Novel tools for modelling normal and perturbed haematopoiesis

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Blood cell production (haematopoiesis) is a finely tuned process, producing trillions of new blood cells daily. Dysregulation leads to a wide array of haematological diseases including bone marrow failure and leukaemia. Despite generating detailed molecular profiles of individual blood forming cells at unprecedented resolution and comprehensively mapping genetic drivers in numerous haematological diseases, we lack effective tools to map and manipulate key cellular subsets involved in normal and stressed haematopoiesis which would provide fundamental insight into disease aetiology and potential intervention strategies.Our cluster of world-leading experts in developmental and malignant haematopoiesis, the haematopoietic niche, and oligogenic mouse modelling will develop new tools to revolutionise how we study and manipulate haematopoietic/immune-cell function for clinical benefit. Building on our extensive clinical and molecular datasets from normal, post-infection and pre-leukaemic and leukaemic cells, we will develop new tools to precisely map and manipulate haematopoietic cells. These approaches will support fundamental breakthroughs in haematopoiesis and facilitate production of new models with genetic manipulations restricted to highly defined cell populations with temporal regulation. This collaborative network will also involve cross-institutional model-sharing and standardisation, and catalyse disease model development in other fields.