R. Dyche Mullins, Ph.D.

Research

We study the regulation and dynamics of the actin cytoskeleton; that is, how living cells establish polarity and use actin polymerization to change shape or propel themselves forward.Amoeboid cell motility can be divided in to three main components: (1) What are the structures of the macromolecular assemblies that drive cell movement and shape change and how does the cell construct them? (2) What is the mechanism by which molecular assemblies generate the force required to deform cell membranes? (3) How do intracellular signaling systems control the assembly and function of these macromolecular machines? We are interested in all three questions. The basic processes we study are conserved across all eukaryotic phyla and we study them in several organisms including free-living soil amoebas, budding yeast, fruit flies, and mammals. The forward, or leading edge of a motile cell is a highly specialized structure - containing an extremely dense meshwork of actin filaments built and maintained by a particular subset of actin-associated proteins. Filaments assemble at the membrane and drive it forward (Mogilner and Oster 1996) and behind the advancing membrane filaments are disassembled (Theriot and Mitchison 1991) so that the actin network at the leading edge churns forward. We do not understand exactly how extracellular signals are converted into three dimensional structures that accomplish specific tasks but we suspect that the basic principles, if not the molecular mechanisms, are conserved across evolution Here are a few questions we are pondering right now: 1) What is the molecular mechanism of Arp2/3 activation? 2) How does actin assembly induce polarity and generate force? 3) Novel mechanisms of actin assembly 4). Structure and function of the prokaryotic cytoskeleton.