Surabhi Chowdhary, Ph.D.
B.S. Biotechnology, Panjab University, 2007
M.S. Biotechnology, Panjab University, 2009
Ph.D. Biochemistry and Molecular Biology, LSU Health Sciences Center-Shreveport, 2018
Three-dimensional chromatin organization is critical for proper regulation of gene expression, yet the extent to which genomic structure is altered following exposure of cells to stress remains largely unexplored. The overarching goal of my project is to investigate changes in the conformation and spatial organization of the yeast genome in response to acute thermal stress (heat shock).
The heat shock response in all eukaryotes, yeast to human, is largely regulated at the transcriptional level. Cells adapt to stress-induced proteotoxic conditions by activating an evolutionarily conserved sequence-specific transcriptional activator, Heat Shock Factor 1 (Hsf1). In the yeast Saccharomyces cerevisiae, our lab has shown that Hsf1 drives the basal and heat shock-inducible expression of 50 genes encoding molecular chaperones, co-chaperones and other cytoprotective proteins (Heat Shock Proteins; HSPs) essential to cell survival. Using a technique termed chromosome conformation capture (3C), my work has revealed that genes under the regulation of Hsf1 undergo dramatic transformations in chromatin structure upon their activation, including the formation of loops between their promoter and terminator regions and of physical contacts between regulatory and coding region sites (a phenomenon that we term “crumpling”). Even more striking, HSP genes dispersed throughout the genome engage in frequent physical interactions with each other and coalesce into transcriptionally active foci in response to thermal stress. Notably, heat shock-induced genes under regulation of alternative transcription factors (Msn2/Msn4) do not appear to coalesce, nor do constitutively expressed, highly transcribed genes. Therefore, my work suggests that Hsf1-regulated genes exhibit distinct, possibly unique, properties. My current efforts are directed towards defining the constellation of genes that coalesce into gene clusters using a state-of-the-art genome-wide technique termed ChIA-PET (Chromatin Interaction Analysis by Paired-End Tagging). In addition to providing unprecedented insights into the heat shock-remodeled interactome, my work in collaboration with others in lab will address the important question of how gene expression is affected as a consequence of reconfigured genome topology.
View Larger Image