The Institute of Environmental Health Sciences, the Center for Urban Responses to Environmental Stressors and the Department of Pharmacology at Wayne State University are pleased to invite the campus community to a hybrid seminar with guest speaker, Dr. Joshua Heyza, postdoctoral fellow at Michigan State University. Dr. Heyza will present, "Single-molecule imaging of DNA repair in living cells." The seminar will be held at the Integrative Biosciences Center and virtually via Zoom. The Zoom link will be emailed to registrants prior to April 25th. 

Abstract:

DNA double-strand breaks (DSBs) pose harmful threats to genome integrity. Therefore, defining mechanisms underlying DSB repair will enhance our understanding of how defects in these pathways contribute to human disease and could lead to the discovery of new approaches for therapeutic intervention. As a result of the sheer complexity of the DNA damage response and the various cellular DNA repair pathways, there are large gaps in our understanding of the molecular mechanisms underlying DNA repair in human cells. Methodological advances in live cell single-molecule imaging over the last decade now allow researchers to directly observe and analyze the dynamics of DNA repair proteins in living cells with high spatiotemporal resolution. Live cell single-molecule imaging combined with single-particle tracking can provide direct insight into the biochemical reactions that control DNA repair and has the power to identify previously unobservable processes in living cells. To that end, we established a panel of HaloTagged DNA damage response factors in U2OS cells using CRISPR-Cas9 which enables concentration-dependent protein labeling by fluorescent HaloTag ligands. Using these cell lines, we systematically analyzed total cellular protein abundance, measured recruitment kinetics to laser-induced DNA damage sites, and defined their diffusion dynamics and chromatin binding characteristics by live cell single-molecule imaging which has revealed new insights into the molecular mechanisms underpinning DNA repair in human cells. Altogether, our studies demonstrate the utility of single-molecule imaging to provide mechanistic insights into DNA repair, which will serve as a powerful resource for characterizing the biophysical and biochemical properties of DNA repair factors in living cells. 

Biography:

Dr. Joshua Heyza is a postdoctoral fellow at Michigan State University. He received his PhD in Cancer Biology from the Wayne State University School of Medicine in 2019. His research uses innovative genome-editing and live-cell imaging approaches to define molecular mechanisms that control DNA double-strand break repair, which plays an essential role in maintaining genomic integrity. Dr. Heyza's research is supported by a K99/R00 award from NIGMS.

We hope you are able to join us for this interesting seminar!