2023 Collagen Gordon Research Conference and Seminar

2023年胶原蛋白戈登研究会议暨研讨会

• 批准号: 10675849
• 负责人: Douglas Gould
• 金额: $ 2.9万
• 依托单位: GORDON RESEARCH CONFERENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10675849
• 关键词: Affect; Anabolism; Award; Big Data; Binding; Biochemical; Biological Process; Biology; Biomechanics; Biomedical Engineering; COVID-19 pandemic; Cell physiology; Cells; Characteristics; Chronic; Code; Collagen; Collagen Gene; Communities; Complex; Counseling; Cues; Data; Defect; Dependence; Development; Developmental Process; Disease; Drug Targeting; Endowment; Enzymes; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Functional disorder; Future; Genes; Genetic; Goals; Growth; Growth and Development function; Health; Hearing; Homeostasis; Human; Human body; Hydroxylation; Hypoxia; Hypoxia Inducible Factor; Invertebrates; Kidney Diseases; Knowledge; Link; Malignant - descriptor; Medicine; Modification; Molecular; Musculoskeletal Development; Mutate; Mutation; Nobel Prize; Organ; Organism; Organogenesis; Oxygen; Parents; Pathogenesis; Pathologic; Pathology; Physiological; Physiology; Post-Translational Protein Processing; Process; Procollagen-Proline Dioxygenase; Proline; Property; Protein Family; Proteins; Proteolysis; Renal carcinoma; Research; Research Personnel; Role; Science; Scientist; Series; Stimulus; Structure; Students; Systems Biology; Tissues; Translating; Vertebrates; angiogenesis; career; cell growth regulation; collaborative environment; extracellular; frontier; gene product; meetings; mutant; novel; novel therapeutic intervention; pleiotropism; resilience; response; stem cell function; stem cell niche; stem cells; symposium; triple helix; unpublished works; virtual

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.

项目摘要 胶原蛋白是通常在细胞外基质（ECM）中形成分子聚集体的大分子。 脊椎动物中有28种不同的胶原蛋白，它们都由3条胶原蛋白链组成，折叠成一条或多条 特征性三螺旋结构域。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形成的异源三聚体：因此，46个基因编码胶原蛋白。 在人类身上。此外，几种其他分子含有胶原结构域。发病机制可能是由于 蛋白质的量不足或存在突变形式，并且几乎可以影响所有组织 和器官。组织脆性，通常是胶原蛋白功能障碍的标志，以及纤维化过程，即积聚 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。 传统上认为胶原蛋白为组织提供结构支持。现在很清楚，他们 具有由母体分子或亚结构域执行的其它重要生物学功能， 通过蛋白水解释放并赋予其新的生物活性。这些可变但关键的功能 包括在控制血管生成、干细胞壁龛和恶性生长中的作用。胶原蛋白功能也可以 通过异常复杂的翻译后修饰，例如4-羟基化， 脯氨酸残基。有趣的是，机制上类似的酶被用来调节身体的缺氧 这是2019年诺贝尔医学和生理学奖授予的一项发现。 2023年的会议将标志着胶原蛋白GRCs的50多年，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 在生理环境中与其他ECM分子和细胞相互作用， 这些复杂的相互作用和依赖性的胶原突变的后果。 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，例如最近的 了解到现在可以用来开发针对缺氧诱导因子（HIF）脯氨酰的药物， 用于治疗，例如，慢性肾病和癌症。其他影响力日益增强的领域 将突出涉及生物力学和生物工程方面，干细胞指导，纤维化， 恶性生长以及肌肉骨骼发育和病理学。胶原蛋白大数据会议 研究旨在提出快速增长的系统生物学方法， 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的新数据， 以及组织和细胞中胶原蛋白的稳态。会议还将提供一个独特的机会， 讨论这个快速发展的领域在5-10年内的发展情况，以及该领域需要什么来推进。 2019冠状病毒病疫情导致的四年中断进一步凸显了二零二三年的重要性 会议和研讨会都建立了科学家，特别是早期的职业研究人员。