CytoChem · A Chemical Approach to Understanding Cell Division

Many mechanisms underlying cytokinesis, the final step in cell division, remain poorly understood. The goal of my laboratory is to use chemical biology approaches to address some of the unanswered mechanistic questions by studying cytokinesis at the process, pathway and protein levels. I aim to discover small molecules that specifically target cytokinesis by different mechanisms because they are important tools to study the biology of cell division and could catalyze the discovery of therapeutics.I am proposing here to use small molecules we discovered to study how the Rho pathway regulates cytokinesis. We will synthesize focused libraries around selected compounds to optimize their properties and to identify sites for affinity tags. I am proposing to identify our small molecules’ cellular targets using a combination of approaches, including a new strategy I designed that takes advantage of the fact that they target a discrete signalling pathway.Rho signalling is involved in every step of cytokinesis, but there are many outstanding questions about how this occurs and which proteins are involved. We have completed a genome-wide RNAi screen that has revealed the identity of new proteins connected to Rho signalling. We will combine functional investigations into how these proteins participate in cytokinesis with our newly discovered small molecules. With this array of tools in hand, we expect to use imaging and other cell-based assays to gain of comprehensive understanding of the role of Rho signalling during cytokinesis and other Rho-dependent processes.