How does soma-germline metabolic communication promote fertility?

Cellular metabolism involves the breakdown of nutrients to produce energy and building blocks for complex molecules. Carbohydrates provide much of the energetic fuel: blood sugars are imported into cells to undergo a process called glycolysis, breaking down glucose into pyruvate, which is then used to power the mitochondrial citric acid cycle, leading to respiration and energy production. However, there is increasing evidence that cells and organs have distinct metabolic activities. Within an organism, metabolic reactions are compartmentalised: some cells take up circulating sugars and provide other cells with derived products. It is still poorly understood how cellular metabolism is set up so that some cells are able to produce metabolites to support other cells while also meeting their own needs. Importantly, it is also unclear why this compartmentalisation takes place; in other words, why are some cells so dependent on secondary metabolites? Nowhere is it more important to support cells properly than in the gonads, where germ cells produce the gametes (egg and sperm) that enable species survival. In mammals, male germ cells depend on secondary metabolites provided to them by somatic support cells and cannot use blood sugars as a nutrient source. Here we propose to use the fruit fly Drosophila as a model to understand the particular metabolic needs of male germ cells. We have established that metabolic support of germ cells in testes is conserved, and that somatic support cells, called cyst cells, conduct glycolysis to sustain germ cell survival in flies. The genetic tractability of Drosophila makes it an ideal model to understand how the metabolic interplay between somatic support cells and germ cells enables proper germ cell development and thus fertility, while conforming with the BBSRC priority of replacement, refinement and reduction of animal use in the context of bioscience for an integrated understanding of health. In the work we propose here, we will address firstly which metabolites are supplied to the germline by the somatic support cells and how they pass between cells; secondly, we will determine how somatic cells ensure that metabolites derived from circulating sugars are dedicated to supporting the germline and kept separate from those fuelling the somatic cells' own energetic needs; and thirdly, we will characterise how these secondary metabolites are used in the germline, answering the question of why such a compartmentalisation of metabolism exists in the testis. This research falls within the BBSRC's key challenge area of "nutrition for health" and the "food, nutrition and health" strategic priority, as it will lead to a greater understanding of how carbohydrate metabolism influences cellular processes in the germline and how it varies across different cell types. Our findings will have important implications on understanding gonadal biology, by untangling the metabolic interplay between the somatic and germ cells that compose the gonad. Knowing both how the soma acts to provide metabolic support and what the need is in the germline will provide fertile new avenues for beneficial interventions to improve fertility.