2023 Collagen Gordon Research Conference and Seminar

项目总结

Project Summary Collagens are large molecules that typically form molecular aggregates in the extracellular matrix (ECM). There are 28 distinct collagens in vertebrates, all composed of 3 collagen chains that fold into one or more characteristic triple helical domain. Some collagens are homotrimers formed of three identical chains and others are heterotrimers formed of two or three distinct gene products: hence, 46 genes code for the collagens in humans. In addition, several other molecules contain collagenous domains. Pathogenesis can result from either insufficient amount or the presence of mutant forms of the protein and can affect virtually all tissues and organs. Tissue fragility, often a sign of collagen dysfunction, and fibrotic processes, that is accumulation of collagen, are classical examples of how collagen defects or dysregulation affect health and disease. Collagens are traditionally recognized for providing structural support for tissues. It is now clear that they have other important biological functions that are executed by the parent molecule or by subdomains that are proteolytically released and endowed with novel bioactive properties. These variable, yet critical, functions include roles in controlling angiogenesis, stem cell niches, and malignant growth. Collagen function can also be variably tuned through unusually complex posttranslational modifications, exemplified by 4-hydroxylation of proline residues. Interestingly, mechanistically similar enzymes are used to regulate the body´s hypoxia response, a finding awarded by the 2019 Nobel Prize in Medicine and Physiology. The 2023 meeting will mark over 50 years of the Collagen GRCs, an uninterrupted series starting in 1970, and since 2013 expanded to include a GRS targeting ECRs. The central goal is to understand how collagens interact with other ECM molecules and cells in physiological contexts, and what are the molecular consequences of collagen mutations with respect to these complex interactions and dependencies. Importantly, we will link collagen research to a broader context of biology, as exemplified by the recent understanding that can now be used to develop drugs that target the hypoxia inducible factor (HIF) prolyl- hydroxylases for the treatment of, e.g., chronic kidney disorders and cancer. Other fields growing in impact that will be highlighted pertain to biomechanical and bioengineering aspects, stem cell guidance, fibrosis, malignant growth, and musculoskeletal development and pathology. The session on big data in collagen research aim to bring forward the rapidly increasing systems biology approach regarding the association and roles of collagens in normal and disease situations. Moreover, we aim to highlight novel data on the transport and homeostasis of collagens in tissues and cells. The meeting will also provide a unique opportunity to discuss how the rapidly expanding field will look in 5-10 years and what is needed for the field to advance. The break of 4 years induced by the Covid 19 pandemic further highlights the importance of the 2023 conference and seminar both for established scientists and especially the early career researchers.