Molecular mechanisms of slow axonal transport

Neuronal axons can be a metre long and are maintained for a lifetime, making them acutely vulnerable to defects in microtubule mediated long distance transport. There are two broad categories of axonal transport in neurons, fast and slow.

Slow axonal transport carries at least three times the material of fast transport, but ten to a hundred times more slowly. Protein moved by slow transport can be months old in the distal axon, and this process slows further with aging.

Despite dysfunctional axonal transport being common in neurodegeneration, where aging is the major risk factor for disease, the mechanisms that regulate slow transport are very poorly characterised.

Critically, whether transport time directly affects the accumulated damage and function of its protein cargo is unknown.

The aim of this project is to understand how slow transport is regulated, whether transit time can influence the half-life and function of proteins, and further - whether it’s possible to reverse age-related decline in transport.

To do this I will employ a multidisciplinary approach through the application of single-molecule light microscopy techniques. This project will define the relationship between the machinery of transport and the life cycle of axonal proteins.