Abstract
Protein-protein interactions are critical to the operation and functions of all cells. The specificity of these interactions is often dictated at the level of molecular recognition, meaning proteins have an intrinsic ability to discriminate cognate from non-cognate partners. Understanding precisely how this discrimination is accomplished remains a major problem, particularly for paralogous protein families in which the individual members share high sequence and structural similarity. Our work tackles this problem primarily in the context of two-component signal transduction systems, the predominant form of signaling in bacteria. I will describe our work using analyses of amino acid coevolution to pinpoint the molecular basis of specificity in these proteins. This work has demonstrated that a relatively limited number of residues dictate interaction specificity and they have enabled the rational rewiring of signaling pathways. Additionally, these studies set up our more recent efforts to systematically map the sequence spaces that underpin two-component signaling, which have shed further light on the specificity and evolution of these protein-protein interactions.
Biography
Dr. Laub earned his PhD in Developmental Biology at Stanford University in 2002 working in the lab of Lucy Shapiro on the bacterial cell cycle. He then took a Fellow position at Harvard University in the FAS Center for Systems Biology where he continued working on the cell cycle, while also initiating work on understanding the specificity and evolution of bacterial signaling pathways. In 2006, Dr. Laub joined the faculty at MIT in the Department of Biology where he is an Associate Professor. Since 2008 he has also been an Early Career Scientist of the Howard Hughes Medical Institute.