Department of Biological Sciences Pedro Granados Mentor ...

Department of Biological Sciences Pedro Granados Mentor: Matthew Wallenfang Role of a pro-aging gene on germline stem cell function in Drosophila melanogaster Stem cells are cells with the defining ability to be able to give rise to one or more types of differentiated progeny, while also undergoing self-renewing divisions that give rise to undifferentiated stem cells identical to the mother stem cell. Adult stem cells are used to maintain tissue homeostasis in broad range of tissues, including the skin, gut, blood and reproductive organs. Because these adult stem cells persist throughout the lifetime of the organism, they are thought to play a key role in aging. Germline and stem cells (GSCs) in the Drosophila testes, which are used to maintain spermatogenesis, have emerged as an important model for the study of stem cell aging. Much is known about the molecular mechanisms that are used to maintain these stem cells, and more recent studies have begun to describe the changes that occur in these stem cell populations during aging. In particular, it is known that germline stem cells decrease their division rate (Wallenfang et al 2006). Interestingly, this change in division rate is not observed in flies that are mutant for the gene methuselah (mth). Mth mutant flies are significantly longer lived than wild type flies, and thus one role of mth is to promote normal aging. How mth acts at a cellular level remains unknown, and we are using its effects on germline stem cells to investigate this issue. In this project, we are particularly interested in defining in which cells mth acts to promote aging of germline stem cells. Mth may have a role in the GSCs themselves, but might instead be required in the cells adjacent to the GSCs that make up the stem cell niche; these cells would then relay a local signal to the GSCs to promote aging. It is also possible that mth’s role may be somewhere distant from the GSCs, and long-range signaling to GSCs then used to promote aging. To distinguish between these possibilities, this summer we began to construct flies that are mutant for mth in all cells, but then have transgenes to express mth specifically in defined subsets of cells – either the GSCs, the local niche cells of the testis, or in all cells of the fly. Once these strains have been constructed, we will determine the division rate of the stem cells to determine if they are aging normally or if they aging similar to cells in a mth mutant fly. Taken together, these studies will allow us to begin to define how genetic aging programs act at a cellular level.