Objectif The research programme will comprise the study of the Histone acetyl transferase (HAT) MOZ (Monocytic leukaemia Zinc finger) a critical player in the development and maintenance of the haematopoietic system. In addition, translocations of MOZ are associated with Acute Myeloblastic Leukaemia. Given the importance of this protein in haematopoiesis and leukaemogenesis, it would be essential to further understand the function of MOZ and in particular to identify the genes regulated by its HAT activity of MOZ. A mouse line specifically mutated to abrogate the HAT enzymatic activity of MOZ has been developed in the host laboratory, and represents a powerful and unique tool for the study of MOZ HAT activity. Using Chromatin ImmunoPrecipitation followed by sequencing (ChIP-seq), genome wide targets of MOZ will be determined and the consequences of the deletion of its HAT activity on the epigenetic landscape will be investigated through the survey of several histone modifications and RNA polymerase II recruitment. The non-histone targets of MOZ will be identified through the SILAC technique. Finally a MOZ murine leukaemic model has been developed, based on the transduction of bone marrow cells with a retrovirus encoding MOZ-TIF2, one of the fusion proteins involving MOZ. ChIP-seq will be performed in these leukaemic cells to identify genes targeted by MOZ-TIF2 and changes in epigenetic marks at these loci. Overall, this project will provide a better understanding of MOZ HAT activity in haematopoiesis and leukaemogenesis. Crucially, this project will enable Dr Anne Largeot to obtain and develop a wide range of new and transferable skills through a variety of multidisciplinary training programs. Relying on the knowledge and expertise of her supervisor and the exceptionally high calibre of the Cancer Research UK Manchester Institute, this project will enable Dr Anne Largeot to achieve her long-term objective of obtaining a leadership position in a competitive European Institute Champ scientifique natural sciencesbiological sciencesgeneticsDNAnatural scienceschemical sciencesinorganic chemistrytransition metalsnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologyleukemia 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 Thème(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-ST - Standard EF Coordinateur THE UNIVERSITY OF MANCHESTER Contribution nette de l'UE € 195 454,80 Adresse OXFORD ROAD M13 9PL Manchester Royaume-Uni Voir sur la carte Région North West (England) Greater Manchester Manchester Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 195 454,80
