Defining function for novel cellular effectors of autophagy regulating synapse growth in Frontotemporal Dementia

Frontotemporal Dementia (FTD) is a major cause of early onset dementia. Characterised by atrophy of the frontal and temporal lobes with loss in language and social function, FTD incidence has a strong dominant genetic component. Recently FTD has been placed in a disease spectrum with Amyotrophic Lateral Sclerosis (ALS or Motorneuron Disease) suggesting a common pathogenic mechanism. A number of loci for FTD and ALS have been mapped. Among these are proteins regulating autophagy. In a screen in Drosophila, we have identified novel conserved molecules and signaling processes contributing to FTD pathogenesis and disrupted neural function (West et al., (2015) J. Cell Biol. 208: 931-47, Lu et al., (2013) Mol Cell, 52:264-271, Ahmad et al., (2009) PNAS 106: 12168-71). Novel identified genes from our screen appear to be involved in autophagic processes and synapse growth regulation. Interestingly we find in these mutants that nutritional status regulates synaptic expansion. This is a novel and unexpected aspect of synaptic growth regulation that will be explored in this PhD project. The student will work between the Evans lab, studying the role of these novel proteins in autophagy using an in vitro tissue culture and high resolution imaging approach, and the Sweeney lab, using Drosophila genetics to uncover the role of autophagy and nutritional status in the progression of FTD/ALS. We are looking for an ambitious and hard working student for this cutting edge project. The student will gain experience in tissue culture, high-resolution imaging, molecular biology, CAS9/CRISPR genome engineering and functional genetics.