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Targeting the Regulatory Genome – The When, Where, and Why of Gene Transcription

Dr. Ian Tobias, University of Toronto – candidate for the Black/Indigenous faculty position in Biomedical Sciences will be giving a Research Talk on Monday June 19th at 1p in Room 3708 ECLA

Targeting the Regulatory Genome – The When, Where, and Why of Gene Transcription

Abstract:

Development unfolds from early embryonic cells containing species-specific genetic information. Distinct cell types supporting specialized tissue functions are primarily formed by tissue-specific gene expression changes that occur at developmentally restricted times. Recent functional genomic efforts suggest that some several hundred thousand non-protein coding DNA sequences scattered throughout mammalian genomes can regulate gene transcription, including transcriptional enhancers and insulators. Regulatory DNA orchestrates cell type-specific gene expression by serving as binding sites for transcription factors. There is, however, little mechanistic understanding of how these interactions control development and cell fate stability. Determining how mutations in transcription factor binding sites can disrupt gene regulatory programs and lead to phenotypic variation, including disease risk in human, domestic and wild animals, is of significant interest to One Health and precision medicine approaches. In this talk, I will share my post-doctoral work combining flexible genome editing tools with state-of-the-art genome-wide approaches which clarifies how a novel group of enhancers safeguard neural progenitor cell phenotype by controlling the expression of the transcription factor SRY box 2 (Sox2). Drawing on my expertise in regulatory genomics and mammalian stem cell biology, I am interested in deciphering the regulatory programs that shape development and the genetic basis of disease susceptibility in mammalian systems, including human, canine, and mouse. My research group aims to initially focus on (i) the evolution and function of neurodevelopmental gene regulation and (ii) the role of regulatory DNA sequence variation directly impacting stem cell biology and disease susceptibility.