Cell motility and cytoskeleton

Work done by muscle and non-muscle cells requires the transduction of chemical into mechanical energy. This function is carried out by actin, tubulin, and a family of motor proteins. The interactions between these proteins and the changes in their structure constitute the molecular basis for force generation and motility in muscle and non-muscle cells. Our goal of elucidating the mechanism of contractile processes is pursued at two levels. At the molecular level, we are concerned with the structural and dynamic properties of the contractile proteins. We explore structure-function relationships in actin, myosin and other proteins by biochemical, biophysical, immunochemical, mutational, and in the vitro motility and force measurements. Intermediate steps in the contractile process are probed with the help of nucleotide analogues, specific antibodies, synthetic peptides, and appropriate mutants of the key proteins. The aim of these studies is to obtain a structural description of the mechanism of motion and force generation by motor proteins., At the cellular level, we study the function, interactions, and structural transitions of the assembled protein systems.

Many filamentous cellular structures are constructed from their components through fine-tuned assembly processes. The biological function of these filaments is frequently linked to the signaling and the regulation of assembly by cellular factors. Our interest is focused on the formation and remodeling of actin filaments, bundles, and networks by actin binding proteins. The mechanisms of the assembly reactions and the structural changes which govern them are studied by biophysical, biochemical, and electron microscopy methods. To understand the regulation of actin assembly by other proteins, macromolecular contact sites are investigated by a wide spectrum of experimental techniques.