Meet the CMIT 2024 Rasmussen Fellows
Q&A with Alyssa Haynes Mitchell and Daniel Pascal
The Rasmussen Fellowships were established by Neil and Anna Rasmussen in 2023 to support microbiome research and training at MIT through the Center for Microbiome Informatics and Therapeutics. Each year, two graduate students are awarded a Rasmussen Fellowship: one in the department of Biological Engineering (BE) and one in the Institute for Medical Engineering and Science (IMES). These fellowships contribute to the Center’s goals of supporting excellence in microbiome research at MIT, advancing the next generation of microbiome innovators, and merging the unique expertise and resources of BE and IMES.
Alyssa Haynes Mitchell and Daniel Pascal, the Center’s inaugural Neil and Anna Rasmussen Fellowship recipients, discuss their research, interest in the microbiome, and key challenges in the field.
Alyssa Haynes Mitchell
Alyssa Haynes Mitchell holds a B.A. and M.S. in Biology from Boston University. She is a third-year graduate student, pursuing her PhD in Microbiology in the Lieberman Lab (IMES), where she uses an evolutionary lens to investigate the engraftment, stability, and person-specific adaptation of commensal bacteria in both the gut and vaginal microbiomes. Alyssa is keen to apply her expertise to develop therapeutic interventions for microbiome-related disorders after graduation and cares deeply about advancing health equity in resource-limited settings.
What drew you to study the microbiome?
Microbiome research really brings together a lot of my interests. Human health has always been a core motivator – initially I was considering a career as a physician — but I also really enjoy working with microbes, as well as the computational side of research and being able to draw conclusions from extensive, complex data. Part of my interest also stems from personal experience: my sister has Crohn’s disease and one of the things that really struck me about her experience was how helpless patients with IBD [inflammatory bowel diseases] can feel, because there are so many unanswered questions. IBD treatments, and IBD itself, still often seem like a “black box”, and I think that can really leave patients feeling on their own.
For a long time, I felt like these two driving interests – helping patients vs. doing research – were an “either/or” decision: I could be a doctor, or I could be a scientist. I come from a blue-collar family, and I think that one of the key hurdles that first-generation students face is not knowing all the opportunities and options that are available to them. That uncertainty changed part-way through my undergraduate studies. I had a pivotal moment when I was preparing a journal club for my lab and read a paper about the development of a gut-on-a-chip system. The potential to culture fecal biopsies to create personalized treatments for microbiome-related disorders captivated me. It was the first time I realized that I could bring together my passions for research and for helping patients, and that the skills I was developing in my fundamental microbiology work could lead to tangible improvements for people like my sister. This realization helped shape my passion for translational research and motivation to be on the leading edge of personalized medicine and therapeutic interventions via microbiome modulation.
What are the challenges or opportunities in microbiome science that excite you the most, and how do these intersect with your work?
I’m very excited about potential for probiotics — I think this is a space where microbiome research can have a major impact. It’s also a really tricky space because it’s hard to know how an organism will act in a specific person, both in the short and long term. I see engraftment — i.e., how or whether a given bacterium will colonize an individual — and whether it will persist long-term, as key challenges, which I’m addressing in my research. I’m culturing and whole-genome sequencing specific bacterial strains from clinical samples (from both the gut and vaginal microbiomes). Using these genomes, I’m identifying genomic loci that are under selection as well as pathways that are undergoing common vs. person-specific evolution. The degree to which evolution is person-specific can provide insights into how individual host environments shape microbial function and adaptation, which is highly relevant to the design of successful probiotics.
Beyond the science, I think another key challenge for the field will be to consider cultures and communities outside the United States, as well as within the U.S., but outside affluent cities. Right now, funding resources and the regulatory landscape don’t track with the global burden of disease. That’s not specific to microbiome research, but I think one interesting thing about microbiome-based treatments is the fact that on the one hand, microbiome research is incredibly complex, expensive, and requires advanced technology — but on the other hand, there are cultures that have been using microbiome-based treatments for centuries (like fecal “teas”). I think there’s a lot of opportunity to learn from those different perspectives and cultures. I’m excited to tap into CMIT’s global network to connect, collaborate, or otherwise serve microbiome researchers and communities in under-resourced settings.
Your research on person-specific bacterial adaptation in the gut is a collaboration with a local biotech company. What are some of the benefits you’ve experienced by collaborating with industry?
Working with industry has allowed me to jump right into the microbiology and computational analysis aspects of my project, which has been incredibly helpful. Through this collaboration, I’ve been able to access existing clinical samples, along with sequencing data and extensive patient metadata. The fact that the company had already figured out a lot of the initial microbiology obstacles — e.g., growth media and conditions – also helped accelerate my research.
Overall, working with industry has helped me appreciate microbiome science in its clinical and economic contexts. I’ve enjoyed thinking about the science from an industry perspective and have gained valuable insights on the unique challenges of producing a microbiome-based therapeutic, from specific drug development strategies and clinical trial design to the costs and challenges of manufacturing a live biotherapeutic. In fact, I plan to pursue a career in industry, to apply my expertise to develop and improve microbiome treatments.
Any fun facts or last thoughts?
Fun fact: Including in-laws, I have twenty-four siblings — so a considerable amount of my free time is spent on FaceTime!
More seriously, I’m grateful that there is philanthropic support for microbiome research from generous donors. We’ve seen biotech funding take a bit of a hit in the current climate, so it’s encouraging to be supported by donors who believe in the tremendous potential of this challenging field.
Daniel Pascal
Daniel Pascal holds a B.S. in Biomedical Engineering from Tufts University. He is a fourth-year graduate student, pursuing a PhD in Biological Engineering in the Voigt Lab. Daniel is using synthetic biology to develop a new treatment for bacteria-associated gastrointestinal infections, engineering a commercially available probiotic to deliver antimicrobial peptides that target pathogens in the gut but leave the native microbiome intact. Daniel is excited to use synthetic biology to redesign microbes for additional therapeutic applications in the future.
What drew you to study the microbiome?
From a scientific perspective, I’m fascinated by the microbiome’s inherent complexity and radical importance in all facets of life. The microbiome impacts a vast number of diseases, for better or for worse, with effects ranging from mild to life-threatening. It’s amazing to me that these microscopic organisms have such dynamic range: that they can, on the one hand, wreak such havoc and, on the other, bring such health benefits. I think this presents an exciting opportunity for research crucial to improving human health. Furthermore, directly manipulating the behaviors and composition of microbes within the human microbiome provides an additional and very attractive avenue towards therapeutic development beyond typical pharmaceutical approaches that focus on abiotic, small-molecule drugs. Synthetic biology provides a powerful toolbox to redesign microbes for therapeutic purposes – i.e., engineering them to act as a “living pharmacy” — and this wealth of potential clinical treatments is largely untapped.
From a personal perspective, I knew when I came to MIT that I wanted to work in a field that would improve public health. One experience that influenced me was volunteering with Hospital de la Familia, where I served as a translator for physicians on a surgical mission to Guatemala. Seeing the number of people who came in who couldn’t be helped because of how severe their conditions were, or because so little was known about them, really hit home for me the need for translational research that could have a meaningful impact on people’s lives. As one example, I think microbiome-based approaches are a critical tool to address antimicrobial resistance, which is a huge and growing problem worldwide, but poses special challenges in low and middle-income countries.
What are the challenges or opportunities in microbiome science that excite you the most, and how do these intersect with your work?
So much has been learned about the microbiome over the past decade, but translating all that amazing foundational science into therapies is still a huge challenge. Doing an experiment in vitro vs. getting an intervention to work in vivo is night and day — it’s like doing a physics problem on a test vs. landing Rover on Mars. I think synthetic biology is playing a key role in overcoming those translational barriers, as we develop better genetic tools and circuits, and figure out how to minimize metabolic burden on the engineered microorganism.
For example, in my research, I’m engineering a probiotic to deliver microcins [antimicrobial peptides] targeting the pathogens that cause traveler’s diarrhea (TD). This targeted approach offers an attractive alternative to broad-spectrum antibiotics, which disrupt the native microbiome — though when a living organism is producing the microcins it incurs a large burden. Nonetheless, so far we’ve successfully built a genetic circuit that produces two microcins at physiologically relevant doses, and shown that it reduces five different TD pathogens in mixed microbial communities. Our preliminary data from rat and pig-intestine models shows that the microcins specifically target twelve different pathogens while not impacting the native gut microbiome.
What advice would you give to new students who are interested in studying the microbiome but aren’t sure where to start?
Maximize your exposure to different research groups, both in your rotations but also in informal settings. Develop your network. Talk to as many professors and lab members as you can — there are so many different approaches out there, so many different avenues available to you. I rotated in an immunology lab, a mucus lab, and a DNA origami lab before coming to the Voigt lab. Most importantly, don’t be afraid to step outside your comfort zone. I had never cultured a living cell before joining the Voigt lab — I was more focused on developing biomaterials and devices as an undergraduate. You don’t know what you don’t know — so don’t be afraid to try something entirely new!
Any fun facts or last thoughts?
Two weeks before I started my rotation on traveler’s diarrhea in the Voigt lab, I went to Tulum, Mexico, drank some tap water, and it’s probably not difficult to guess what happened next. The silver lining, if you can call it that, of that otherwise harrowing experience was that it reinforced my fascination for the molecular processes in the gut microbiome and got me thinking about how we could develop targeted treatments for pathogens in the human digestive system.