Obiettivo
Chromatin undergoes fascinating structural and functional changes during the metazoan cell cycle. It massively condenses at the beginning of mitosis with a degree of compaction up to fiftyfold higher than in interphase. At the end of mitosis, mitotic chromosomes decondense to re-establish their interphase chromatin structure. This process is indispensable for reinitiating transcription and treplication, and is thus of central importance in the cellular life cycle. Despite its significance to basic research as well as its potential medical implications, postmitotic chromatin decondensation is only poorly understood. It has been well described cytologically, but we lack an understanding of the underlying molecular events. We are ignorant about the proteins that mediate chromatin decondensation, the distinct steps in this multi-step procedure and their regulation.
Using a novel in vitro assay, which recapitulates the process in the simplicity of a cell free reaction, we will identify the molecular machinery mediating postmitotic chromatin decondensation and define the different steps of the process. The cell free assay offers the unique possibility to isolate and purify activities responsible for individual steps in chromatin decondensation, to identify their molecular composition and to analyse the molecular changes they induce on chromatin. Accompanied by live cell imaging in mammalian tissue culture cells, the proposed approach will not only facilitate the elucidation of the factors involved in chromatin decondensation, but will also provide insight into how this process is integrated into mitotic exit and nuclear reformation and linked to other concomitant processes such as nuclear envelope assembly or nuclear body formation.
Thus, using an unprecedented approach to study the ill-defined but important cell biological process of postmitotic chromatin decondensation, we aim to expand the frontiers in our knowledge on this topic.
Campo scientifico
Invito a presentare proposte
ERC-2012-StG_20111109
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Meccanismo di finanziamento
ERC-SG - ERC Starting GrantIstituzione ospitante
52074 Aachen
Germania