Michigan Technological University
United States of America
Our multi-disciplinary research program aims to understand the molecular architecture and recognition features of the early events in transcription initiation, and to use these insights to develop inhibitors of transcriptional assembly. A growing number of studies are finding diverse and essential roles for molecular recognition events in mediating information transfer and complex assembly in biology. In fact, biological outcomes are often due to physical interactions between proteins that are so highly selective that seemingly minor chemical modifications (i.e. methylation, acetylation or phosphorylation) can completely abolish biomolecular recognition processes and redirect signaling pathways. In principle, development of small molecule inhibitors of interactions of specific transcriptional activators (or repressors) with DNA or with the basal transcription machinery could provide highly selective regulators of gene expression and thus highly selective therapeutic agents (e.g., antiviral agents based on disabling essential viral gene expression).
Understanding the molecular recognition features and assembly mechanisms of gene regulation
Kupitz, C., Chandrasekaran, R., and Thompson, M. (2008) Kinetic analysis of acetylation- dependent Pb1 bromodomain-histone interactions. Biophys. Chem. 136, 7-12.
Thompson, M. (2009) Polybromo-1: the chromatin targeting subunit of the PBAF complex. Biochimie. 91, 309-319.
Thompson, M. (2009) Thermodynamic and kinetic analysis of bromodomain-histone interactions. Methods in Enzymology, Biothermodynamics, Part B, 466. In press.