Research Summary

Role of Dynactin and Lis1 in Dynein driven transport of phagosomes

Most key cellular processes require intracellular transport of molecules to different regions of the cell. Long-range intracellular transport is generally achieved by microtubules and motors: Kinesin and Dynein. Our lab has shown that unlike Kinesins, the Dynein motor functions in teams during transport of phagosomes and endosomes. Broadly, we are interested in understanding molecular factors and mechanisms that govern this team behavior of Dynein during the process of phagosomal maturation in Dictyostelium

In particular, we will determine the role of two major Dynein regulators:  Dynactin and Lis1. These regulators are essential for most Dynein driven transport processes in vivo. However, how they affect Dynein motors in a team is not clear. Another unique property of Dynein is to tenaciously bind microtubules when load increases. This property is called catch-bonding. We want to determine whether this allosteric property makes Dynein suitable to work efficiently as a team as opposed to other motors. Optical trapping along with other biochemical approaches will be used to address these questions.

Our findings will help in understanding different aspects of co-operative Dynein function. These studies can further be extended to understand diseases caused by Mycobacterium tuberculosis and Leishmania, pathogens that inhibit Dynein driven transport of phagosomes in vivo.