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Analysis of the role of Hypoxia Inducibe Factor pathway in radioprotection


Department of Biomedical Science

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Dr F Van Eeden Applications accepted all year round Self-Funded PhD Students Only

About the Project

Hypoxia inducible factor (HIF) is highly important in human health and disease, as is testified by the 2019 Nobel prize for Medicine or Physiology. We have found a surprisingly strong cytoprotective effect of HIF signalling after treatment of embryos with radiation of other DNA damaging compound, this response is not a trivial ""protection from hypoxic damage"" as might be expected. The response is so strong that embryos with activated HIF survive doses of radiation that are absolutely lethal to normal embryos. HIF active embryos are in that respect similar but not identical to P53 deficient animals.
We have observed effects of HIF activation on P53 activity but we have also data that shows that HIF does more than just blocking P53 function. We want to understand the interaction between these two crucial tumor regulating proteins better. These genes have been extensively researched in cell culture, but often such cultured cells are tumour derived and culture-adapted and do not represent the normal organism well. Therefore, we plan to study their interaction in vivo, using a genetic approach in the zebrafish model system. Using existing mutants and CRISPR to create new ones we want to clarify the precise interactions between these proteins in live embryos using tools that we have established recently. The project will also use advanced imaging (light sheet), fluorescent assays/transgenic, IHC, ISH methods to dissect precise interactions.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit www.sheffield.ac.uk/sgs to learn more.

Funding Notes

This position is open to self-funded students and also has the possibility of being funded by a fees scholarship, further details can be found here: https://www.sheffield.ac.uk/postgraduate/phd/scholarships/faculty

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/postgraduate/research/apply/applying

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.

References

Reference: Kim et al., 2020 bioRxiv 767459; doi: https://doi.org/10.1101/767459
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