Xi’an Jiaotong-Liverpool University Featured PhD Programmes
Peter MacCallum Cancer Centre Featured PhD Programmes

Dissecting the role of novel haematopoietic factors in development and disease


Institute of Cancer and Genomic Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

Blood is made up of different cell types with different functions, such as carrying oxygen (red blood cells), help with wound healing (platelets) and fighting infections (white blood cells). All these cells arise from Haematopoietic stem cells (HSCs) that live in our bone marrow. They are generated during embryonic development, arising from the haemogenic endothelium (HE), a specialized subset of endothelial cells located in the floor of the main embryonic artery, the dorsal aorta. The mechanisms leading first to the emergence of HSC and then to the differentiation to all haematopoietic lineages (e.g. erythrocytes, macrophages, T-cells) are very well conserved in zebrafish. The student will use a combination of classical developmental biology, transgenesis and gene editing, together with (single cell) transcriptional profiling and computational tools to study the role of novel haematopoietic factors and understand how they shape haematopoiesis in embryonic development and in blood malignancies such as leukaemia. This is a collaboration with a bioinformatics lab and ample opportunity for training will be provided. A better understanding of how these factors interact to generate and maintain a healthy haematopoietic system in a whole organism is critical both to design new approaches to generating stem cells in vitro but also to help design effective interventions when haematopoiesis is perturbed in diseases such as leukaemias.

Funding Notes

This project is for self-funded UK/EU or self-funded/government-funded international students.

References

References
Dobrzycki, T., Mahony, C.B., Krecsmarik, M., Koyunlar, C., Rispoli, R., Peulen-Zink, J., Gussinklo, K., Fedlaoui, B., de Pater, E., Patient, R., and Monteiro, R. (2020). Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis. Commun Biol 3, 71.
Bonkhofer, F., Rispoli, R., Pinheiro, P., Krecsmarik, M., Schneider-Swales, J., Tsang, I.H.C., de Bruijn, M., Monteiro, R.*, Peterkin, T., and Patient, R*. (2019). Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium. Nat Commun 10, 3577.
* Corresponding authors
Monteiro, R.*, Pinheiro, P., Joseph, N., Peterkin, T., Koth, J., Repapi, E., Bonkhofer, F., Kirmizitas, A., and Patient, R.* (2016). Transforming Growth Factor beta Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells. Dev Cell 38, 358-370.
* Corresponding authors
Ciau-Uitz, A., Monteiro, R., Kirmizitas, A., and Patient, R. (2014). Developmental hematopoiesis: ontogeny, genetic programming and conservation. Exp Hematol 42, 669-683.


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