The goal of this research is to elucidate fundamental mechanisms of biological self-organization, focusing on the rules that govern dynamics and organization of cellular actin structures. This question will be addressed using as a model system the polarized actin cables assembled in budding yeast. The proposal seeks to understand how 8-10 different conserved actin-regulatory proteins, each with a distinct functional role, work in concert to polymerize, stabilize, bundle, and dynamically turnover actin cables, endowing these structures with a characteristic length, architecture, and dynamics. The project combines in vitro reconstitution, genetics, live-cell imaging, multi-wavelength single molecule TIRF microscopy, structured illumination microscopy, and 4D confocal microscopy.
The Aims are: (1) Use a novel in vitro actin cable reconstitution assay to dissect the mechanisms underlying cable assembly, turnover, and steady-state length control; and (2) Define the mechanisms controlling actin cable assembly, turnover, and architecture in vivo.
Relevance to Public Health: The research in this proposal investigates basic principles of self-organization underlying the formation of cellular actin cytoskeleton networks. More specifically, the proposal focuses on nine proteins (Formin, Profilin, Tropomyosin, Capping Protein, Coronin, Cofilin, AIP1, Srv2/CAP, and Twinfilin) that control the assembly and turnover of dynamic actin cables. The work is directly relevant to public health because altered expression levels of these proteins (Tropomyosin, Cofilin, Coronin, Srv2/CAP, and Twinfilin) are linked to childhood brain cancers, Alzheimer's disease, breast cancer, and chronic obstructive pulmonary disease, and lymphoma metastasis.
