Infants born preterm (7-10% of all births in the EU) are at a markedly increased risk of perinatal brain injury; for example, birth at <28 weeks gestation is accompanied by a 80-fold increased risk of developing severe brain injury, cerebral palsy (CP), and 45% of all cases of CP occurs in infants after preterm delivery. Hence, CP is the commonest cause of severe disability in children (2-3/1000 births), over 17 million sufferers worldwide representing a major cost to sufferers, their families and society. A leading cause of preterm birth and brain damage in preterm infants is exposure to systemic inflammation (maternal/fetal infection, infection occurring during their time in hospital), which induces inflammation within the brain. Inflammation within the brain plays a central role in perinatal brain injury as it impairs the development of oligodendrocytes; the cells that will produce myelin that permits high-speed transfer of information between neurons. Microglia (MG), the immune cells of the brain, orchestrate the inflammatory response to diverse insults but these cells can exhibit both beneficial and detrimental functions for the developing brain. Up to date the cellular mechanisms that govern these opposite functions are poorly understood. Novel insights are highly needed and indispensable in order to prevent the deleterious functions of MG and modulate them into neurosupportive functions. To date, the metabolic features (the way cells use different types of energy supply) of MG in their different functions have not been investigated, although it is increasingly clear that in several cell types metabolic activities has a key impact on cellular functions. Our goals are, by combining teams with complementary expertise, i) to understand the links between metabolic features and MG functions, ii) to identify the gens that are responsible for these mechanisms, iii) to selectively block key metabolic pathways by genetic or pharmacological tools and assess the consequences on MG functions, and iv) to manipulate key metabolic pathways in MG in a mouse model relevant to perinatal brain damage. These studies will help to unravel the complex MG functions and to find targets to combat perinatal brain injury but also the multitude of degenerative neurological disorders associated with inappropriate MG functions