Molecular mechanisms controlling germline stem cell biology (360G-Wellcome-206257_Z_17_Z)

The ability of stem cells to replenish and differentiate is critical for tissue growth, repair, and homeostasis. Yet, our understanding of the molecular mechanisms governing stem cell fate transitions remains limited. Through a systematic RNAi screen using the Drosophila germline as a model for stem cell biology, I uncovered a central role for ribosome biogenesis and protein synthesis regulation in controlling fate transitions. My current goal is to dissect the molecular mechanisms by which protein synthesis control - a new frontier in genomic regulation - governs stem cell maintenance and differentiation in vivo. In particular, I propose to generate a systematic and detailed translation-based roadmap of the differentiation process. This will be achieved by coupling genetic tools with high-throughput techniques, and aims to determine the set of actively translated mRNAs at consecutive differentiation stages. This unbiased approach will allow me to reveal the set of regulated targets and to uncover the cascades dictating fate transitions during germline differentiation. In parallel, I will combine developmental and molecular analysis to explore the mechanisms by which specific translation regulators support key developmental aspects. Dissecting such regulatory mechanisms will provide new insights into the principles dictating stem cell fate transitions in vivo.