The Power of Structural Biology

Sagar Gupta, COL ’24, Bakersfield, CA

This summer, I continued working in the molecular immunology lab I joined in my freshman year. My experience working in Dr. Nikolaos Sgourakis’s lab at the Children’s Hospital of Philadelphia has been incredibly fulfilling as I was able to apply the skills I have learned throughout the academic year towards the analysis of a promising therapeutic.

At the beginning of the summer, I gave a presentation at the monthly floor meeting of the Center for Computational and Genomic Medicine. Here, I detailed my findings on the structural classification of the class I major histocompatibility complex (MHC-I). This protein is encoded by the most polymorphic region of our genome. Nonetheless, its general structure is relatively conserved. Due to its essential role in the adaptive immune system, the MHC-I protein has been the focus of numerous computational modeling efforts. My work provides a scaffold which researchers can utilize to develop accurate structural predictions.

Next, I was given the opportunity to be involved in a project with one of my PI’s close collaborators, Dr. John Maris. Following the experimental structural determination of a key therapeutic, I was tasked with analyzing this structure to guide further experimental studies. I identified a set of strong interactions which were proven to be significant following experimental validation with surface plasma resonance (SPR) spectroscopy. Furthermore, I curated a set of similar structures using existing data in the Protein Data Bank (PDB) and compared our structure to characterize this therapeutic in the context of other known proteins. These findings will help guide further protein engineering efforts which aim to optimize similar therapeutics. I created publication-quality images and animations and presented these findings at Dr. Maris’s lab meeting along with another member of the Sgourakis lab.

I was fascinated to learn the power that a single structure can have in driving scientific discovery. Due to a generous grant from Career Services, I was able to pursue this opportunity and not concern myself with financial issues. My experience in Dr. Sgourakis’s lab has solidified my intention to pursue a career which blends structural biology and therapeutic development via an MD-PhD dual degree.

This is part of a series of posts by recipients of the 2022 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.

By Career Services
Career Services