Functional characterisation of human synapse genes expressed in the Drosophila brain, applications in drug screening. Matt B. Mahoney, Lysimachos Zografos, R. Wayne Davies, J. Douglas Armstrong. Brainwave Discovery, LTD, Ardshiel, Main Street, Gartmore, FK8 3RJ, United Kingdom.

   Brainwave Discovery, Ltd specialises in the rapid development of in vivo brain assays for chemicals acting on human central nervous system (CNS) targets. We use our expertise in "humanising" transgenic fruit flies (D. melanogaster) and expressing the human protein with spatial and temporal control in the insect brain. We have also developed and streamlined an array of phenotyping assays (climbing, courtship, neuronal activity) as well as histology methods in order to quantify and assess the effect of chemicals on fruit fly models of mental and neurodegenerative disease. Also, as part of the SynSys project (www.synsys.eu), in order to identify novel gene variants as disease associated candidates, we have selected and prioritised a list of human synaptic genes and variants (SNPs, mutants). Using the aforementioned fruit fly humanising and phenotyping pipeline we expressed these genes in the fruit fly CNS and tested for behavioural phenotypes, ranging from simple (i.e. climbing) through to more complex (i.e. courtship learning). In this work we will present the basic outline of our pipeline and how this has been applied to screen for synaptic genes involved in learning and memory or neurodegeneration processes. We will also show results underlining how these models can be used as excellent and rapid primary drug screening platforms enabling drug research and development divisions of pharmaceutical companies to make faster, cheaper and better informed decisions earlier in the drug discovery pathway.