Targeting the nucleo-cytoplasmic transport machinery in sporadic and familial ALS

Cytoplasmic mislocalisation of TDP-43 is a pathological hallmark of nearly all sporadic and familial ALS patients. Animal models have shown that aggregation in the cytoplasm leads to neuron death and muscle degeneration and that clearance of these cytoplasmic aggregates is beneficial. The mechanisms that drive mislocalisation into the cytoplasm however remain elusive but are of immense therapeutic interest as they provide critical insight into disease etiology. This project will build on an existing platform to investigate these fundamental characteristics of TDP-43 mislocalisation and intracellular transport in vivo. We will make an important contribution by unraveling the cellular mechanisms that underpin the cause and progression of sporadic and familial ALS.