Abstract
Genome-wide or epigenome-wide association studies (GWAS or EWAS) of Alzheimer’s disease (AD) have identified several genes associated with increased risk of AD. However, their causal role and contribution to disease pathology, remains largely unknown. Dr James Hodge will discuss using Drosophila as a system to functionally screen through the top hits identified by EWAS or GWAS for AD, revealing which cause disease-relevant phenotypes such as neurodegeneration, shortened life, progressive changes in movement, memory, sleep, circadian rhythms and clock neuron excitability. We are currently characterizing these risk genes further to identify novel mechanisms, targets and drugs. Finally, Dr Edgar Buhl will discuss how the molecular clock controls the expression of ion channel genes in the clock regulating circadian changes in clock neuron excitability. We call this the membrane clock which functions to transmit time-of-day information through the clock neuronal circuit and beyond. We are determining the components and mechanism of the membrane clock using Drosophila, mouse and in silico models testing the hypothesis that there is a conserved set of ion channels that generate daily electrical variations in fly and mouse clock neurons.