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SINHCAF, a previously unknown link between HIF and NF-kappaB signalling

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  • Full or part time
    Prof S Rocha
    Prof N Perkins
    Prof C Eyers
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Hypoxia and inflammation are important stimuli for physiological processes such as development and wound healing but can also be deregulated in numerous conditions associated with accelerated ageing and reduced lifespan. Central to these stimuli are the transcription factor families Hypoxia Inducible Factor (HIF) and NF-kappaB. This project addresses fundamental mechanisms that regulate HIF and NF-kappaB in both normal and pathological responses and builds upon data linking these important transcription factors to a relatively unstudied protein called SINHCAF. SINHCAF, is associated with stem cells function but in differentiated cells controls cell cycle, proliferation and migration. The student on this project will investigate the nature, function and physiological significance of the interaction between SINHCAF, HIF and NF-kappaB pathways. The student will use state-of-the-art molecular cell biology techniques, Next generation sequencing approaches, with bioinformatic training, proteomics and CRISPR/Cas9 genome engineering.

This studentship offers an exciting opportunity to train in the laboratories of leaders in the field of HIF and NF-kappaB signalling using cutting edge technology to investigate a biological problem with direct relevance to disease.

HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]



Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Hypoxia induces rapid changes to histone methylation and reprograms chromatin. 2019. Science. 363, 1222-1226.

SINHCAF/FAM60A and SIN3A specifically repress HIF 2alpha expression. 2018. Biochem. J. 475, 2073-2090.

VHL inhibitor VH298 is a potent and selective chemical probe of hypoxic signalling downstream of HIFalpha hydroxylation. 2016. Nature Comms. 7, 13312.

HIF-1alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals. 2015. Dis. Models and Mech. 8, 169-181.

A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-kappaB-dependent liver regeneration and cancer.2016 Oncogene. 35(35), 4623-4632.

The NF-kappaB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. 2016. Oncogene. 35(26), 3476-3484.

Regulation of p53 and Rb Links the Alternative NF-kappaB Pathway to EZH2 Expression and Cell Senescence. 2014. PLoS Genet. 10(9):e1004642.

Strong anion exchange-mediated phosphoproteomics reveals extensive human non-canonical phosphorylation. 2019. EMBO J. 38(21):e100847.

DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κappaB p50 Transcription Factor. 2019. J Am Soc Mass Spectrom 30, 128-138

Dynamic phosphorylation of RelA on Ser42 and Ser45 in response to TNFα stimulation regulates DNA binding and transcription. (2016). Open Biology DOI: 10.1098/rsob.160055




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