While many small molecules can diffuse to reach where they are needed inside the cell, larger molecules and organelles need to be actively transported. This is accomplished by a set of specialized motor proteins that haul the cargoes to where they are needed by stepping along a network of intracellular filaments (microtubules and actin filaments) (see figure 1). Examples of transported cargoes include mRNA particles, mitochondria, endosomes and phagosomes, various vesicles and lipid droplets. Cargoes are not always benign; pathogens like virus particles hijack the molecular motors of the cell that in turn deliver them to the nucleus where they can use the cellular machinery to replicate. Given the wide variety of cargoes that need to be transported, any failure of the transport machinery can affect many cellular processes and lead to disease. Yet, the molecular mechanisms relating failure of motor regulation to disease remain largely unknown.

We use a combination of biophysical, biochemical and genetic approaches to study motor regulation in relation to neurodegenerative diseases. In particular, we currently study how the kinase, Glycogen Synthase Kinase-3 (GSK-3) which is highly active in Alzheimer’s patients’ brains, alters transport by molecular motors in axons.