Research Interests

What is the molecular basis of intracellular transport? We have approached this question using the genetic techniques in Caenorhabditis elegans. In higher organisms intracellular motility is mediated through motor proteins such as dynein, kinesin and myosin, which transduce chemical energy in ATP into mechanical force along microtubules or microfilaments. Kinesins form a large family of microtubule based motors, which mediate intracellular transport including vesicle delivery, ciliary growth, and chromosomal movement during cell cycle. All kinesins share a highly conserved globular motor of about 350 amino acids, but vary considerably in the size and structure of the tail domain. We have brought to light genes encoding for all known kinesin subfamilies found in higher organisms in the nematode C. elegans (viz klp-1-klp-20), by a combination of genetic and molecular approaches. Consequently, the simple nematode provides an excellent model to elucidate the relationship between structure and function for all kinesin motors within a single, well studied animal. Our results suggest that the nematode kinesins perform highly specialized cellular functions in cilliary and axonal growth, neurotransmitter vesicle transport, chromosomal movement during meiosis and mitosis. Most of these in vivo functions are conserved in species as divergent as the nematode and humans. We are therefore, pursuing the role of cellular motors and related cytoskeletal proteins such as tublulin and actin in the generation of cellular polarity, with a focus on intracellular transport in endothelial cells.