Molecular Mechanisms of Non-muscle Myosin II Contractility

The overarching goal of this proposal is to understand the mechanisms that regulate NMII contractility. Project 1 explores a potential novel NMII binding protein, Split Discs (Spdi), whose human homolog SPECC11L is implicated in cranial-facial pathologies. The hypothesis is that Spdi binds NMII to regulate its contractility. This project involves biochemical characterization and cell biology experiments to elucidate the mechanism by which Spdi associates with NMII, and employs an ex-vivo developmental model to understand how its regulation of contractility affects collective cell migration. Project 2 focuses on the role of acetylation on the regulation of NMII filament assembly, hypothesizing it plays an important role alongside phosphorylation. This project will identify the enzymes involved in the acetylation-deacetylation cycle and elucidate the role this post-translational modification has on force generation. The research integrates high-resolution microscopy and capitalizes on Drosophila and its broad genetic tools.