Meet the Lab

My research training prior to starting my PhD was focused on molecular dynamics simulations of cardiac proteins. However, upon starting graduate school, I was introduced to the field of epigenetics and soon enough, I knew I was hooked! This was where my wet lab journey began.

Epigenetics is the study of changes in gene expression that do not involve changes to the DNA sequence itself. In particular, I found it remarkable that the epigenetic mark of DNA methylation played such a critical role in regulating a cell’s gene expression. This pathway is quite fragile, though, and cases of abnormal methylation patterns can lead to cancer proliferation. In such cases, methylated DNA ‘readers’ become upregulated and facilitate propagation of these abnormal methylation patterns resulting in tumorigenesis. We aim to solve the crystal structures of such proteins and to better understand the role of allostery in how they recognize their binding targets. With such structural and mechanistic insights, we can then computationally design optimized inhibitors for cancer therapeutic application.

Remarkable for their diversity and specificity, RNA-protein interactions represent chemical communication between two of the major molecular players in the chemistry of life. As an undergraduate, I studied the biochemistry of such interactions involved in splicing. In the Bailey Lab, I hope to use a structural approach to probe the intricate networks of interactions involved in PAM recognition by various CRISPR systems, exploring the mechanistic basis of information transfer from PAM sequences to downstream events such as domain rearrangement and recruitment of other proteins. To do so, I will use Cryo-EM to solve structures of CRISPR-Cas complexes bound to various PAM sequences to explain  functional biochemistry observations, focusing first on the thermophilic Type I-B system from Thermotoga maritima.

I realized the importance of basic biochemical research during my three years working in health care after completing my undergraduate degree. I saw how treatments for cancer and other diseases often carry serious side effects, and this made me want to contribute to their improvement.

I’m interested in the protein-nucleic acid interactions that lie at the foundation of all cellular processes. This, along with the novelty and utility of CRISPR biology, motivated me to join the Bailey lab as an ScM student in 2019.

As a master’s student, I studied the effects of target mutations in Type I CRISPR systems. During this time, I also developed a strong interest in structural biology and how proteins change their shape to bind and modify DNA.

As a PhD student, I will use a combination of biochemistry and cryo-electron microscopy to study the conformational rearrangements CRISPR-associated proteins undergo when they bind and cleave their targets.

I have always had a passion for cancer research, and I find the different approaches for developing cancer therapeutics fascinating, from drug development to the exploration of drug delivery methods. As an undergraduate, I worked in a biophysics lab that focused on quantifying membrane-ligand interactions and researching alternative drug carriers for medical applications. This research deepened my passion for therapeutic research, and I knew I wanted to continue exploring the field.

My interest in the Bailey lab stems from proteins that associate with abnormal DNA methylation patterns. Such aberrations in DNA methylation are found in most cancers. Currently I am working on solving the crystal structure of proteins that bind these DNA regions. Based on their structure, I can see how these proteins bind their targets, which will give the structural and mechanistic insight needed for cancer therapeutic drug design.

Before becoming an ScM student in the BMB Department, I developed an interest in basic science research at a small liberal arts college in Indiana through a project to synthesize a D-amino acid antibiotic. This project deepened my curiosity about the mechanisms bacteria have evolved to protect themselves from antibiotics, other bacteria, and even viruses. My interest in the Bailey lab sprung from my fascination with adaptive immune systems in bacteria. Currently, my goal is to use cryo-EM to understand the structure of the Thermatoga maritima Type III-B CRISPR complex, with and without a bound RNA target.

As an undergraduate, I was intrigued with the complexity of microorganisms and what their biology could teach us about fundamental biochemical mechanisms. Specifically, bacteria and phages have been my workplace throughout my career to study nucleoprotein complexes and the intimate interactions between proteins and DNA/RNA. While in graduate school, my dissertation focused on the repair of DNA mismatches and frameshifts utilizing purified components of the E. coli methyl-directed mismatch repair pathway. These studies revealed interesting ideas of how proteins can adapt to specifically bind and recognize seemingly diverse DNA targets.

As a post-doctoral fellow, my focus switched to the biochemical mechanisms of DNA replication initiation in the E. coli bacteriophage Lambda. During this stage of my career I was fascinated with how nucleoprotein complexes harness the free energy of DNA supercoiling to drive the unwinding of duplex DNA.

Currently I have taken my interest in nucleoprotein complexes to a new level, the atomic level. Utilizing single-particle cryo-electron microscopy, we are working to determine the 3D structure of various CRISPR complexes bound to their DNA or RNA substrates.