Reprogramming Extracellular Matrix (360G-Wellcome-226804_Z_22_Z)

Extracellular matrix is essential for multicellular life. As a third of body mass, it surrounds cells, defines tissue architecture, and provides instructive signals for diverse cellular processes. Altered matrix is a hallmark of almost all genetic and acquired disorders leading to debilitating tissue degeneration and fibrosis. Major gaps in understanding the normal assembly, maintenance and turnover of matrix have limited disease studies and prevented the development of effective matrix-targeted therapies. Our goal is to identify strategies to reprogramme matrix and thereby prolong tissue health. However, there are key conceptual and technical barriers to understanding how altered matrix leads to tissue decline. By innovating and improving technologies we aim to overcome three important barriers: 1) Resolve matrix in high definition including post-translational modification and physical properties; 2) Create tools to track and manipulate the living matrix to understand turnover and spatial dynamics; and 3) Integrate and model matrix data to predict, test and define the transition from tissue health to decline. We will build capacity and improve access to matrix research in broader scientific and clinical communities. Success will enable early diagnostics to detect loss of matrix regulation and the development of precision strategies for matrix reprogramming across multiple disease aetiologies.