Research Summary

Understanding the role of Exocyst complex in cell division and development in Caenorhabditis elegans

In a multicellular organism, cell division is regulated by cues from the surrounding cells to which it responds.  In turn, the intracellular events/ pathways controlling cell division influence the growth and development.  Both these reciprocal and complementary processes decide the overall development of the organism.  My broad aim is to understand the mechanisms by which intrinsic cell divisions shape organism development, using a well established animal model – Caenorhabditis elegans, a round worm.

The final step of cell division leading to partitioning of the cytoplasm and physical separation of the nascent daughter cells is called cytokinesis.  It is a highly ordered and regulated event during development of multicellular organisms.  In some tissue types, cytokinesis is only partially completed or absent altogether.  Abnormal cytokinesis may result in defects during embryogenesis, stem cell maintenance and gametogenesis. In addition, it can also lead to aneuploidy resulting in tumor formation.  A detailed mechanistic understanding of cytokinesis is therefore imperative to understand its diverse developmental implications.

The focus of my research is a group of proteins collectively known as the Exocyst complex.  It is a highly conserved octameric-complex that is required for cytokinesis in cultured mammalian cells and unicellular yeast.  In multicellular organisms, neither the mechanisms of regulation of cytokinesis by the Exocyst, nor the regulation of Exocyst function itself by developmental cues are understood.  C. elegans strains mutant for the Exocyst components are inviable and sterile, suggesting crucial roles during embryogenesis and germ cell development. Using the power of reverse genetics and live cell imaging in C. elegans in combination with transgenics and proteomics, I would investigate the precise role of Exocyst complex in these two developmental processes.  This work will elucidate 1) the mechanistic basis for cytokinetic regulation by the Exocyst and 2) the consequences of this molecular regulation in determining metazoan development.

Figure Legend: A whole mount fluorescent image of adult C. elegans hermaphrodite showing germ cells and embryos in different stages cell division and of development. Green marks the cell boundary using a membrane marker fused with GFP and red marks the chromatin using a histone protein fused with mCherry.