Michael Laub, MIT/HHMI, Specificity and Evolution of Signaling Pathways
Our lab is interested in the specificity and evolution of signaling pathways. We study two-component signal transduction systems, the predominant form of signaling in bacteria, which involve sensor histidine kinases and their cognate substrates. We have previously shown that the specificity of kinase-substrate interactions is dictated at the level of molecular recognition and relies on a relatively small set of interfacial residues. We are now probing the evolution of kinase-substrate specificity by focusing on changes that occur to these residues. We are examining the selective pressures that influence these residues and, in particular, trying to understand how gene duplication impacts specificity. For example, how are the proteins produced following a duplication event insulated from one another and from other existing pathways? Can we infer the mutational trajectories followed by duplicates and what, if anything, constrains these trajectories? Finally, we have developed a deep-sequencing based approach to systematically map the sequence space defined by these specificity residues.
Location: Carl Icahn Lab 101
Date/Time: 09/24/12 at 4:15 pm - 09/24/12 at 5:15 pm
Category: Quantitative & Computational Biology
Department: Lewis-Sigler Institute