Category: Feature

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.

From open education learners to MIT coders

MIT Digital Learning Lab’s high school interns gain professional experience working on the backend of open online MITx courses. The program emerged after Mary Ellen Wiltrout, PhD '09, digital learning scientist at MIT Open Learning, connected with the executive director and founder of Empowr, a nonprofit that serves low-income communities by creating a school-to-career pipeline through software development skills.

Katherine Ouellette | MIT Open Learning
August 26, 2024

Switching programming languages is not as simple as switching word processors. Yet high schooler Thomas Esayas quickly adapted from Swift to Python during his 2023 internship with the MIT Digital Learning Lab, a joint program between MIT Open Learning and the Institute’s academic departments. One year later, Esayas returns to the Institute for a second internship and as a new undergraduate student.

“I felt thoroughly challenged and learned a lot of new skills,” says Esayas.

Through this remote opportunity, interns gain real-world coding experience and practice professional skills by collaborating on MIT’s open online courses. The four interns from Digital Learning Lab’s 2023 and 2024 cohorts also participate in Empowr, a four-year program for low-income high school students that teaches in-demand software development skills and helps them secure paid internships.

The Digital Learning Lab program emerged after Mary Ellen Wiltrout PhD ’09, digital learning scientist at MIT Open Learning, connected with Adrian Devezin, executive director and founder of Empowr, at a conference about making education more accessible and equitable.

“It was affirming to have someone else see what Empowr is trying to do,” says Devezin about the organization’s goal to strengthen the school-to-career pipeline. “Being able to collaborate was beautiful for me, and more importantly, to the students.”

Building technical skills and self-confidence

The Digital Learning Lab internship empowers students to build confidence in their technical abilities, career skills, and the college application process. Interns assist the lab’s digital learning scientists with their work developing and maintaining online MITx courses at Open Learning across multiple academic areas.

“I found myself always busy with something interesting to work on,” says Esayas.

The interactive open education resources that Esayas produced last summer are now being used in live courses. He also helped find and fix bugs on the platform that hosts the MITx courses.

The internship’s flexible design allows projects to be adapted based on the student’s personal progress and interests.

“The students became co-creators of their educational experiences,” says Wiltrout, noting this is beneficial from a pedagogical standpoint.

Devezin adds, “I definitely saw a big improvement in their problem-solving abilities. Having to switch their mindset to a new language, work in new frameworks, and work on teams solving real problems enhanced their ability to adapt to new situations.”

The students’ also strengthened their professional repertoire in areas such as collaboration, communication, and project management. The 2023 cohort, Devezin says, developed the initiative to help other students and take on leadership roles.

Now that Esayas has completed his 2024 internship, he says, “I’m glad that I got to collaborate with more people and work on more projects. Overall, I’m very happy I was able to return.”

two people smiling, standing in front of a colorful wall.
Adrian Devezin, executive director and founder of Empowr (left), and Mary Ellen Wiltrout, digital learning scientist at MIT Open Learning (right), presented their takeaways from the first year of the MIT Digital Learning Lab internship at the 2024 Open edX conference. Photo courtesy of Empowr.

Learning from both sides

Learning occurred for both students and educators alike. Wiltrout says that the Digital Learning Lab values the opportunity to see the interns’ growth day-to-day and week-to-week, since digital learning scientists rarely follow the trajectory of individual learners who are using the course materials they create. Having instant feedback informs how they can adjust their teaching approaches for various problems.

The positive impact of the Digital Learning Lab internship’s hands-on learning experiences has made Devezin rethink the way he teaches class moving forward, and “the problems I want them to be solving,” he says.

Now, Devezin tries to emulate the real-world experience of working on a project for his Empowr students. Instead of assigning coding exercises where he provides the exact methods to solve the problems, he started asking students to determine the correct approach on their own.

The fact that Wiltrout and Devezin are open to adapting their teaching methods based on student feedback is indicative of a key factor to the internship’s success — active participation in students’ growth. It was mutually beneficial for the students and the educators to have determined stakeholders at both Digital Learning Lab and Empowr.

“A lot of dedicated educators understand that there’s a lot of inequities in education, and we need to come together to solve them,” Devezin says.

The Digital Learning Lab internship shows how open source learning materials can make educational and professional opportunities more accessible. The 2024 cohort has been able to increase their annual household income by an average of 75%, a recent Empowr report revealed. Wiltrout says that the two new Empowr students seem more confident with coding and showed enthusiasm and dedication to their tasks as they also consider colleges.

Wiltrout and Devezin presented their takeaways from the internship’s first year at the 2024 Open edX conference.

“I think it’s important to try making sure that more people are aware of tools and resources that are out there,” Wiltrout says. “Then giving people opportunities where they may not have otherwise had that chance.”

Now, Devezin is thinking about how Empowr students can come full circle with their relationship to open educational materials. He’s asking, “How can I help my students contribute to the open source world to give back to others?”

Lessons in building the future of teaching and learning

Nine shifts in pedagogical and learning approaches since the global pandemic.

Yvonne Ng | MIT Open Learning
August 7, 2024

The Covid-19 pandemic created radical shifts in approaches to teaching and learning. And while the social, emotional, and mental toll of the pandemic has diminished greatly over the last four years, residual challenges still remain for students and educators. Mary Ellen Wiltrout PhD ’09, director of online and blended learning initiatives, lecturer, and digital learning scientist in Biology at MIT, has identified these shifts in her article, “How to build the future of teaching and learning while growing from the changes and challenges of 2020–21.”

In her article, published in 2022 in Advances in Online Education: A Peer-Reviewed Journal, Wiltrout hypothesized on the lasting impacts of the 2020–2021 events on teaching and learning organized across seven themes: course logistics, tools, activities and assessment for learning, student services and programs, work culture, attitudes, and relationships. Now in 2024 at MIT, Wiltrout can see the positive changes continuing and progressing in these areas:

Flexibility: During the pandemic, instructors were more flexible about coursework requirements, scheduling, grading structure, and expanded the number and types of assignments beyond summative exams. Some enacted policies enabling partial flexibility such as dropping the lowest score on assignments or allowing for late submissions. Now, with student support services approval, instructors remain open to working with students in need of flexibility.

Online learning: Residential colleges relying on completely in-person education now incorporate more blended learning and online courses for students interested in that option. Hybrid instruction and online assignments continue to be part of the curriculum.

Technology: The most valuable functions of the learning management system are the organization of course events and materials and the integration of the multitude of learning tools in one place with one login (for example, web conferencing, discussion forum, grading, video, and calendar). As a result of reducing barriers, more tools like online conferencing, polling, and tablet drawing software to teach, are being used by a larger percentage of teaching staff and students.

Reducing unconscious bias: Grading exams and assignments through an online tool increased the efficiency and consistency of grading with rubrics for every question. And the ability to anonymize submissions in the grading process helps reduce unconscious biases, while students also gain transparency from the rubrics to learn from mistakes and trust the process.

Rethinking in-person sessions: More conversations emerged on how to take advantage of in-person interactions to prioritize activities of value in that mode for learning and work. Instructors and students intentionally kept online approaches that enriched the experience as students returned to campuses. Some digital components enhance student learning, mental well-being, equity, or inclusion and could be as easy as providing a course chat channel for peer-to-peer and peer-to-staff conversations during synchronous sessions. Some instructors maintained more creative, open-ended assignments and online exam policies that seemed experimental during 2020.

Demand for student support services: The effects of the pandemic combined with normalizing taking care of mental health resulted in the sustained high demand for student support services. Institutions continue to invest more in the staffing of these services and programs, such as peer mentoring programs that result in positive academic and attitudinal gains for students. Instructors are generally more aware of how to positively influence students to seek help with simple actions, like speaking in a warm tone and intentionally including a statement about student services.

Belonging and inclusion: Racial and social injustices are being addressed more openly than ever before. Many institutions are recognizing the value and importance of diversity, equity, and inclusion in their students and staff and have invested in funding and training for their community to shift their culture in a positive way. At the course level, instructors have the training and resources available to learn how to become more inclusive teachers (through free resources such as massive open online courses or internal efforts) and have the student and institution pressure to do so.

Mentoring: With the help of online tools and technology, students, educators, and staff are able to foster and create meaningful internship programs. Mentoring in these online programs with students in disparate locations around the world continues to take place and have a positive impact for students and any research that may be part of a program.

Collaborations: Although possible before, more researchers see collaborations across states or countries as less of a hurdle, especially with the everyday use of tools like Zoom. Instructors enhance authentic experiences for students by bringing outside experts into the classroom virtually for discussion — a method that was not used often before the pandemic.

Wiltrout concludes that many opportunities for widespread maintenance of practices that worked well and benefited students during the pandemic can and should continue to persist and grow into the future. Instructors also expanded and improved their curricula and pedagogical approaches to nurture a more inclusive and engaging course for their students and themselves.

“The lasting impacts of the pandemic include profound lessons on what best served both learners and educators,” Wiltrout says. “It’s heartening to see changes and adjustments to pedagogy, student services and programs, attitudes, and relationships that continue to benefit everyone. If these new effective ways endure and grow, then a better future of education for students, staff, and instructors is possible.”

Improving biology education here, there, and everywhere

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.

Transforming Veterans’ Lives, One Kidney Transplant at a Time

When Reynold I. Lopez-Soler, SB ’94, saw his first kidney transplant, during his medical residency, he found his life’s work.

Kathryn M. O'Neill | MIT Technology Review
September 6, 2024

When Reynold I. Lopez-Soler ’94 saw his first kidney transplant, during his medical residency, he found his life’s work.

“It’s such a magical and incredible thing that you can do this,” says Lopez-Soler, director of the renal transplant program at the Edward Hines Jr. Veterans Affairs Hospital outside Chicago. “You’re watching this organ that was taken out [of the donor], practically lifeless and inert, and through the expertise of surgery it comes to life and becomes pink; it starts to make urine.”

About 100,000 people in the United States are currently waiting for a kidney transplant; on average, they will wait five to seven years. Lopez-Soler is expanding access to this care for veterans.

Kidney transplants are life-changing, he says, not only because kidney disease can make people very sick, but because the main treatment—dialysis, which does some of the kidney’s job outside the body—is so demanding that many patients can’t work or even travel. “Getting a kidney transplant not only fixes the problem, but fixes their lives going forward,” he says. “There is this substantial transformation.”

Growing up in Puerto Rico, Lopez-Soler always expected to become a surgeon (his father is a surgical oncologist). During high school, he discovered the MIT Introduction to Technology, Engineering, and Science (MITES) program, spent a summer on campus, and fell in love with the Institute. “MIT was an incredibly inclusive place,” he says. “Whatever you did, you were welcome. I’ve brought that acceptance with me in my ethos in how I deal with people.”

After majoring in biology at MIT (with a minor in Spanish literature), Lopez-Soler earned his MD and PhD from Northwestern University and completed his surgical residency at Yale New Haven Hospital. Then he practiced in Virginia and New York, where he was director of research at Albany Medical Center.

In 2019, Lopez-Soler was tapped to establish the VA transplant program at Hines, and in its first year, it completed 36 kidney transplants. Last year, the center did 105. He now chairs the Department of Veterans Affairs Transplant Surgery Surgical Advisory Board, which helps develop transplant policies and procedures for the whole VA system.

The grandson of a brigadier general, Lopez-Soler is proud to serve veterans. “I was lucky enough to fall in love with the job because of the people we treat,” he says. “It exposed me to these amazing veterans who have done so much for this country.”

This story also appears in the September/October issue of MIT Alumni News magazine, published by MIT Technology Review.

Photo illustration by Mary Zyskowski; image of Reynold I. Lopez-Soler courtesy of Lopez-Soler.

Growing to greatness: Professor Mary Gehring on plant epigenetics and becoming an HHMI Investigator

From the intricacies of plant reproduction to genome-wide analyses, Gehring’s lab delves deep into the epigenetic mechanisms shaping plant biology.

Jayashabari Shankar and Alex Tang | The Tech
September 5, 2024

Dr. Mary Gehring is a professor of biology at MIT and a core member of the Whitehead Institute for Biomedical Research. Her research focuses on how epigenetic mechanisms like DNA methylation influence gene regulation during plant reproduction and seed development in the model organism Arabidopsis thaliana. In the classroom, she teaches genetics (7.03), a required course for biology and biological engineering majors.

With her recent appointment as an Howard Hughes Medical Institute (HHMI) investigator, Gehring joins an elite legion of HHMI investigators at the Institute. New cohorts of investigators are only announced once every three years, and they receive $11 million in funding over a seven year term (which can be renewed). Three other MIT faculty received HHMI appointments this year: Gene-Wei Li, associate professor of biology, and brain and cognitive sciences professors Mehrdad Jazayeri and Steven Flavell.

Here, she shares her lab’s research, journey into plant biology, and what she values in undergraduate researchers.

TT: What does your lab conduct research in, and how has being named an HHMI investigator changed your plans, if at all?

My lab focuses on plant biology, particularly on how epigenetic mechanisms like DNA methylation affect gene regulation in plants, especially during reproduction and seed development. We mostly work with Arabidopsis thaliana, a model plant, but we’re also exploring other plant systems.

A typical day in the lab can vary, but it often starts with checking on our plants in the greenhouse. Depending on the day, we might pollinate plants for genetic crosses or genotyping them by isolating DNA and performing PCR. We’re particularly focused on understanding gene expression within seeds: we isolate different seed tissues, sort nuclei based on their properties, and then perform RNA sequencing. We also do a lot of chromatin profiling, histone modifications and DNA methylation analyses across the genome. Since much of our work is genome-wide, bioinformatics plays a big role in our research, with a significant amount of time spent on analyzing data.

It’s still sinking in, but being named an HHMI investigator certainly provides a new level of freedom. It allows us to pursue ideas without the constraints of specific grant funding, which is incredibly liberating. We’re considering expanding our research into new areas beyond epigenetics, like genome structure and chromosome dosage changes, while sticking with plant biology. This recognition has encouraged us to think bigger and explore new directions in our work.

TT: How far back do these interests extend for you?

My interest in plant biology started during my undergraduate years. I majored in biology and was eager to get involved in research. My real fascination with plants began when a new professor, with a background in plant biology, came to my school. I took her course on plant growth and development, which I found incredibly exciting. I was drawn to how plants communicate within their tissues and with each other. This led me to work on a research project for two years, culminating in a senior thesis on root development. After college, I took a year off to work in environmental consulting before heading to graduate school in Plant Biology at UC Berkeley.

TT: What perspectives and characteristics do you appreciate in undergraduate researchers?

Whether it’s undergraduates or postdocs, I value curiosity and dedication. For undergraduates, especially those in UROPs, it’s crucial that they are genuinely interested in the research and willing to ask questions when they don’t understand something. Balancing research with coursework and extracurriculars at MIT is challenging, so I also look for students who can manage their time well. It’s about being curious, dedicated, and communicative.

I hope there are students at MIT who are excited about plant research. It’s a vital area of biology, especially with the growing focus on climate change. While there isn’t a large presence of plant biology at MIT yet, I’m hopeful that it will expand in the coming years, and I’d love to see more students getting involved in this important field.

2024 Angelika Amon Young Scientist award winners announced

The Koch Institute at MIT is pleased to announce the winners of the 2024 Angelika Amon Young Scientist Award, Anna Uzonyi and Lukas Teoman Henneberg.

Koch Institute
September 3, 2024

The Koch Institute at MIT is pleased to announce the winners of the 2024 Angelika Amon Young Scientist Award, Anna Uzonyi and Lukas Teoman Henneberg.

The prize was established in 2021 to recognize graduate students in the life sciences or biomedical research from institutions outside the United States who embody Dr. Amon’s infectious enthusiasm for discovery science.

Both of this year’s winners work to unravel the fundamental biology of chromatin, the densely structured complex of DNA, RNA, and proteins that makes up a cell’s genetic material.

Uzonyi is pursuing her PhD at the Weizmann Institute of Science in Israel under the supervision of Schraga Schwartz and Yonatan Stelzer. In her thesis, Uzonyi focuses on deciphering the principles of RNA editing code via large-scale systematic probing.

Henneberg is a doctoral candidate in the Department of Molecular Machines and Signaling, at the Max Planck Institute of Biochemistry in Germany, works under the supervision of Professor Brenda Schulman and Professor Matthias Mann. For his research project, he probes active ubiquitin E3 ligase networks within cells. He works on the development of probes targeting active ubiquitin E3 ligases within cells and utilizing them in mass spectrometry-based workflows to explore the response of these ligase networks to cellular signaling pathways and therapeutics.

This fall, Anna Uzonyi and Lukas Teoman Henneberg, will visit the Koch Institute. The MIT community and Amon Lab alumni are invited to attend their scientific presentations on Thursday, November 14 at 2:00 p.m. in the Luria Auditorium, followed by a 3:30 p.m. reception in the KI Galleries.

Uzonyi will present on “Inosine and m6A: Deciphering the deposition and function of adenosine modifications” and Henneberg will present on “Capturing active cellular destroyers: Probing dynamic ubiquitin E3 ligase networks.“

No detail too small

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.”

RNA processing and gene expression governing

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 students are 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.”

Back to the basics of gene regulation

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 students are 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.”