Role of chromatin fiber structure in genome function

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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.