Research Assistant/Associate to study hypoxia signalling in sympathoadrenal development, based at the University of Cambridge

Applications are invited to recruit an enthusiastic Research Assistant or Research Associate to work on a Wellcome funded project with Dr Emma Hodson (Wellcome Career Development Fellow), in the group of Prof James Nathan (Wellcome Senior Fellow). We are interested in how oxygen availability regulates normal development, specifically, how Hypoxia-inducible factor 2 (HIF-2), an oxygen-sensitive transcription factor, regulates the development of sympathoadrenal and other neural crest-derived neuroendocrine cells. HIF-2 signalling is implicated in the normal physiology of a population of these cells involved in arterial oxygen chemosensitivity (eg the carotid body) but also with sympathoadrenal tumours (pheochromocytoma/ paraganglioma), which are associated with heritable HIF-2 activating mutations. Together, the data suggest a fundamental role for HIF-2 in normal sympathoadrenal development, which has yet to be characterised, but has implications for understanding how the developmental environment (eg hypoxia) programmes the origins of adult disease. We seek to understand whether HIF-2 acts as a lineage specifier in sympathoadrenal cells and how it may programme the differentiation of oxygen-sensitive chemoreceptor cells and/or abnormal tumour pre-cursor cells.

The project will use an established protocol for in vitro sympathoadrenal differentiation to study how hypoxia affects development; characterising the stages most susceptible, the nature of abnormally differentiated cells and the component attributable to HIF-2. The successful applicant will perform in vitro differentiation of human iPSCs/ ESCs into sympathoadrenal cells and assess the effect of culture in graded hypoxia or genetic activation of HIF signalling. We have established reporter cell lines with inducible expression of activated HIF-2, which will allow us to assess the effects of HIF-2 signalling at each stage of sympathoadrenal differentiation from neural crest to differentiated neuroendocrine cells and sympathetic neurons. The work will also assess how hypoxia and/or HIF-2 activation affect the in vivo differentiation and migration of these cells using parallel experiments in the chicken embryo, where multiplexed in-situ hybridisation assays are already developed.

The post will be based in James Nathan’s laboratory in the Jeffrey Cheah Biomedical Centre, incorporating CIITID and the Cambridge Stem Cell institute, on the Cambridge Biomedical Campus. The project also involves collaborations with groups at the Department of Physiology, Development and Neuroscience (Cambridge University) and the Francis Crick Institute (London). Together, the team incorporates clinician scientists and academics with extensive expertise in developmental biology, hypoxia signalling and autonomic function.

Applicants should have a primary degree in biomedical sciences and a PhD. Those without a PhD may also be considered as a research assistant. Experience with cell culture and molecular biology is required. Experience with iPSC/hESC maintenance and differentiation, and/or chicken embryo work is desirable but not essential.

Closing Date: 6th August 2023

Interview Date: to be confirmed

Fixed-term: The funds for this post are available until 31 January 2025 in the first instance.

https://www.jobs.cam.ac.uk/job/41888/