Investigating the molecular basis for selective vulnerability in FET-linked Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD)

Dysfunctional RNA metabolism has emerged as a common characteristic in neurodegeneration with mutated RNA binding proteins having been identified as the genetic cause of several neurodegenerative or neurodevelopmental disorders (Nussbacher et al., 2015). Among these RNA binding proteins are Fused in Sarcoma (FUS), Ewing Sarcoma (EWS), and TATA-Box Binding Protein Associated Factor 15 (TAF15), which are highly conserved multifunctional nucleocytoplasmic shuttling proteins that form the so-called FET family (Riggi et al., 2007; Tan and Manley, 2009).

The main aims of this project are to gain insight into the cell type specific expression of the FET proteins in the CNS throughout ageing in health and in the context of FET-linked Frontotemporal Dementia in patient tissue. These interlinked aims can be summarised as follows.

Temporospatial analysis of FET protein expression throughout the brain and spinal cord of young and aged mice using microscopy.

Temporospatial analysis of FET gene expression throughout the brain and spinal cord of young and aged mice using RT-qPCR

Comparative analysis of FET protein expression in human control and ALS/FTD vulnerable and resistant patient tissue.