Molecular, cellular, and developmental mechanisms of septin disease alleles

PROJECT SUMMARY/ABSTRACT
Cell function and tissue integrity rely on the maintenance of cell shape and organization. The cytoskeleton,
containing polymers and motor proteins, serves to structure and remodel the cell in addition to facilitating
tissue architecture. A conserved filament-forming family, the septins, influences the cytoskeleton by serving as
a protein scaffold and septin dysregulation may promote many human diseases. The goal of this proposal is to
understand how septins contribute to cell and tissue behavior and organization through the use of septin
alleles found in human disease. I will combine high-resolution imaging, cell biology, molecular biology,
developmental biology, genome editing, and biophysics to achieve the forestated goal. My work will be directed
by three aims: (1) Investigate how clinical septin mutations and depletion affect tissue organization and
function; (2) Elucidate how septin mutations perturb cytokinesis; (3) Define how septin mutation affects
polymerization and higher-order structure function. The proposed experiments will establish the use of C.
elegans as an in vivo system to overcome current limitations surrounding septin study and will provide insight
into how septin dysfunction can perturb cell and tissue organization and function during human disease.