Investigating the Skeletal Muscle Secretome and its Role in Cardiometabolic Disease: Developing a Novel 3D Model of Muscle Contraction (360G-Wellcome-217055_Z_19_Z)

It is now abundantly clear that skeletal muscle has extraordinary endocrine and metabolic functions that extend far beyond a simple role in energy utilisation during exercise. Contracting skeletal muscle is capable of producing unique secretory signatures that can influence both proximal and distal tissues to influence metabolic activity in the pathogenesis of obesity- related disease. Detailed investigation of skeletal muscle biochemistry, secretory activity and potential cross-talk with other metabolic tissues (including liver and adipose as major metabolic organs involved in glucose regulation linked to T2D) requires robust in vitro models of muscle contraction which to date have proven elusive. This project proposes to develop and validate a novel 3D model of skeletal muscle contraction for utilisation in future studies which will identify specific myokine profiles and investigate their role in cardiometabolic disease. Ultimately this will enable us to enhance target myokine secretion, and their crosstalk with other tissues, as a therapy to improve metabolism and key features of type 2 diabetes.