Epifluorescence microscope

C. elegans hermaphrodites on E. coli

C. elegans in artificial dirt PDMS chip

A caravan in a cable: cargo transport within neurons

Animal bodies are highly wired for information processing and communication – axons are the “cables” carrying electrical signals arising from neurons. Each axon connects the cell body of a neuron to a synapse, the latter being crucial in transmitting information from the neuron to other cells. Along with synapses, axons form a complex network of such cables interconnecting all parts of the body enables behaviours that range from the simplest reflex reaction, to being able to perceive and make sense of the assortment of symbols on this very page. Axons are true bio-cables – they’re very much alive and in constant communication with both the cell body of the neuron from which they project, and the synapse where they terminate. The inside of such a cable is a whole world humming with activity. The “cable road crew” needs to move many cargoes along the entire axon for smooth flow of information along this “information highway.” The crew faces many challenges, not the least being the distances between cell body and synapse: some human axons are half the body length! Long-distance transport is made possible by a dedicated “trackwork system” of microtubules. Many kinds of cargo need to be moved along the crowded tracks, both in the forward direction from the neuronal cell body to the synapse, and in the backward direction from the synapse to the cell body. There are two classes of molecular motors to do the ferrying, kinesins for forward travel and largely dyneins for backward travel. All these “vehicles” and their “passengers” have to appropriately recognize each other, travel to the correct destination and part company upon reaching there. Moreover, many axons give off branches along the way, so yet another challenge is directing traffic at junctions in the tracks.

Our lab focuses on understanding how axonal cargo transport is regulated. We use the classic model animal C. elegans. Applying a combination of genetic, molecular and in vivo imaging approaches (see our movies), our work has revealed for the first time how certain motors are regulated at synapses. We are now working to track down novel players that regulate cargo transport in neurons. While we are engaged largely in basic research, a lot of what we do has significant implications for understanding neurodegenerative diseases in humans. Parallels between pathologies seen in transport-challenged C. elegans mutants on one hand and motor neuron disease of humans on the other hand underscore the value of research in an important area whose complexity continues to fascinate and challenge researchers.