Investigating the role of TDP-43 in ALS
About the project
We aim to elucidate the cellular mechanisms that cause the motor neurone disease amyotrophic lateral sclerosis (ALS). It is established that in >95% of ALS cases, the RNA/DNA-binding protein TDP-43 mislocalises to the cytoplasm and forms insoluble protein aggregates in affected neurons. It is unclear how TDP-43 relates to the onset and progression of disease. Our lab strives to identify pathways that control TDP-43 mislocalisation, aggregation and disease progression. To do this, we use a variety of approaches including genetics of the fruit fly, in vitro biochemical techniques, mammalian cell and neuronal culture systems with neuropathology of the human spinal cord.
Currently, we are focused on understanding how the poly(ADP-ribose) polymerases and various stress-related proteins control TDP-43 and whether pharmacological strategies that target these pathways could have therapeutic potential in ALS.