Characterising a novel candidate gene regulating ageing related atrophy in neurons

The societal challenge of an increasing ageing population requires better
understanding of the fundamental cellular pathways that underlie the
ageing process. Recently discovered inherited mutations in cellular
membrane trafficking pathways cause cognitive dysfunction in dementia,
but are also likely to be compromised in normal ageing. The pathogenic
signals arising from endosomal dysfunction are poorly understood. To
understand the interaction between ageing and endosomal dysfunction
we study Frontotemporal Dementia (FTD), a cause of early-onset
dementia. Using a Drosophila model of FTD, we identified novel
conserved molecules and signaling processes contributing to neuronal
atrophy and death (West et al., (2015) J. Cell Biol. 208: 931-47).
Candidate genes from our screen identify endosomal processes and
synapse growth regulation, amongst them a neuronal transmembrane
protein contributing to FTD progression. The student will work in the
Evans lab studying the role of this novel protein using an in vitro tissue
culture and high-resolution imaging approach, and in the Sweeney lab
using Drosophila genetics, CAS9/CRISPR and high resolution imaging to
uncover the cross talk between synaptic growth signals and apoptosis.
These genetic and cell biological analyses will dissect a role for the
transmembrane protein in the progression of FTD and neuronal survival.