This award aims to develop a single-cell atlas of brain metabolism in Drosophila, in both healthy and metabolically stressed conditions, replacing the use of mice in some studies.
Nutrient restriction in pregnancy can lead to restricted foetal growth, but in many cases the brain is ‘spared’ and less affected than the rest of the body. The protective processes that allow this to happen are not well understood but can potentially result in neural disorders later in life. In vivo studies in mice are the gold standard experimental model for inducing foetal growth restriction. Metabolic stresses are induced during the animals’ pregnancy either through diet restrictions or inducing hypoxia using surgical interventions or hypoxic chambers. Dr Alex Gould and colleagues have previously established a replacement model for mechanistic studies of brain sparing using Drosophila, which possess the three main types of cells found in the human brain. Drosophila are not currently considered capable of suffering and so can be used as an alternative for mammalian models.
With NC3Rs funding, Alex will work with Dr Adrien Franchet, a postdoctoral fellow, to use single-cell sequencing to produce the first atlas of Drosophila brain metabolism. They will combine RNAi and gene expression data to compare normal and metabolically stressed Drosophila. The Drosophila CNS Stressome Atlas will be made available to all researchers as an open-access resource to generate new hypotheses about brain sparing and metabolic interactions in the brain, without the need for initial exploratory studies to be performed in genetically modified mouse models.