Adult stem cells (SCs), also known as tissue SCs, support tissue homeostasis and repair throughout the entire life of the organism. The remarkable longevity of tissue SCs relies on their unique ability to asymmetrically generate new SCs (self-renewal) as well as specialized cell types (differentiation). Notably, many genes that signal to regulate the balance between renewal and differentiation encode proteins as well as small RNA molecules, predicted to regulate specific mRNAs. This proposal is aimed to uncover RNA regulation networks essential for maintaining an adult germline stem cells (GSCs) pool, and for preventing differentiation along the germline lineage. Ultimately, I wish to understand in molecular details how the activities of diverse post-transcriptional factors are coordinated in space and time to give a functional tissue homeostasis. Using the Drosophila testis - a stem cell based tissue model in which stem cells and the niche have been defined and can be manipulated, I aim to investigate SCs regulation by conserved RNA regulators. To pursue these interests I will use a variety of biochemical and genetic assays in the highly genetically amenable model organism, Drosophila melanogaster.Given that tissue homeostasis and repair supported by adult SCs is a primordial mechanism of multicellular animals, I anticipate the functional importance of many of the genes to be identified will be conserved between flies and mammals. Understanding the mechanistic basis of adult SC self-renewal, as well as of regulating the differentiation and proliferation of their progeny, will ultimately facilitate stem cell based therapies for regenerative medicine including age-onset diseases and cancer.