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The focus of research in the Transcriptional Regulation Lab is regulation of gene expression by transcription factors during animal development. We primarily use the fruit fly Drosophila as a model system.
Animals, including humans, are made up of cells that differ dramatically in their size, shape, function, longevity and ability to keep dividing even though, with few exceptions, every cell contains the same genome. Different cell types express different combinations of genes from the common genome to gain their identity during embryonic development and to maintain their identity and integrity in later life. Thus, failure of correct gene regulation during foetal development usually results in death or severe congenital defects, and in adult life leads to disease including cancer.
Many families of transcription factors (including Hes, Runx, Nkx, LEF1/Tcf, Pax, Six, and Fox) that negatively regulate gene expression during animal development interact with Groucho/TLE co-repressor proteins. We have recently established that Drosophila Groucho can inhibit transcription elongation by promoting RNA polymerase pausing shortly after transcription initiation [Kaul et al., 2014. PLOS Genetics. 10(8):e1004595; Kaul et al., 2015. Transcription, 6(1):7-11]. However, we have not established the molecular mechanism through which Groucho promotes RNA polymerase pausing.
We are currently using a combination of techniques in genetics, molecular biology and biochemistry to investigate the molecular mechanisms underlying Groucho-mediated repression, including how it acts to promote RNA polymerase pausing.
Potential students and post-docs who are interested in the areas of gene regulation and/or developmental biology are encouraged to approach Barbara Jennings for further information.