The role of FUS phase transition in axonal mRNA localisation and translation

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases leading to behavioural and cognitive impairments. Many essential proteins are produced locally in axons (neuronal extensions), and in disease-affected axons, protein aggregation interferes with local protein synthesis and causes neuronal death. However, it remains unclear whether these aberrant aggregates are the direct cause of defective protein synthesis and axon death. 

I will investigate this question using a light-controlled tool to induce protein assemblies in one of the two forms – stable aggregates found in disease cells, or less stable granules present in normal cells. I will compare the differences in local protein synthesis and axon survival in neurons carrying different forms of protein assemblies. I also intend to identify novel disease-associated proteins, the synthesis of which is affected by the presence of aggregates. 

My findings will potentially provide new opportunities for the development of effective treatments.