2023 Collagen Gordon Research Conference and Seminar

项目摘要 胶原蛋白是大分子，通常在细胞外基质(ECM)中形成分子聚集体。 脊椎动物有28种不同的胶原蛋白，所有胶原蛋白都由3条胶原蛋白链折叠成一条或多条胶原蛋白 典型的三螺旋结构域。一些胶原蛋白是由三条相同的链形成的同源三聚体 其他的是由两个或三个不同的基因产物组成的异源三聚体：因此，有46个基因编码胶原蛋白 在人类身上。此外，其他几个分子含有胶原域。致病原因可能是 蛋白质的数量不足或存在突变形式，几乎可以影响所有组织 和器官。组织脆性，通常是胶原功能障碍的标志，以及纤维化过程，即堆积 胶原蛋白，是胶原蛋白缺陷或失调如何影响健康和疾病的经典例子。 胶原蛋白传统上被认为是为组织提供结构支持。现在很明显，他们 具有其他重要的生物学功能，这些功能是由母分子或由以下亚域执行的 蛋白水解性释放，并被赋予新的生物活性。这些可变但关键的函数 包括在控制血管生成、干细胞定位和恶性生长方面的作用。胶原蛋白功能还可以 通过异常复杂的翻译后修饰进行可变调整，例如4-羟基化 脯氨酸残基的含量。有趣的是，机械上相似的酶被用来调节身体的缺氧。S 2019年诺贝尔医学和生理学奖授予了这一发现。 2023年的会议将标志着胶原蛋白GRC诞生50周年，这是一个从1970年开始的不间断系列， 自2013年以来，扩大到包括针对ECR的GRS。中心目标是了解胶原蛋白是如何 在生理环境中与其他细胞外基质分子和细胞相互作用，分子是什么？ 胶原蛋白突变与这些复杂的相互作用和依赖关系的后果。 重要的是，我们将把胶原蛋白研究与更广泛的生物学背景联系起来，就像最近的 了解到这一点，现在可以用来开发针对缺氧诱导因子(HIF)脯氨基的药物。 用于治疗慢性肾脏疾病和癌症的羟基酶。其他领域的影响越来越大 重点将涉及生物力学和生物工程方面，干细胞指导，纤维化， 恶性生长、肌肉骨骼发育和病理学。关于胶原蛋白大数据的会议 研究目的是提出快速增长的系统生物学方法来研究这种联系和 胶原蛋白在正常和疾病情况下的作用。此外，我们的目标是突出运输方面的新数据 组织和细胞中胶原蛋白的动态平衡。这次会议还将提供一个独特的机会来 讨论快速扩展的领域在5-10年后将是什么样子，以及该领域需要什么才能取得进步。 19型Covid大流行导致的4年中断进一步突显了2023年 会议和研讨会都适用于知名科学家，尤其是职业生涯早期的研究人员。

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.