Conference: Gordon Research Conference in Centromere Biology

会议：戈登着丝粒生物学研究会议

• 批准号: 2201104
• 负责人: Iain Cheeseman
• 金额: $ 1.75万
• 依托单位: Whitehead Institute for Biomedical Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2201104&HistoricalAwards=false
• 关键词: Conference; Gordon; Research; Centromere; Biology

Centromeres remain perhaps the most enigmatic regions of the eukaryotic genome, despite their critical role as the foundation for chromosome segregation during every eukaryotic cell division. The importance of centromeres in genome inheritance has long been recognized, but their properties, organization, and variability have remained mysterious. Indeed, despite the “complete sequencing” of the human genome more than a decade ago, it was only recently that the first assembly of a human centromere was completed. This advance is now allowing researchers to harness this sequence information to tackle fundamental questions on centromere properties and behavior. The proposed Gordon Research Seminar and Conference will stimulate discussions to consider how the field will need to build upon centromere DNA sequence information towards understanding the increasing complexity in structure and function. This conference will act as an important catalyst for the centromere field to generate a unique conceptual framework to address these questions, together with tools and technologies that combine genome, computational and bioinformatics approaches, and complementary functional biological studies at the molecular, cellular, and organismal levels. The Broader Impacts of effort include the intrinsic merit of the research as all eukaryotic cells rely on centromeres during cell division. In addition, training and networking opportunities will be provided for the next generation of researchers. Proper centromere function requires a complex cascade of biochemical events to direct chromatin and kinetochore assembly and involves hundreds of different proteins. However, the precise mechanisms that integrate the genetic and biochemical events leading to functional centromeres are still largely unknown. Kinetochore formation during mitosis depends upon the specialized centromeric chromatin in which histone H3 nucleosomes are replaced with nucleosomes containing the centromeric histone Centromere Protein A (CENP-A). Failure to load CENP-A into centromeres each cell cycle ultimately leads to centromere loss, kinetochore failure, chromosome mis-segregation and cell death. Defects in centromere function and the resulting chromosome segregation errors lead to chromosome aneuploidy, a hallmark of many afflictions. Over the past decade, centromere researchers have identified some of the key factors that control centromere protein assembly and the epigenetic maintenance of centromeric chromatin. However, we lack a clear understanding of how these factors come together to generate centromeres at a specific locus through each cell division cycle and this conference and associated seminar will bring together researchers to discuss strategic directions that are needed to advance our understanding of this important region of the genome.This conference is co-sponsored by the Cellular Dynamics and Function together with the Genetic Mechanisms program, both within the Division of Molecular and Cellular BiosciencesThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

着丝粒可能仍然是真核生物基因组中最神秘的区域，尽管它们在每一次真核细胞分裂中作为染色体分离的基础发挥着关键作用。着丝粒在基因组遗传中的重要性早已被认识到，但它们的性质、组织和变异性仍然是个谜。事实上，尽管人类基因组的“完全测序”在十多年前就完成了，但直到最近才完成了人类着丝粒的首次组装。这一进展现在使研究人员能够利用这些序列信息来解决着丝粒特性和行为的基本问题。拟议的戈登研究研讨会和会议将激发讨论，考虑该领域将如何需要建立在着丝粒DNA序列信息的基础上，以了解结构和功能日益复杂的问题。这次会议将作为一个重要的催化剂，为着丝粒领域产生一个独特的概念框架，以解决这些问题，连同工具和技术，结合联合收割机基因组，计算和生物信息学方法，并在分子，细胞和生物体水平的互补功能生物学研究。努力的更广泛影响包括研究的内在价值，因为所有真核细胞在细胞分裂期间都依赖于着丝粒。此外，还将为下一代研究人员提供培训和建立联系的机会。正确的着丝粒功能需要一系列复杂的生化事件来指导染色质和动粒组装，涉及数百种不同的蛋白质。然而，整合遗传和生物化学事件导致功能性着丝粒的精确机制在很大程度上仍然未知。有丝分裂期间动粒的形成取决于特化的着丝粒染色质，其中组蛋白H3核小体被含有着丝粒组蛋白着丝粒蛋白A（CENP-A）的核小体取代。每个细胞周期未能将CENP-A加载到着丝粒中最终导致着丝粒丢失、动粒失效、染色体错误分离和细胞死亡。着丝粒功能的缺陷和由此产生的染色体分离错误导致染色体非整倍性，这是许多疾病的标志。在过去的十年中，着丝粒研究人员已经确定了一些控制着丝粒蛋白组装和着丝粒染色质表观遗传维持的关键因素。然而，我们缺乏对这些因素如何在每个细胞分裂周期中共同在特定位点产生着丝粒的清晰理解，本次会议和相关研讨会将汇集研究人员讨论推进我们对基因组这一重要区域的理解所需的战略方向。本次会议由细胞动力学和功能与遗传机制计划共同主办，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。