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WR DTP project: From single molecules to single cells: Understanding blood stem cell fate choice


Department of Biology

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Dr D G Kent , Prof I Hitchcock No more applications being accepted Competition Funded PhD Project (Students Worldwide)
York United Kingdom Biochemistry Bioinformatics Biomedical Engineering Biophysics Cell Biology Immunology Medical Physics Molecular Biology

About the Project

Haematopoiesis is a complex and finely-tuned process that produces trillions of new blood cells on a daily basis. Adult haematopoietic stem cells (HSCs) are responsible for the lifelong maintenance of this system, making it essential to understand their biology. The balance between mature cell production and HSC maintenance is primarily controlled by cytokines binding to receptors on HSCs and activating downstream signaling pathways. Our recent discovery that cytokine receptor activation is more complex and diverse than previously thought leads to significantly more flexibility and diversity in fate choice probabilities (Wilmes et al., Science 2020). This potentially explains how some cytokines (e.g., SCF, TPO) can simultaneously support HSC maintenance and drive mature blood cell production . This project focuses on the biological mechanism of cytokine:receptor interaction in HSCs, informing efforts to modulate blood cell production and to produce vast quantities of HSCs outside the body.

Novelty
This project will take a novel interdisciplinary approach to understand the fundamental mechanism of how cytokine receptors modulate HSC fate choice. It studies single molecules in single HSCs, leveraging new technologies/approaches in quantitative and biophysical biology, applying them to functionally defined mouse and human HSCs.

Timeliness
Current funded research provides expertise in biophysics and bioengineering in addition to core strengths in HSC biology (Kent) and cytokine signaling (Hitchcock). Both the Kent and Hitchcock groups have a strong track record of successful interdisciplinary projects, applying new technologies to address fundamental biological questions in HSC biology (Nature, 2018) and cytokine receptor signaling (Science, 2020). The labs are funded by the ERC, MRC, CRUK, Blood Cancer UK, and the Bill and Melinda Gates Foundation.

Experimental Approaches
The project involves cellular and molecular characterisation of HSCs. Techniques will include stem cell transplantation, flow cytometry, RNA-sequencing and super-resolution single molecule microscopy.

The White Rose DTP in Mechanistic Biology is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Funding Notes

This project is part of the BBSRC WR DTP in Mechanistic Biology. Appointed candidates will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,285 for 2020/21)
UK tuition fees (£4,473 for 2021/22)
Research support and training charges (RSTC)
We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

ENTRY REQUIREMENTS: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. If English is not your first language, you will need to meet the minimum entry requirements for your country. Please check our website: https://www.york.ac.uk/study/postgraduate-research/apply/international/english/

START DATE: 1st October 2021
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