Abstract: The first part of the lecture will focus on the structural biology of riboswitches, mRNA elements consisting of a sensing domain and an expression platform, that undergo conformational changes on metabolite binding, and utilize on-off switches to control gene expression. The lecture will next describe recent research on the structural biology of argonaute proteins, their binary complex with guide strand and ternary complex with added target strand, thereby providing insights into nucleation, propagation and cleavage events associated with RNA silencing. The second part of the lecture will focus on recognition events controlling epigenetic regulation mediated by methylation marks on histone tails and at CpG steps on DNA. The lecture will describe the recognition principles that allow the jumenji family histone lysine demethylase JHDM1A to site-specifically demethylate lower methylation states of histone H3 methylated at lysine 36. The lecture will next describe the recently determined structure of an autoinhibitory DNMT1-DNA complex, thereby formulating a two-state model of eukaryotic maintenanace DNA methylation.
Dr. Patel's group applies crystallographic and solution NMR techniques to investigate macromolecular-mediated recognition, regulation and catalysis. The major thrust of the laboratory is currently in the structural biology of RNA silencing and the histone/epigenetics code. Significant efforts are also underway towards a molecular understanding of RNA-mediated events involving riboswitches and ribozymes, as well as protein-RNA recognition events impacting on disease syndromes. Other projects include higher order DNA architectures with an emphasis on DNA quadruplexes, and the replication of DNA damage sites by bypass polymerases. Finally, our group also studies the molecular basis of glycosphingolipid binding specificity.
CSSB Distinguished Lecture Series: Fall 2010
09/14/2010 - Dinshaw J. Patel, Memorial Sloan-Kettering Cancer Institute
09/21/2010 - Andrea Califano, Columbia University
10/12/2010 - Bruce Berne, Columbia University
10/26/2010 - Gary Siuzdak, The Scripps Research Institute
11/09/2010 - Charles Cantor, Boston University
11/11/2010 - Kristin Brown, GlaxoSmithKline
11/30/2010 - JoAnne Stubbe, MIT