Diet promotes muscle stem cell activation and proliferation in Drsosophila - Project Summary Muscle stem cells (MuSCs) are critical for neonatal muscle growth, and repair during aging and muscle disease. These stem cells reside in the vicinity of muscle fibers and stay quiescent under normal conditions. Following muscle damage due to aging or myopathy these stem cells exit quiescence/undergo activation and proliferation, to repair the muscle. Defects in MuSC activation and proliferation triggers muscle degeneration in Duchene muscular dystrophy (DMD), the most common and severe form of muscle disease diagnosed in infants. Impaired MuSC proliferation is also associated with sarcopenia; an age associated loss of muscle mass and strength. Thus, MuSC activation and amplification are critical for its regenerative potential and muscle health. Human clinical studies have highlighted the role of diet in muscle stem cell mediated muscle repair. However, the mechanism through which this regulation takes place is not clearly understood. In this proposal, we decipher the mechanism through which diet or diet responsive PI3K/Akt/Tor signaling promotes muscle stem cell activation and proliferation. Our central hypothesis is that diet positively regulates MuSC activation and proliferation, and this is achieved through the crosstalk between fat body, wing disc niche (MuSC microenvironment) and MuSC. We will test our hypothesis in the following specific aims. Aim 1: Determine how the disruption of PI3K/Akt/Tor signaling in MuSC reduces MuSC pool, muscle growth and function. Aim 2: Decipher the mechanism through which amino acid free diet inhibits MuSC activation and proliferation. Aim 3: Dissect the signaling network that interacts with Akt to amplify MuSC pool and muscle size. The results of this study will provide new insights likely relevant to understand how diet influences MuSC activation/proliferation to promote muscle growth and regeneration during aging and muscle disease in mammals. Our proposed study will identify key components/pathways that may have a role in muscle repair during aging. The SuRE-First grant will provide the required resources and training to approximately 36 undergraduates and 8 graduate students including students from underrepresented minority backgrounds at San Jose State University. The proposed research is student-centered and designed to train students at various educational levels. Most of the proposed study will be performed by undergraduate students under the supervision of the graduate students and PI. The trained senior undergraduate students in the laboratory will train new students, creating a mentoring and learning model that will be implemented for current and future students. This funding will help the PI to continue working towards solving the important scientific problem that impacts human health, provide valuable research training to the students and contribute to the learning environment at San Jose State University.
