Shriya Sankaran Rose Hills
Investigating DNA Methylation Machinery via Single Molecule Tracking
The cell is regulated by complex interactions between proteins, RNA, and DNA. Epigenetic processes are one class of these interactions, where DNA or chromatin is modified to control gene expression, repair, and organization. Disruption of DNA methylation, in particular, is linked to cancer and developmental disorders, making it critical to understand how DNA methylation is maintained over time to preserve cellular homeostasis.
DNA methyltransferase 1 (DNMT1) plays a central role in maintaining DNA methylation across cell divisions. It acts in concert with the enzyme UHRF1 to add methyl groups to unmethylated CpG sites. However, the in vivo dynamics of UHRF1–DNMT1 interactions with DNA are not well understood. To address this, I use single-molecule tracking (SMT) with an oblique line scan (OLS) microscope to track fluorescently labeled DNMT1 and UHRF1 over time. This approach enables quantification of their interactions at high spatial and temporal resolution, including whether they are freely diffusing or chromatin-bound, and how DNMT1 kinetics change when UHRF1 function is disrupted. Ultimately, this work will clarify the mechanism by which DNMT1 maintains DNA methylation.
Message To Sponsor
I'm deeply grateful for the opportunity to devote myself to this project, and to develop myself as a researcher. As a bioengineering and computer science student, I'm excited about this project that fuses state-of-the-art imaging technologies, computational analysis, and fundamental biology. DNA methylation is such a fundamental cellular process that plays a role in every stage of development and regulation, and science stands to gain from a thorough understanding of its mechanisms.