Role of chromatin fiber structure in genome function

基因组被限制在真核细胞的微小的微米大小的细胞核中，在那里它们被高度压缩，同时不断地被解释基因组信息以产生细胞所需的构建模块的细胞机器访问。在细胞分裂过程中，基因组需要快速而完全地复制和分离。这些非凡的特征高度依赖于基因组的三维结构及其包装材料染色质。我们知道，DNA包裹成核小体，基因组组织的基本单位，对所有核过程有很大的影响。此外，基因组区域之间的长程相互作用正变得越来越好理解，并且在复杂的调控途径中特别重要。了解基因组在三维空间中的功能对于理解细胞如何适应环境、多细胞生物如何发育以及理解导致疾病的机制至关重要。该建议旨在阐明在基因组背景下核小体如何在染色质纤维内结构化以及这种折叠如何涉及基因组功能的知之甚少的领域。申请人因其对染色质纤维折叠的理解而享誉世界。他的团队将与基因组学应用方面的国际合作者一起，使用最新一代的基因组学和遗传学方法来建立新的工具，以扩展我们理解真核基因组结构和功能的能力。

Genomes are confined in the tiny, micrometer sized nuclei of eukaryotic cells, where they are highly compacted and at the same time constantly accessed by the cellular machinery that interprets the genomic information to produce the building blocks that the cell needs. During cellular division, the genome needs to duplicate and segregate rapidly and completely. These extraordinary features highly depend on the three-dimensional structure of the genome and on its packaging material called chromatin. We know that the wrapping of DNA into nucleosomes, the basic units of genome organization, has a great impact on all nuclear processes. Also long-range interaction between genomic regions are becoming better and better understood, and are particularly important in complex pathways of regulation. Knowing how the genome functions in a three-dimensional space is crucial for understanding how cells adapt to the environment, how multi-cellular organisms develop and for understanding the mechanisms causing disease. This proposal aims at elucidating the poorly understood area of how nucleosomes are structured inside the chromatin fiber in a genomic context and how this folding is implicated in genome function. The applicant is world-renowned for his track record on understanding chromatin fiber folding. Together with international collaborators who are experts in genomic applications, his team will use the latest generation methods of genomics and genetics to establish new tools that extend our capabilities of understanding the structure and function of eukaryotic genomes.