Sachin Kotak

Assistant Professor
Microbiology and Cell Biology
Research Areas: 
Uncovering the role of the plasma membrane lipids in mitotic spindle behavior, Identifying novel modulators of spindle positioning
Research Highlights: 

How cells divide (or undergo mitosis) has fascinated researchers for over a century. Proper positioning and elongation of the mitotic spindle during metaphase and in anaphase are critical processes for determining the correct placement of the cytokinetic furrow. These processes further ensure that the cell fate determinants are appropriately segregated in daughter cells during asymmetric cell division, including in thestem cell lineages. A plethora of evidence from different experimental model systems indicates that spindle positioning is often dictated by an evolutionarily conserved ternary complex (NuMA/LGN/Gαi1-3in Homo sapiens and LIN-5/GPR-1/2/ in Caenorhabditis elegans). This complex promotes the binding of the minus-end directed microtubule-dependent motor protein dynein at the cell cortex. Such cortically anchored dynein is thought to regulate spindle positioning by exerting a pulling force on theastral microtubules.We have demonstrated that the levels of cortical dynein must be tightly regulated for proper spindle positioning both in human cells and C. elegans embryos. However, despite our basic understanding of the key players involved in spindle positioning, the mechanisms that spatially and temporally regulate the cortical levels of the ternary complex and/or dynein, as cells progress through mitosis, are not well delineated. Our main research objective is to understand the mechanisms of spindle positioning and elongation using two evolutionarily divergent cellular model systems of human cells and C. elegans embryos. These objectives will be achieved by utilizing multifaceted cell biology, biochemistry, and genetics approaches.

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