I chose CMDB because I have long been interested in the modularity of biological systems, the emergent properties that arise through the interaction of biomolecules, and their potential for rational design. I have been fortunate to be involved in scientific research since high school. My first project involved engineering an intrabody for the efficient degradation of misfolded Huntingtin, the culprit underlying Huntington’s disease. Ever since that time, I have been interested in better understanding the organizing principles of protein function so that we can elucidate the molecular mechanisms of disease and rationally manipulate biological systems at the cellular and organismal levels. When choosing a graduate program, I was interested in de novo protein design but given my interest in biological systems across scales, and having never worked in the field, I sought graduate programs that offered the opportunity to study protein design but also had labs which excelled in areas like cell biology and developmental biology. I remember, when I found the webpage for the CMDB program, its title seemed to be a little too good to be true given my interests. Upon examination of the pages for affiliated faculty and the curriculum, it became clear that this program offered everything I wanted.

The way in which amino acid sequences encode conformational change remains poorly understood. In my thesis research, I am working to understand the relationship between sequence and fold for a set of 8,000 proteins using novel high-throughput experimental techniques. The proteins in this space all possess at least 77% sequence identity but differ in fold, with some having been found to be metamorphic, meaning they populate two distinct folds under equilibrium conditions. By characterizing the conformational ensembles of all 8,000 proteins, I hope to gain insights into the sequence signatures associated with conformational heterogeneity, such that we might better understand and predict conformational change based on an amino acid sequence. I find high-throughput experimentation to be particularly exciting because it allows us to put our models of protein behavior and function to the test and get a better sense of how well they generalize to evolutionarily and functionally distinct proteins.

I chose to be co-mentored by Vince Hilser and Doug Barrick during my thesis research and my project has only been made possible due to their unique interests and areas of expertise. The choice to be co-mentored was initially questioned by many people, but the opportunity to learn from two exceptional biophysical chemists while designing a research project that combines expertise from both labs has proven invaluable to my growth as a scientist. I also love being part of two labs because it provides me with a greater number of colleagues with whom I can brainstorm and troubleshoot. I found that everyone sees problems differently and the solutions that I find when I ask for input from multiple peers are almost always better than those I would have come up with on my own.