My laboratory is applying genetic, molecular and biochemical approaches in Drosophila to study the function and regulation of cytoplasmic dynein. Cytoplasmic dynein contains a homodimer of the motor subunit that generates force against the microtubule substrate. In addition, a complex of accessory subunits at the base of the motor subunit is thought to mediate the attachment of dynein to a variety of cellular cargoes. In one line of investigation, the lab is testing the hypothesis that the subunits within the multi-protein motor complex are specialized in their functions. If different subunits act in different processes, then the phenotypes associated with mutations in each subunit may differ. The phenotypes associated with mutations in each subunit are being characterized using living cell microscopy and biochemical approaches. On a genomic scale, modifier screens have identified candidate genes that may reveal novel dynein functions and regulatory pathways. For example, the gene encoding a cytoplasmic transmembrane protein involved in EGFR signaling has been identified as a modifier of dynaction function. Defects in vesicle trafficking through the secretory or endosomal pathways may impact EGFR signaling. Understanding the mechanistic basis for the genetic interactions between identified modifier loci and the dynein pathway remains an important goal for the laboratory.
In more recent work, the lab is examining the role for dynein in chromosome attachment and cell cycle checkpoint controls. In another area, using mutations in the Drosophila dynein heavy chain, we see that cytoplasmic dynein is required for the asymmetric cell divisions that give rise to the oocyte. The loss of dynein function results in the failure to specify an oocyte. We are further investigating the hypothesis that dynein and other motor proteins are utilized in the intracellular transport of morphogens required for proper maturation of the egg.