Shedding Light on the Mysteries of Protein Folding
Owen Hurlbut Lesk '25
Biochemistry and Molecular Biology
Commonwealth Honors College
Boxborough, MA
What drew you to this field of study?
I have been interested in biology since I was very young, and have felt drawn to proteins in particular since I learned more about them in high school. My dad works in a similar field, and he has always inspired me to ask questions and think in-depth about protein science. Prior to matriculating at UMass Amherst, I had the opportunity to work full time for six months in a lab, where I studied the protein that is responsible for cystic fibrosis, CFTR. This experience really pushed me to apply my prior knowledge about proteins and biological systems and helped me grow as a scientist. Consequently, I was encouraged to study biochemistry and molecular biology at UMass Amherst and applied to the Gierasch Lab, a biophysics lab on campus that studies protein folding and the mechanisms of molecular chaperones.
How do you conduct your research?
I am studying a critical step in the folding of secreted proteins during their passage through the endoplasmic reticulum (ER) in human cells. One third of the proteins produced in human cells move through the ER, and it is in this cellular compartment where these proteins must adopt their native folded states. Proteins that successfully fold within the ER are allowed to progress through the cell, but proteins that fail to fold within the ER are degraded and never reach their final destinations or serve their cellular roles. Protein folding within the ER is regulated by the key gatekeeper enzyme, which selectively moderates protein escape from the ER by only allowing proteins that have folded successfully to their native states to continue to their final destinations. However, the mechanism enabling the key gatekeeper to serve this critical role is yet unknown, and that is what my research seeks to elucidate.
Much of my research is performed in a wet lab environment. My research has also come to include analysis of computational models of the proteins that I work with, followed by application of these data to design experiments in the lab.
What do you see as the impact—or potential impact—of your work?
My research seeks to improve our understanding of protein folding in animals (including humans), plants, and other higher eukaryotes. This work may be relevant to diseases that involve secretory protein misfolding, including diabetes and serpinopathies such as alpha-1 antitrypsin deficiency. I hope my research will give me a unique perspective in the field, one that I can apply to explore further interesting questions in the future.
How does your faculty mentor support your research?
Dr. Lila M. Gierasch has always pushed me to take a step back and think about my research, rather than diving into an experiment without a proper plan. She has inspired me to pursue a career as an academic and to challenge my assumptions about any system that I am working with or thinking about. She has helped me become an independent scientist, but always supports my learning and has created an environment where I feel comfortable asking for help.
I am continuously driven by a desire to learn, and a research environment challenges my knowledge and inspires me to keep learning more material in greater depth.
What do you find most exciting about your research?
I am continuously driven by a desire to learn, and a research environment challenges my knowledge and inspires me to keep learning more material in greater depth. It is fun to ask questions and probe systems in rigorous and creative ways! I also like the idea that basic scientific research, like the study of protein/protein interactions and molecular chaperones, could one day help patients or the general public.
What are you most proud of?
I am proud to be part of a lab on campus. It has completely changed my experience as an undergraduate student and as a researcher, especially since my previous lab experience was at a pharmaceutical company. I am proud to work with my wonderful lab mates and collaborate with faculty and researchers in my field.
How has your research enhanced your overall educational experience at UMass?
Participating in research constantly challenges me to think about complex biological systems in the lab, and this experience has dramatically changed how I think in my classes. In several of my courses, we have discussed topics that relate directly to my research or my peers' research, and my previous experience with these topics has truly aided my learning in these classes. My research also has encouraged me to read scientific literature extensively, including papers from broad and disparate academic fields that have changed my approach to learning in general. Whenever I am faced with an interesting question, I turn to the existing literature first! I want to remain in academia in part because of my institutional journal access. My lab mates are incredibly supportive, and the lab also provides me with a unique space to study.
What are your plans for the future?
After I receive my bachelor's degree from UMass, I plan to pursue a graduate degree in a field that interests and inspires me, likely something related to protein folding. One day, I plan to become a professor as I enjoy teaching others, but also like the world of academic research.
Why would you recommend UMass to a friend?
I would recommend UMass to any friend who is interested in research in an academic setting. There are countless labs and other research opportunities on campus, and they could pursue questions in many uniquely interesting fields.