Category: BSG-MSRP-Bio Student

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

Understanding the Role of PARPs and UBF1 in Building Ribosomes

Noah Daly | Department of Biology
September 25, 2024

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

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

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

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

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

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

Expanding Experiences While Narrowing Focus

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

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

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

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

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

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

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

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

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

The Unsolved Mysteries of UBF1

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BSG-MSRP-Bio student profile: Yeongseo Son, Spranger Lab

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.

When Yeongseo Son was initially invited to join the Spranger Lab as part of the Bernard S. and Sophie G. Gould MIT Research Program in Biology, she thought the email was spam. Having grown up in the South for most of her life, she had never pictured herself 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.”

Vexing Viruses

In the lab of Stefani Spranger, Associate Professor in the Department of Biology and Intramural Faculty of the Koch Institute for Integrative Cancer Research, Son was first tasked with a seemingly simple second project: growing a new strain of influenza to infect mice that had recently recovered from another strain. 

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.”

Yeongseo Son and Professor Spranger in the lab at the Koch Institute. Photo credit: Mandana Sassanfar.

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.

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

Fascination with regeneration led to summer program at MIT

Cryille Teforlack spent the summer investigating eye regeneration in flatworms as part of the BSG-MSRP-Bio program.

Lillian Eden | Department of Biology
September 15, 2023

Cyrille Teforlack first stumbled across the work of MIT Professor of Biology Peter Reddien on YouTube while Teforlack was taking a cell biology class at Bethune-Cookman University, where he is now a rising senior. Teforlack became fascinated by Reddien’s work on regeneration in planarians, freshwater flatworms. 

“That was how I figured out what kind of science I was interested in. I remember watching the video over and over,” Teforlack recalls. “I was like, ‘I have to figure out where this guy works.'”

The answer was, of course, at the Whitehead Institute, where Reddien is a Core Member and Associate Director. Teforlack spent the summer working in Reddien’s lab as part of the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio). The program offers students the opportunity to work on cutting-edge research that isn’t available at their home institutions. 

Teforlack showed a small sampling of regenerated eye traits at the 2023 BSG-MSRP-Bio poster session at the beginning of August

During the summer, Teforlack was working on eye regeneration and how different proteins and secreted factors affect the planarian’s cartoon-like crossed eyes. To understand the underlying requirements for regeneration, Teforlack used a technique called RNA interface (RNAi) to silence genes and see how it affected the planarian’s morphology when they regenerated. 

The phenotypes Teforlack saw—he had a list of more than 100 candidate genes to work with—ranged from barely noticeable to strikingly defective. He studied regeneration by slicing off the head of the worm to see how the head regenerated and removing the eyes from the intact head to see how just that organ regrew. 

“The eye has some connections to the brain and the rest of the body,” Teforlack explains. “But when you cut off their head, there’s no brain—but they can still regrow everything. It’s a no-brainer.”

However, some gene changes proved fatal or didn’t result in regeneration—the flatworms died and melted away. Teforlack didn’t realize that at first, however. There was one instance early in the program when he went to feed some worms—and was shocked to find they were missing. 

“It was a really scary day for me in the lab,” Teforlack jokes. “I lost 12 worms, somehow. But I remember feeding them yesterday. How do you lose worms?” 

Other phenotypes were more successful—showing atypical structures in the regenerated head or eyes. The optic cup of the eye regenerated in the wrong shape, for example, or separated in the middle as it regenerated. 

Teforlack has been surprised by how much is still unknown about planarian regeneration. For example, a particular gene is expressed when the worm needs to regenerate wounded tissue on the half of the body facing the head, as opposed to the tail; it is unclear, however, how the planarian body detects which side the wound is on. . 

“Even though it’s basic science, it’s still so intricate, and there’s so many little things that can build up to culminate in a bigger question,” Teforlack says. 

Teforlack became known as “the worm guy” among his fellow students.

“Having a cool organism to talk about makes talking about it more exciting for myself, and for everyone else that’s listening,” he says. “This is something I never thought I would be a part of. It feels really great to be at a cutting-edge place doing really cool research.” 

In addition to hands-on lab work, MSRP-Bio students often meet to discuss their work and do activities together. Teforlack says the program created plenty of opportunities to find community in his cohort, from arts and crafts to dodgeball.

The program also offers professional development activities like presentations from faculty including with the undergraduate and graduate officers Adam Martin and Mary Gehring to answer questions about applying for graduate school. Teforlack says he also found that faculty, despite their busy schedules, are always willing to take time out of their day for a chat.

“It’s been cool to meet all these different people and see the diversity of science that goes on and how many of them collaborate together on a variety of different projects,” Teforlack says. “This experience has helped me think like a scientist and value my own opinions. Being in an environment where your ideas are accepted, and you can learn from these scientists, has been really exciting.”  

Teforlack worked closely with HHMI staff scientist Lucila Simone and graduate student Bryanna Canales. Canales herself participated in the program. As an MSRP-Bio student, Canales worked on metastasis in zebrafish in the lab of Daniel K. Ludwig Professor for Cancer Research, and Koch Institute Intramural Faculty Richard O. Hynes. 

Canales says explaining her work to her peers during her time in MSRP-Bio was invaluable because it was more like teaching—she had to explain things in simple terms and found she was not the only one who sometimes struggled to do that. 

Cyrille Teforlack, left, discussing his project on flatworm eye regeneration with attendees of the 2023 BSG-MSRP-Bio Poster session, including Department of Biology Head Amy Keating.

“The program made me feel more comfortable talking to people that I could learn from,” Canales recalls. “The MSRP-Bio experience humanized the institution and the people here. Everyone here is really smart, but going through the process with the students in my cohort, it feels like less of a big deal if you don’t know something.” 

Canales says she’s seen Teforlack’s confidence grow this summer, taking the initiative and staying one step ahead instead of asking what he should be doing. 

“It’s been nice to know that I can do science by myself—more or less—and still feel accomplished and know that everything I’m doing is the correct step, and if it’s not, I know how to troubleshoot things,” Teforlack says.

Teforlack’s work culminated in a poster session in August for MSRP-Bio students, where he showed some of the defective phenotypes he was characterizing and a short movie of the planarians eating the RNAi delivery system: liver. 

“Cyrille showed a captivating movie of the small worms eating liver laced with double-stranded RNA that can downregulate specific genes,” says MIT Biology Department Head Amy Keating. “He also had beautiful images of the resulting phenotypes, which included disrupted optic cup structure. I always learn something new at the MSRP poster session!”

Long term, Teforlack plans to pursue a PhD in stem cell biology, and he says the program has reinforced that desire. 

“It’s been cool to be around so many scientists,” Teforlack says. “Ten weeks isn’t enough time for anyone to learn anything perfectly. I’m excited to grow as a researcher.” 

Although the MSRP-Bio program has come to a close for 2023, Teforlack’s time isn’t done in Reddien’s lab: he will return to continue his work in 2024. 

“The MSRP program is a great opportunity for students to directly immerse in research here at MIT and to learn new concepts and methods,” Reddien says. “Cyrille was a terrific student and contributed a lot over the summer. I look forward to seeing his next steps with research into regeneration.”