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Development of the hematopoietic/ immune system in the embryo

Weatherall Institute of Molecular Medicine

Prof M DeBruijn Friday, July 23, 2021 Self-Funded PhD Students Only
Oxford United Kingdom Cell Biology Immunology Medicine

About the Project

Our aim is to obtain a mechanistic insight into the birth of hematopoietic stem and progenitor cells in embryonic development and determine the contribution of these cells to the emerging hematopoietic and immune systems of the embryo.

Hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and adaptive immune cells. They are generated de novo early in development from a specialized subset of endothelial cells, the so-called hemogenic endothelium (HE). Prior to HSC generation, the embryo produces hematopoietic progenitor cells that support its growth and development and contribute to tissue-resident innate immune cells. Taking advantage of unique Runx1 enhancer-reporter mouse models generated in our laboratory we set out to dissect the cellular and molecular events that underlie the birth of blood stem and progenitor cells. Using one of these models we previously analysed HE at the single cell level, showing its dynamic nature during mouse development and rewriting the time line for HE specification to the hematopoietic lineage (Swiers et al., Nature Communications 2013). More recently, we have performed extensive expression (RNA-seq) and chromatin (ATAC-seq) profiling of Runx1 enhancer-reporter-marked cells throughout early mouse development to construct gene interacting networks and identify new players critical to the formation of HE and hematopoietic stem and progenitor cell lineages that will be tested experimentally. Another line of work in the laboratory aims to trace the early mesodermal origin(s) of hematopoietic stem cells and specific progenitors in the mammalian embryo to map their trajectories through the embryo and the signals they receive that affect their fate decisions. Altogether, insights obtained from these studies will contribute to a better understanding of the cell types that build and maintain the adult hematopoietic and immune systems. The signals and gene interacting networks underlying the formation of these cells will inform the future directed differentiation of ESC/iPSC into clinically relevant hematopoietic and/or immune cells.

Our laboratory is now looking for enthusiastic and motivated students to join our team. The successful candidate will be part of the Developmental Hematopoiesis group in the MRC Molecular Haematology Unit of the MRC Weatherall Institute of Molecular Medicine (WIMM) at the Radcliffe Department of Medicine. In pursuing her/his project, the candidate will have ample opportunities for collaboration with other groups in the WIMM and the Radcliffe Department of Medicine working on gene regulation and epigenetics, gene editing, blood stem and progenitor cell biology, and computational biology. There is an active student association in the WIMM, which organises several events throughout the year.

For further information on potential project areas, please contact:
Prof Marella de Bruijn

Funding Notes

Funding for this project is available to scientists through the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.

For October 2021 entry, the application deadline is 8th January 2021 at 12 noon midday, UK time.

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