Welcome to the Kovar Lab
Cells utilize diverse actin cytoskeleton networks with distinct architectures and dynamics to facilitate fundamental processes such as polarization, endocytosis, motility and division. The particular characteristics of different networks (actin filament density, organization and dynamics) are determined through the coordination action of specific sets of actin binding proteins (ABPs) with complementary binding properties and activities. Moreover, cells typically assemble and maintain multiple F-actin networks simultaneously within the same cytoplasm. Consequently, F-actin networks must self-organize from a common pool of shared actin monomers and overlapping sets of ABPs. We predict that there is important crosstalk (interactions) between networks that are critical for their form and function. Our long-term goal is to discover the direct and indirect interactions between self-organized F-actin networks, which are required for establishing their unique identities and functions within a common cytoplasm, and to determine the underlying molecular mechanistic principles that govern these interactions. We investigate actin cytoskeleton network self-organization utilizing an array of complementary quantitative approaches including (1) genetics and live cell fluorescent microscopy, (2) multi-color single molecule imaging of in vitro actin filament networks reconstituted from ensembles of ABPs, and (3) mathematical modeling.
Movie 1: Effects of addition and washout of the Arp2/3 complex inhibitor CK-666 on fission yeast cells expressing the general F-actin marker Lifeact-GFP. Movie courtesy of Dr. Tom Burke
Movie 2: Actin (Green) elongating while Fascin (Red) and α-Actinin (unlabeled) segregate into mutually exclusive domains on two-filament bundles. Movie courtesy of Dr. Jon Winkelman
Movie 3: TIRF microscopy imaging of cyan-labeled fimbrin (Fim1) molecules bundling green-labeled actin filaments inducing cooperative removal of magenta-labeled tropomyosin (Cdc8). Movie courtesy of Dr. Jenna Christensen