Proteolysis is a critical post-translational modification as every protein encounter a protease in their lifetime, be it signal peptide removal, activation, processing, or degradation. Proteases act in concerted networks to amplify signals, regulate biology and are hypothesized molecular switches and effectors involved in tissue remodeling. The extracellular matrix (ECM) regulates key functions such as cell movement, shape, growth and survival via cell adhesion, cell-ECM, and cell-cell interactions. The ECM is a non-cellular structure that is highly dynamic and remains in close contact with cells either throughout their entire life or at important phases of their development. For this reason, the ECM is present in all tissues and organs of the body, providing structural support as one of its main functions. However, the ECM plays additional biological functions that are still uncharacterized. We are only beginning to understand the intriguing regulatory aspects of proteases that modulate the ECM dynamic remodeling; but many questions remain. Specifically, 1- How universal are the auto-feedback mechanisms driven by ECM proteolysis? 2- How does cleaved ECM regulate the initiation and resolution of inflammation and cancer progression? 3- Does aberrant proteolysis dysregulate the resolution of inflammation or it is the ECM that regulate proteolysis?
Our meeting will directly address these questions by inviting several experts from the ECM and proteases and give them an opportunity to discuss where the next decade will take us. We will also discuss advanced system-biology experimental and computational tools designed to characterise ECM-protease multi-factorial proteolytic cascades and networks in health and disease.
