Grant: Discovery Grants Program - Individual

Skeletal muscle possesses a wide variety of cell populations that are important for maintaining muscle quality and quantity. Recently, a population of cells that supports muscle regrowth following damage and help prevent muscle loss has been identified. These cells, called fibro/adipogenic progenitors (FAPs) perform these functions by communicating with other cells in muscle and providing instructions on how these other cells should respond to repair damaged muscle. Recent discoveries have determined that FAPs are a diverse mixture of cells with different subgroups each performing unique functions. Some of these subgroups promote muscle repair while others are involved in muscle damage and dysfunction. While most of the research on FAPs has been conducted in the context of muscle repair and in muscle disease, an interesting unanswered question in the field is: "How do FAPs contribute to muscle growth?" The proposed research will begin to answer this question by completing the following three objectives: (1)Determine if FAPs are necessary for muscle growth. To achieve this objective, we will remove FAPs from growing muscle to determine if muscle without FAPs can grow to the same extent as muscle with a normal amount of FAPs. (2)Characterize the different FAP subgroups during muscle hypertrophy. To achieve this objective, we will label FAPs in a manner that allows us to trace their different identities in skeletal muscle. We will then investigate how these subgroups change over time as muscle is growing. (3)Identify how FAPs communicate with other cells in the muscle during muscle growth. To achieve this objective, we will use the same labelled FAPs as in objective 2 and identify which communication factors, these labelled FAPs are using to instruct other cells in muscle to enhance muscle growth. We expect our results to identify which subgroups of FAPs are involved in muscle growth and how they contribute to this process. This new information is important to individuals interested in developing novel interventions to enhance skeletal muscle growth and for those who want to use physiological mechanisms to alter cell fate. Trainees who complete this work will gain valuable skills across several scientific fields and improve their ability to present their work in oral and written formats.