Structure and Cellular Dynamics of the Sarcomere

Muscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, uMuscles are specialized tissues that power voluntary, fast and coordinated movements, a hallmark of animal life. The force-generating and load-bearing devices of muscles are called sarcomeres, highly structured ensembles of many proteins. While many sub-components are structurally and functionally characterised, muscle is more than the sum of these parts: its function is highly cooperative and its structure dynamic over time and space. The high-resolution structure of sarcomeres is unknown, yet a precise molecular understanding of how the entire sarcomere machine forms and functions is required to understand its role in health, disease and ageing. This consortium will deploy an unparalleled complementary knowledge and technology base to address these fundamental and translational questions. We will solve the structure of the sarcomere at near-atomic resolution, unravel the fundamentals of its force-driven assembly and turnover in health and ageing, and develop the foundations for future basic and translational research including the design and development of new agents to mitigate muscle disease and ageing.