRP BIO). When a student finds MSRP-BIO, it helps them find their future in research.

In the program undergraduate STEM majors from outside MIT spend the summer doing full-time research in the Departments of Biology or Brain and Cognitive Sciences (BCS), or the Center for Brains, Minds and Machines (CBMM). They gain lab skills, mentoring, preparation for graduate school and connections that might last a lifetime. Over the last two decades, a total of 215 students from under-represented minority groups, who are from economically-disadvantaged backgrounds, first-generation or non-traditional college students, or students with disabilities have participated in research in BCS or CBMM labs.

Like Baum, Correa Menéndez, and Montejo, the vast majority go on to pursue graduate studies, said Diversity & Outreach Coordinator Mandana Sassanfar, who runs the program. For instance, among 91 students who have worked in Picower Institute labs, 81 have completed their undergraduate studies. Of those, 46 enrolled in PhD programs at MIT or other schools such as Cornell, Yale, Stanford, Princeton, and the University of California System. Another 12 have gone to medical school, another 7 are in MD/PhD programs and 3 have earned master’s degrees. The rest are studying as post-baccalaureates or went straight into the workforce after earning their bachelor’s.

After participating in the program, Baum, Correa Menéndez, and Montejo each became graduate students in the research group of Emery N. Brown, Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering in The Picower Institute and the Institute for Medical Engineering and Science. The lab combines statistical, computational and experimental neuroscience methods to study how general anesthesia affects the central nervous system to ultimately improve patient care and advance understanding of the brain. Brown said the students have each been doing “off the scale” work, in keeping with the excellence he’s seen from MSRP BIO students over the years.

“I think MSRP is fantastic. Mandana does this amazing job of getting students who are quite talented to come to MIT to realize that they can move their game to the next level. They have the capacity to do it. They just need the opportunities,” Brown said. “These students live up to the expectations that you have of them. And now as graduate students, they’re taking on hard problems and they’re solving them.”

Paths to PhD studies 

Pursuing a PhD is hardly a given. Many young students have never considered graduate school or specific fields of study like neuroscience or electrical engineering. But Sassanfar engages students across the country to introduce them to the opportunity MSRP BIO provides to gain exposure, experience and mentoring in advanced fields. Every fall, after the program’s students have returned to their undergraduate institutions, she visits schools in places as far flung as Florida, Maryland, Puerto Rico, and Texas and goes to conferences for diverse science communities such as ABRCMS and SACNAS to spread the word.

When Baum first connected with the program in 2017, she was finding her way at Penn State University. She had been majoring in biology and music composition but had just switched the latter to engineering following a conversation over coffee exposing her to brain-computer interfacing technology,  in which detecting of brain signals of people with full-body paralysis could improve their quality of life by enabling control of computers or wheelchairs. Baum became enthusiastic about the potential to build similar systems, but as a new engineering student, she struggled to find summer internships and research opportunities.

“I got rejected from every single progam except the MIT Center for Brains Minds and Machines MSRP,” she recalled with a chuckle.

Baum thrived in MSRP BIO, working in Brown’s lab for three successive summers. At each stage, she said, she gained more research skills, experience and independence. When she graduated, she was sure she wanted to go to graduate school and applied to four of her dream schools. She accepted MIT’s offer to join the Department of Electrical Engineering and Computer Science, where she is co-advised by faculty members there and by Brown. She is now working to develop a system grounded in cardiovascular physiology that can improve blood pressure management. A tool for practicing anesthesiologists, the system automates the dosing of drugs to maintain a patient’s blood pressure at safe levels in the operating room or intensive care unit.

More than that, Baum not only is leading an organization advancing STEM education in Puerto Rico, but also is helping to mentor a current MSRP BIO student in the Brown lab.

“MSRP definitely bonds everyone who has participated in it,” Baum said. “If I see anyone who I know participated in MSRP, we could have an immediate conversation. I know that most of us, if we needed help, we’d feel comfortable asking for help from someone from MSRP. With that shared experience, we have a sense of camaraderie, and community.”

In fact, a few years ago when a former MSRP BIO student named Karla Montejo was applying to MIT, Baum provided essential advice and feedback about the application process, Montejo said. Now as a graduate student, Montejo has become a mentor for the program in her own right, Sassanfar noted. For instance, Montejo serves on program alumni panels that advise new MSRP BIO students.

Montejo’s family immigrated to Miami from Cuba when she was a child. The magnet high school she attended was so new that students were encouraged to help establish the school’s programs. She forged a path into research.

“I didn’t even know what research was,” she said. “I wanted to be a doctor, and I thought maybe it would help me on my resume. I thought it would be kind of like shadowing, but no, it was really different. So I got really captured by research when I was in high school.”

Despite continuing to pursue research in college at Florida International University, Montejo didn’t get into graduate school on her first attempt because she hadn’t yet learned how to focus her application. But Sassanfar had visited FIU to recruit students and through that relationship Montejo had already gone through MIT’s related Quantitative Methods Workshop (QMW). So Montejo enrolled in MSRP BIO, working in the CBMM-affiliated lab of Gabriel Kreiman at Boston Children’s Hospital.

“I feel like Mandana really helped me out gave me a break, and the MSRP experience pretty much solidified that I really wanted to come to MIT,” Montejo said.

In the QMW, Montejo learned she really liked computational neuroscience and in Kreiman’s lab she got to try her hand at computational modeling of the cognition involved in making perceptual sense of complex scenes. Montejo realized she wanted to work on more biologically based neuroscience problems. When the summer ended, because she was off the normal graduate school cycle for now, she found a two-year postbaccalaurate program at Mayo Clinic studying the role a brain cell type called astrocytes might have in the Parkinson’s Disease treatment deep brain stimulation.

When it came time to re-apply to graduate schools (with the help of Baum and others in the BCS Application Assistance Program) Montejo applied to MIT and got in, joining the Brown lab. Now she’s working on modeling the role of  metabolic processes in the changing of brain rhythms under anesthesia,  , taking advantage of how general anesthesia predictably changes brain states. The effects anesthetic drugs have on cell metabolism and the way that ultimately affects levels of consciousness reveals important aspects of how metabolism affects brain circuits and systems. Earlier this month, for instance, Montejo co-led a paper the lab published in The Proceedings of the National Academy of Sciences detailing the neuroscience of a patient’s transition into an especially deep state of unconsciousness called “burst suppression.”

A signature of the Brown lab’s work is rigorous statistical analysis and methods, for instance to discern brain arousals states from EEG measures of brain rhythms. A PhD candidate in MIT’s Interdisciplinary Doctoral Program in Statistics, Correa Menéndez is advancing the use of Bayesian hierarchical models for neural data analysis. These statistical models offer a principled way of pooling information across datasets. One of her models can help scientists better understand the way neurons can “spike” with electrical activity when the brain is presented with a stimulus. The other’s power is in discerning critical features such as arousal states of the brain under general anesthesia from electrophysiological recordings.

Though she now works with complex equations and computations as a PhD candidate in Neuroscience and Statistics, Correa Menéndez was mostly interested in music art as a high school student at Academia María Reina in San Juan and then architecture in college at the University of Puerto Rico, Río Piedras campus. It was discussions at the intersection of epistemology and art during an art theory class that inspired Correa Menéndez to switch her major to biology and to take computer science classes, too.

When Sassanfar visited Puerto Rico in 2017, a computer science professor (Dr. Patricia Ordóñez) suggested that Correa Menéndez apply for a chance to attend the QMW. She did and that led her to also participate in MSRP BIO in the lab of Sherman Fairchild Professor Matt Wilson (a faculty member in BCS, CBMM and The Picower Institute). She joined in the lab’s studies of how spatial memories are represented in the hippocampus and how the brain makes use of those memories to help understand the world around it. With mentoring from then-postdoc Carmen Varela (now a faculty member at Florida State University), the experience not only exposed her to neuroscience, but also, she gained skills and experience with lab experiments, building research tools, and conducting statistical analyses. She ended up working in the Wilson lab as a research scholar for a year and began her graduate studies in September 2018.

Classes she took with Brown as a research scholar inspired her to join his lab as a graduate student.

“Taking the classes with Emery and also doing experiments made me aware of the role of statistics in the scientific process: from the interpretation of results to the analysis and the design of experiments,” she said. “More often than not, in science, statistics becomes this sort of afterthought—this ‘annoying’ thing that people need to do to get their paper published. But statistics as a field is actually a lot more than that. It’s a way of thinking about data. Particularly, Bayesian modeling provides a principled inference framework for combining prior knowledge into a hypothesis that you can test with data.”

To be sure, no one starts out with such inspiration about scientific scholarship, but MSRP BIO helps students find that passion for research and the paths it opens up.

Meet a Whitehead Postdoc: Pavana Rotti
Greta Friar | Whitehead Institute
August 4, 2023
3 Questions: Daniel Lew on what we can learn from yeast about cell movement, communication, and shape

New Professor of Biology Daniel Lew uses budding yeast to address fundamental questions in cell biology

Lillian Eden | Department of Biology
August 3, 2023

Sipping a beer on a warm summer evening, one might not consider that humans and yeast have been inextricably linked for thousands of years; winemaking, baking, and brewing all depend on budding yeast. Outside of baking and fermentation, researchers also use Saccharomyces cerevisiae, classified as a fungus, to study fundamental questions of cell biology.

Budding yeast gets its name from the way it multiplies. A daughter cell forms first as a swelling, protruding growth on the mother cell. The daughter cell projects further and further from the mother cell until it detaches as an independent yeast cell.

How do cells decide on a front and back? How do cells decode concentration gradients of chemical signals to orient in useful directions, or sense and navigate around physical obstacles? New Department of Biology faculty member Daniel “Danny” Lew uses the model yeast S. cerevisiae, and a non-model yeast with an unusual pattern of cell division, to explore these questions.

Q: Why is it useful to study yeast, and how do you approach the questions you hope to answer?

A: Humans and yeast are descended from a common ancestor, and some molecular mechanisms developed by that ancestor have been around for so long that yeast and mammals often use the same mechanisms. Many cells develop a front and migrate or grow in a particular direction, like the axons in our nervous system, using similar molecular mechanisms to those of yeast cells orienting growth towards the bud.

When I started my lab, I was working on cell cycle control, but I’ve always been interested in morphogenesis and the cell biology of how cells change shape and decide to do different things with different parts of themselves. Those mechanisms turn out to be conserved between yeast and humans.

But some things are very different about fungal and animal cells. One of the differences is the cell wall and what fungal cells have to do to deal with the fact that they have a cell wall.

Fungi are inflated by turgor pressure, which pushes their membranes against the rigid cell wall. This means they’ll die if there is any hole in the cell wall, which would be expected to happen often as cells remodel the wall in order to grow. We’re interested in understanding how fungi sense when any weak spots appear in the wall and repair them before those weak spots become dangerous.

Yeast cells, like most fungi, also mate by fusing with a partner. To succeed, they must do the most dangerous thing in the fungal lifecycle: get rid of the cell wall at the point of contact to allow fusion. That means they must be precise about where and when they remove the wall. We’re fascinated to understand how they know it is safe to remove the wall there, and nowhere else.

We take an interdisciplinary approach. We’ve used genetics, biochemistry, cell biology, and computational biology to try and solve problems in the past. There’s a natural progression: observation and genetic approaches tend to be the first line of attack when you know nothing about how something works. As you learn more, you need biochemical approaches and, eventually, computational approaches to understand exactly what mechanism you’re looking at.

I’m also passionate about mentoring, and I love working with trainees and getting them fascinated by the same problems that fascinate me. I’m looking to work with curious trainees who love addressing fundamental problems.

Q: How does yeast decide to orient a certain way—towards a mating partner, for example?

A: We are still working on questions of how cells analyze the surrounding environment to pick a direction. Yeast cells have receptors that sense pheromones that a mating partner releases. What is amazing about that is that these cells are incredibly small, and pheromones are released by several potential partners in the neighborhood. That means yeast cells must interpret a very confusing landscape of pheromone concentrations. It’s not apparent how they manage to orient accurately toward a single partner.

That got me interested in related questions. Suppose the cell is oriented toward something that isn’t a mating partner. The cell seems to recognize that there’s an obstacle in the way, and it can change direction to go around that obstacle. This is how fungi get so good at growing into things that look very solid, like wood, and some fungi can even penetrate Kevlar vests.

If they recognize an obstacle, they have to change directions and go around it. If they recognize a mating partner, they have to stick with that direction and allow the cell wall to get degraded. How do they know they’ve hit an obstacle? How do they know a mating partner is different from an obstacle? These are the questions we’d like to understand.

Q: For the last couple of years, you’ve also been studying a budding yeast that forms multiple buds when it reproduces instead of just one. How did you come across it, and what questions are you hoping to explore?

A: I spent several years trying to figure out why most yeasts make one bud and only one bud, which I think is related to the question of why migrating cells make one and only one front. We had what we thought was a persuasive answer to that, so seeing a yeast completely disobey that and make as many buds as it felt like was a shock, which got me intrigued.

We started working on it because my colleague,Amy Gladfelter, had sampled the waters around Woods Hole, Massachusetts. When she saw this specimen under a microscope, she immediately called me and said, “You have to look at this.”

A question we’re very intrigued by is if the cell makes five, seven, or 12 buds simultaneously, how do they divide the mother cell’s material and growth capacity five, seven, or 12 ways? It looks like all of the buds grow at the same rate and reach about the same size. One of our short-term goals is to check whether all the buds really get to exactly the same size or whether they are born unequal.

And we’re interested in more than just growth rate. What about organelles? Do you give each bud the same number of mitochondria, nuclei, peroxisomes, and vacuoles? That question will inevitably lead to follow-up questions. If each bud has the same number of mitochondria, how does the cell measure mitochondrial inheritance to do that? If they don’t have the same amount, then buds are each born with a different complement and ratio of organelles. What happens to buds if they have very different numbers of organelles?

As far as we can tell, every bud gets at least one nucleus. How the cell ensures that each bud gets a nucleus is a question we’d also very much like to understand.

We have molecular candidates because we know a lot about how model yeasts deliver nuclei, organelles, and growth materials from the mother to the single bud. We can mutate candidate genes and see if similar molecular pathways are involved in the multi-budding yeast and, if so, how they are working.

It turns out that this unconventional yeast has yet to be studied from the point of view of basic cell biology. The other thing that intrigues me is that it’s a poly-extremophile. This yeast can survive under many rather harsh conditions: it’s been isolated in Antarctica, from jet engines, from all kinds of plants, and of course from the ocean as well. An advantage of working with something so ubiquitous is we already know it’s not toxic to us under almost any circumstances. We come into contact with it all the time. If we learn enough about its cell biology to begin to manipulate it, then there are many potential applications, from human health to agriculture.

Whitehead Institute researchers receive an HHMI Gilliam Fellowship
Merrill Meadow | Whitehead Institute
July 31, 2023
Freeman Hrabowski encourages students to ‘Hold fast to dreams’ and take time for laughter

On MIT campus, Hrabowski led a lively and inspiring Q&A with students.

Lillian Eden | Department of Biology
July 20, 2023

A group of more than 50 — predominantly MSRP-Bio students and alums and current students from the Meyerhoff Scholars program and the University of Maryland, Baltimore County — recently had the pleasure of sitting down for an informal chat at MIT with distinguished educator, author, and mathematician Freeman Hrabowski. 

Hrabowski is widely credited for transforming UMBC into a world-renowned, innovative institution while serving as its president from 1992-2022. The educator also ushered in a generation of Black students to earn PhDs in science and engineering, co-founding the Meyerhoff Scholars Program at UMBC. Founded in 1988, the program has become a national model for increasing diversity in STEM.  Hrabowski was also a member of the President’s Advisory Commission on Educational Excellence for African Americans during the Obama administration. 

A crowd of more than 50 in a lecture hall with Freeman Hrabrowski standing in front of them.
Freeman Hrabowski led a call-and-response recitation of a mantra until everyone could participate flawlessly: “Your thoughts, they become your words. Your words, they become your actions. Your actions, they become your habits. Your habits, they become your character. Your character becomes your destiny.” Photo credit: Mandana Sassanfar.

Hrabowski began by quoting poet William Carlos Williams “It is difficult to get the news from poems yet men die miserable every day for lack of what is found there,” and leading a call-and-response recitation of the poem Dreams by Langston Hughes as well as a mantra encouraging students to use their words, actions, and habits to shape their character and their destiny. Afterward, the students asked Hrabowski about his life and experiences. 

“The audience of high-achieving students asked terrific, insightful questions reflecting their contemplation of their own paths,” says Biology Department head Amy Keating. “When students spoke up, Hrabowski engaged with them, and their ideas and perspectives were welcomed and respected. By the end of his time with them, almost everyone had their hand up and wanted to contribute to the lively discussion.”

Tobias Coombs, a Meyerhoff Scholars program alumnus and current graduate student in the Spranger Lab, says the event was an example of “classic Freeman Hrabowski”: Hrabowski injected the crowd with excitement and energy. Coombs also remarked that Hrabowski, named by Time as one of the world’s most influential people in 2012, acknowledged to the group that he’s shy, something Hrabowski is still pushing himself to overcome.

“He makes a point of being this down-to-earth person that you feel you can talk to about real issues and have real conversations with,” Coombs says. “He genuinely wants to motivate you to think science and math are cool.”

Before taking questions from the students in attendance, Hrabowski posed one to them: what do you think it takes to be successful in research in STEM? Among the responses were passion, curiosity, and a supportive community. After each response, Hrabowski encouraged a round of applause for each student brave enough to stand and give an answer because “Everybody needs support.”

“The way that you think about yourselves, the language that you use, the way that you interact with each other, and the values that you hold, will be so important. You become like the things that you love,” Hrabowski says.

For his lifetime of accomplishments increasing diversity in STEM, the Howard Hughes Medical Institute recently announced a new program named after Hrabowski. The HHMI Freeman Hrabowski Scholars were selected for their potential to become leaders in their research fields and to foster diverse and inclusive lab environments. The inaugural class of 31 scholars includes MIT Biology faculty members Seychelle Vos, the Robert A. Swanson Career Development Professor of Life Sciences, and Hernandez Moura Silva, an assistant professor and Ragon Institute core member, as well as MIT Biology and Cheeseman lab alumna Kara McKinley, PhD ’16.

Group of 10 people standing in a line posing for a photo.
Hrabowski (5th from the right) was very excited to see UMBC alums as well as HHMI Freman Hrabowski Scholars Hernandez Moura Silva (3rd from the right) and Seychelle Vos (to the left of Hrabowski) at MIT. Photo credit: Mandana Sassanfar.

Vos and Moura Silva were among the faculty attending the event, and both say Hrabowski was an inspiring guest to have on campus.

“Dr. Hrabowski’s smile, energy, and words are a true force of nature,” Hernandez says. “His words of wisdom showed us that we can all make the impossible possible by bringing a positive attitude to build a strong, supportive, and diverse community. It was such an honor to have him here.”

Biology department undergraduate officer Adam Martin says he noticed the pride in Hrabowski’s eyes when Hrabowski discussed what his trainees and faculty in his programs have accomplished. Biology department graduate officer Mary Gehring said his visit made her remember why she wanted to be a professor: “to help others follow their passions to their full potential.” 

Hrabowski reflected on many topics, including the recent Supreme Court ruling on affirmative action. He pointed out that this was not the first time the Supreme Court had ruled on a racially conscious initiative, namely the 1995 decision that a UMBC scholarship program was unconstitutional. To continue the Meyerhoff Scholars Program, which was affected by the Supreme Court decision at the time, Hrabowski worked with Maryland’s Attorney General, found language and methods to encourage broad participation of diverse individuals, and focused on what the program was trying to achieve.

“My message to everyone was ‘where there’s a will, there’s a way.’ If the institution wants to continue to build diversity and broader participation, we can do it,” he says. “What we’re

working to achieve in the Meyerhoff program and in the Freeman Hrabowski Scholars program is to have everybody included.”

Hrabowski also offered advice on more everyday challenges: good students, himself included, can focus too much, forgetting to make time for other important aspects of their lives. He has learned to make time for Tai Chi, acupuncture, and getting his steps in; he encouraged the students similarly to take time for themselves outside work or school.

Six people standing in the Picower Institute for Learning and Memory, laughing.
Freeman Hrabowski (middle) chatting with MIT Biology faculty at MIT. Photo credit: Lillian Eden.

“When you can have fun and laugh, you’re a much better person. You can be a better thinker if you take care of yourself overall,” he says. “It’s the healthy person who can be most effective.”

As for being intimidated or nervous to talk to a superior, Hrabowski had the room roaring with laughter at his advice: “Just remember they go to the bathroom, too.”  

Keating noted that Hrabowski engaged with the audience with energy, compassion, and humor. 

She also observed, “No one can hide in Dr. Hrabowski’s classroom.”

“He put students front and center in his presentation, and his emphasis on the joys and importance of learning, knowledge, and achievement inspired us all to go back to the lab and classroom and be our best selves,” Keating says. “He acknowledged that paths in STEM demand much of us, and he encouraged students to have the discipline needed to stay the course while also taking care of themselves.”

It takes three to tango: transcription factors bind DNA, protein, and RNA
Greta Friar | Whitehead Institute
July 7, 2023

Transcription factors could be the Swiss Army knives of gene regulation; they are versatile proteins containing multiple specialized regions. On one end they have a region that can bind to DNA. On the other end they have a region that can bind to proteins. Transcription factors help to regulate gene expression—turning genes on or off and dialing up or down their level of activity—often in partnership with the proteins that they bind. They anchor themselves and their partner proteins to DNA at binding sites in genetic regulatory sequences, bringing together the components that are needed to make gene expression happen.

Transcription factors are a well-known family of proteins, but new research from Whitehead Institute Member Richard Young and colleagues shows that the picture we have had of them is incomplete. In a paper published in Molecular Cell on July 3, Young and postdocs Ozgur Oksuz and Jonathan Henninger reveal that along with DNA and protein, many transcription factors can also bind RNA. The researchers found that RNA binding keeps transcription factors near their DNA binding sites for longer, helping to fine tune gene expression. This rethinking of how transcription factors work may lead to a better understanding of gene regulation, and may provide new targets for RNA-based therapeutics.

“It’s as if, after carrying around a Swiss Army knife all your life for its blade and scissors, you suddenly realize that the odd, small piece in the back of the knife is a screwdriver,” Young says. “It’s been staring you in the face this whole time, and now that you finally see it, it becomes clear how many more uses there are for the knife than you had realized.”

How transcription factors’ RNA binding went overlooked

A few papers, including one from Young’s lab, had previously identified individual transcription factors as being able to bind RNA, but researchers thought that this was a quirk of the specific transcription factors. Instead, Young, Oksuz, Henninger and collaborators have shown that RNA-binding is in fact a common feature present in at least half of transcription factors.

“We show that RNA binding by transcription factors is a general phenomenon,” Oksuz says. “Individual examples in the past were thought to be exceptions to the rule. Other studies dismissed signs of RNA binding in transcription factors as an artifact—an accident of the experiment rather than a real finding. The clues have been there all along, but I think earlier work was so focused on the DNA and protein interactions that they didn’t consider RNA.”

The reason that researchers had not recognized transcription factors’ RNA binding region as such is because it is not a typical RNA binding domain. Typical RNA binding domains form stable structures that researchers can detect or predict with current technologies. Transcription factors do not contain such structures, and so standard searches for RNA binding domains had not identified them in transcription factors.

“We show that RNA binding by transcription factors is a general phenomenon,” Oksuz says.

Young, Oksuz and Henninger got their biggest clue that researchers might be overlooking something from the human immunodeficiency virus (HIV), which produces a transcription factor-like protein called Tat. Tat increases the transcription of HIV’s RNA genome by binding to the virus’ RNA and then recruiting cellular machinery to it. However, Tat does not contain a structured RNA binding site; instead, it binds RNA from a region called an arginine-rich motif (ARM) that is unstructured but has a high affinity for RNA. When the ARM binds to HIV RNA, the two molecules form a more stable structure together.

The researchers wondered if Tat might be more similar to human transcription factors than anyone had realized. They went through the list of transcription factors, and instead of looking for structured RNA binding domains, they looked for ARMs. They found them in abundance; the majority of human transcription factors contain an ARM-like region between their DNA and protein binding regions, and these sequences were conserved across animal species. Further testing confirmed that many transcription factors do in fact use their ARMs to bind RNA.

RNA binding fine tunes gene expression

Next, the researchers tested to see if RNA binding affected the transcription factors’ function. When transcription factors had their ARMs mutated so they couldn’t bind RNA, those transcription factors were less effective in finding their target sites, remaining at those sites and regulating genes. The mutations did not prevent transcription factors from functioning altogether, suggesting that RNA binding contributes to fine-tuning of gene regulation.

Further experiments confirmed the importance of RNA binding to transcription factor function. The researchers mutated the ARM of a transcription factor important to embryonic development, and found that this led to developmental defects in zebrafish. Additionally, they looked through a list of genetic mutations known to contribute to cancer and heritable diseases, and found that a number of these occur in the RNA binding regions of transcription factors. All of these findings point to RNA binding playing an important role in transcription factors’ regulation of gene expression.

They may also provide therapeutic opportunities. The transcription factors studied by the researchers were found to bind RNA molecules that are produced in the regulatory regions of the genome where the transcription factors bind DNA. This set of transcription factors includes factors that can increase or decrease gene expression. “With evidence that RNAs can tune gene expression through their interaction with positive and negative transcription factors,” says Henninger, “we can envision using existing RNA-based technologies to target RNA molecules, potentially increasing or decreasing expression of specific genes in disease settings.”

Notes

Ozgur Oksuz, Jonathan E. Henninger, Robert Warneford-Thomson, Ming M. Zheng, Hailey Erb, Adrienne Vancura, Kalon J. Overholt, Susana Wilson Hawken, Salman F. Banani, Richard Lauman, Lauren N. Reich, Anne L. Robertson, Nancy M. Hannett, Tong I. Lee, Leonard I. Zon, Roberto Bonasio, Richard A. Young. “Transcription factors interact with RNA to regulate genes.” Molecular Cell, July 3, 2023. https://doi.org/10.1016/j.molcel.2023.06.012.

Department of Biology opens its doors for Community College outreach

15 from Bunker Hill Community College visited campus as part of an outreach initiative to build stronger ties with local institutions that serve diverse, nontraditional learners.

Lillian Eden | Department of Biology
July 6, 2023

Although many undergraduates may be home for the summer, the halls and labs of MIT are still teeming with activity. On a sunny Thursday in June, 15 students from Bunker Hill Community College (BHCC) got to peek behind the curtain of research at MIT. 

The Community College Partnership builds ties with two local community colleges that serve diverse, nontraditional students. The program was first conceived in 2020 as part of the biology department’s participation in #ShutDownSTEM, a day to consider equity and inclusion for marginalized communities and to educate and take action against injustice. 

The visit is part of a larger effort to encourage students to pursue research opportunities and careers in research at and beyond MIT; other initiatives include virtual career panels and workshops for students at BHCC and Roxbury Community College. In addition, two community college students perform research as part of MRSP-Bio each summer, thanks to funding from the Packard Foundation acquired by Ankur Jain, Assistant Professor of Biology and Core Member of the Whitehead Institute. 

BHCC students toured the MIT Cryo-EM facility with director Sarah Sterling. Photo Credit: Mandana Sassanfar

Sarah Sterling, Director of the Cryo-EM facility, loves giving tours because students ask such great questions, and the BHCC students were no exception: they were curious and inquisitive at every stop of their tour. Sterling explained that she chose her position, in part, because she enjoys “facilitating science”—helping researchers use cutting-edge equipment to find answers to their questions. 

The students also visited labs in Building 68, Whitehead Institute, and the Picower Institute for Learning and Memory. 

 Reddien Lab postdoc Thomas Cooke described exploring mechanisms of regeneration in planarians, and Professor Laurie Boyer described the core questions underlying her research on heart development. 

“The process of forming tissues and organs works sufficiently well that we’re all here, and we’re all relatively healthy,” Boyer says. “To me, that is remarkable.” 

What isn’t well understood, she explains, is how faulty regulation can lead to disease and congenital malformations, and research using model systems can provide answers. For example, creating a model system in a dish can lead to a better understanding of the formation of circuits and molecular players. That, in turn, can lead to therapies or early diagnosis. The lab also works on tools to visualize what is occurring inside cells because “seeing is believing.”

“As scientists, we are not only trying to plan the best experiments possible, but we are also trying to develop new tools that push the boundaries of what we can discover,” she says. “Keeping an eye on the big picture is important because you’re never studying a problem in isolation. You’re studying a biological mechanism that has implications for many different things.” 

It was “really eye-opening” to see what’s happening in some of the labs, according to BHCC student Robinson Le. Le is a dancer turned Biology major but had only ever come to campus for breakdancing practice—a skill they showed off to cheering BHCC students during lunch. 

BHCC students with Department of Biology Faculty Laurie Boyer. Photo Credit: Mandana Sassanfar

Badara Mbengue, another BHCC student, was excited to learn “what everyday life is like in the department.” 

“It makes me very happy to see how much this has grown and continues to grow,” says Sheena Vasquez, PhD ‘23, who helped spearhead the initiative. 

BHCC alums at MIT also showed students around the labs they are working in and shared their experiences at MIT, including as MSRP-Bio students, Quantitative Methods Workshop students, and as an undergraduate transfer student. 

Libby Dunphy, a professor at BHCC, helped arrange the visit. She says the trip was an excellent opportunity for her students, who don’t get much exposure to real research.

“Seeing actual researchers, seeing that they’re real people, and that they’re nice, can help students imagine themselves in this place,” Dunphy says. “The Bunker Hill motto is ‘imagine the possibilities.’ And it’s cheesy, but we’re imagining the possibilities here.” 

Boyer also offered advice for pursuing research at this stage in the students’ careers. 

“The opportunities are unlimited, and so many people would be happy to support you—but sometimes, you have to ask,” Boyer advises. “Stay ambitious. You should be so proud of yourselves for embarking on this journey.”