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EASTBIO In vitro modelling of the embryonic haematopoietic stem cell niche


   School of Biological Sciences

  Prof A Medvinsky, Dr G Blin  Monday, December 05, 2022  Competition Funded PhD Project (Students Worldwide)

About the Project

Background. The first haematopoietic stem cells (HSCs) emerge in the embryonic aorta-gonad-mesonephros (AGM) region through a process called endothelial-to-haematopoietic transition (EHT). We previously showed that secreted molecules in the AGM region are spatially polarized and some of them support HSC development (2,3). However, the full impact of this complex polarized microenvironment on haematopoietic development remains unclear. We propose that spatial intersections of secreted factors define the efficacy and specifics of EHT within the AGM region.

Objectives. We will investigate how spatial patterning of secreted molecules in the AGM region impacts on haematopoietic development (EHT). Using human ES cells, we will model the HSC niche by spatially patterned combinatorial expression of secreted molecules. Results will be obtained and analysed using fluorescent reporters, single cell RNAseq, flow cytometry and computer modelling. In the longer term, these analyses will facilitate generation of human HSCs for clinical needs.

Techniques and skills to be employed/ acquired. This project will be carried out in a highly collaborative environment. The student will learn cutting-edge and multidisciplinary methods including human ES cell differentiation, live imaging, micropatterning, confocal microscopy, flow cytometry, CRISPR/Cas9 gene editing; gene expression profiling (RNAseq) and bioinformatics. 

The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity

The “Institution Website” button will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate (£17,668 annually in 2022) and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants, however any Visa or Health Insurance costs are not covered. UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

References

1. Ivanovs, A., Rybtsov, S., Ng, E.S., Stanley, E.G., Elefanty, A.G., and Medvinsky, A. (2017). Human haematopoietic stem cell development: from the embryo to the dish. Development 144, 2323-2337. 2. Crosse, et al (2020). Multi-layered spatial transcriptomics identify secretory factors promoting human hematopoietic stem cell development. Cell Stem Cell 27, 822-839.
3. Souilhol, et al (2016) “Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells. Nat. Commun. 7, 10784.

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