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Multi-omics investigations for enhanced understanding of NF-κB mediated drug resistance


Project Description

We have an established system that can be used to investigate the role of NF-κB signalling in the cancer cell response to DNA replication stress and have generated cell lines which are resistant to treatment with a highly selective and specific CHK1 inhibitor (CCT244747). These models will be analysed by a series of analytical platforms based on mass spectrometry which probe different function levels of the cell. These include assessing cellular metabolism using metabolomics, determining changes in (phospho)proteome using proteomics, and gene expression profiling using RNAseq. The quantitative perturbation to the system with different levels of CCT244747 is advantageous because cellular responses can be ‘correlated’ mathematically and this will be done using computational approaches and visualised on metabolic networks and signalling pathways.

The supervisory team:
• Roy Goodacre – https://www.liverpool.ac.uk/integrative-biology/staff/roy-goodacre/
• Neil Perkins – https://www.ncl.ac.uk/medical-sciences/people/profile/neilperkins.html
• Claire Eyers – https://www.liverpool.ac.uk/integrative-biology/staff/claire-eyers/
• Andy Jones – https://www.liverpool.ac.uk/integrative-biology/staff/andrew-jones/

The student will receive training in several different and complementary disciplines that are needed for systems biology understanding of cellular phenotypes, which will make their future employability high. The expected outputs include: an enhanced understanding of NF-κB mediated drug resistance in cancer cells, which will lead to several publications in good journals and conference presentations, in terms of this specific application but also the development of integrative omics analyses.

Whilst predominantly based in Liverpool, the student would spend time in Newcastle throughout the PhD programme, as the model systems that will be studies are based on pioneering work from NP’s laboratories on NF-κB and cell signalling. In Liverpool the student will join a dynamic research group based in IIB where the focus is to investigate cellular metabolism and to integrate this within metabolic and transcriptional regulation.

HOW TO APPLY
CV, Letter of Application, 2 References by email to
Informal enquiries may be made to

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.

The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £6,000 per year.

A fee bursary may be available for well qualified and motivated applicants.

Details of costs can be found on the University website:
View Website

References

Rattray, N.J.W., Trivedi, D.K., Xu, Y., Chandola, T., Eendebak, R.J.A.H., Johnson, C.H., Marshall, A.D., Mekli, K., Rattray, Z., Tampubolon, G., Vanhoutte, B., White, I.R., Wu, F.C.W., Pendleton, N., Nazroo, J. & Goodacre, R. (2019) Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms identified as drivers behind human frailty. Nature Communications 10: 5027.

Moles, A., Butterworth, J.A., Sanchez, A., Hunter, J.E., Leslie, J., Sellier, H., Tiniakos, D., Cockell, S.J., Mann, D.A., Oakley F. & Perkins, N.D. (2016) A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-κB-dependent liver regeneration and cancer. Oncogene 35, 4623-32.

Hardman, G., Perkins, S., Brownridge, P.J., Clarke, C.J., Byrne, D.P., Campbell, A.E., Kalyuzhnyy, A., Myall, A., Eyers, P.A., Jones A.R. & Eyers C.E. (2019) Strong anion exchange‐mediated phosphoproteomics reveals extensive human non‐canonical phosphorylation. EMBO J 38:e100847

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