Project description DEENESFRITPL Understanding what makes cells change their identity Our cells carry the code for all the proteins our body makes. However, each cell type makes only those proteins required for its function. During normal development or abnormal processes such as cancer, a cell changes its identity during cell division. At this time, chromatin condenses, copies of the code are made, and they are passed on to the daughter cells. The window between chromatin condensation and chromatin reorganisation represents an important opportunity for reprogramming. The RepDiff project plans to compare proteins in undifferentiated cells that remain pluripotent after cell division with those in cells that take on new identities. Insight will have broad-reaching impact on normal and abnormal cell fate transitions. Show the project objective Hide the project objective Objective All cells in our body share the same genetic information. Cellular identity is determined by epigenetic mechanisms, which control gene expression. Replicating cells should accurately replicate their DNA sequence and copy their epigenetic profile to maintain their identity. DNA replication entails the disruption of the chromatin organization ahead of the replication fork and its restoration behind it. When cells change their identity in either normal development or abnormal processes as cancer, they undergo epigenetic reconfiguration, which defines their new identity. Recent works have revealed a time gap between DNA replication and epigenetic state restoration of many chromatin regulation layers. I hypothesize that the time until chromatin restoration post DNA replication provides a ‘window of opportunity’ for transcription factors and chromatin regulators to bind otherwise inaccessible areas and to facilitate chromatin reconfiguration and that pluripotent cells have specialized chromatin replication proteins, which preserve their high epigenetic plasticity. To test this hypothesis, I will join the lab of Prof. Anja Groth, a leading expert in the mechanisms controlling chromatin replication. Together with my expertise in stem cells and reprogramming, I will address this question with two sequential steps. I will use a cutting edge, quantitative proteomics method in which nascent DNA is affinity purified and its associated proteins are analyzed by mass-spectrometry (NCC-SILAC). I will use this discovery tool to define the proteins dynamically associated with nascent chromatin in pluripotent cells and cells that undergo cell fate transitions. I will then investigate proteins predicted to effect chromatin restoration/reconfiguration to dissect their functional role. This work has the potential to reveal a mechanistic link between DNA replication and cell fate decision and thus significantly contribute to the fields of development, stem cells, and cancer. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator KOBENHAVNS UNIVERSITET Net EU contribution € 219 312,00 Address Norregade 10 1165 Kobenhavn Denmark See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
