Defining the local and systemic metabolic networks underpinning male gametogenesis

Somatic cells support gamete development and ensure adaptation to nutrient conditions through an intricate network of intercellular metabolite transfer. Yet we understand little about this network or the somatic metabolism that underpins germline development. Using the Drosophila testis, we showed in vivo for the first time that germline survival depends on somatic lactate production and transfer, a hypothesis first proposed from in vitro studies in mammals, highlighting a remarkable degree of evolutionary conservation and the tractability of our model. Here, we will explore the metabolic pathways that sustain gametogenesis in both germline and soma. In Aim 1, we will define germ cell metabolism, by first addressing how lactate is used in germ cells, a question that remains unsolved in mammals and flies. Aim 2 will establish the metabolic needs of gonadal somatic cells focusing on fatty acid oxidation which we have shown is important for differentiation. Aim 3 will address the mechanisms by which a distant somatic tissue, the fat body, controls the adaptation of the testis to nutrient levels. Overall, by studying germline metabolism not in isolation but in the context of intercellular metabolic networks, this project will provide a comprehensive understanding of the metabolic requirements of male reproduction.