CSB Seminar: Dr. Dalia Barsyte, Principal Investigator, Structural Genomics Consortium

Host:  Prof. David Lovejoy <david.lovejoy@utoronto.ca>

Epigenetic regulators are broad protein families that enzymatically modify histones/proteins or bind to the modified histones/substrates. These methyl-, acetyl-transferases, bromodomain proteins or demethylases play a role in gene transcription, chromatin condensation, cell division, DNA repair, telomere maintenance and retroviral silencing. To study the function of the epigenetic regulators, we generated specific small molecule inhibitors that allow chemical modulation of the system without perturbing the protein complexes. Such chemical targeting enabled the investigation into the function of G9a and GLP in ES cell specific retroviral silencing, SUV420 enzyme role in homologous DNA repair and PRMT5 enzyme driven methylation of protein substrates involved in splicing and cellular signaling. PRMT5 methyltransferase is essential for leukemia stem cell survival and interaction with the stroma cells that facilitates the expression of the stem cell markers. Inhibition of PRMT5 down-regulates the stem cell markers and leukemia cell survival. The protective role of the stroma-leukemia cell interaction and the niche-based micro-environment modulation by epigenetic regulators is being investigated.

Video Conferencing at UTM (DV 3131) & UTSc (MW229)