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Evolutionary conservation of the diverse protein phosphorylation landscape

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  • Full or part time
    Prof C Eyers
    Prof E Veal
    Prof A Jones
  • 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

Protein phosphorylation is a key mechanism of regulating protein function that is conserved across the kingdoms of life. This reversible process allows cells to respond rapidly to environmental factors, be that e.g. growth factors, stressors, or contact adhesion with other cells. Phosphorylation modulates the functional properties of a protein, ultimately facilitating an intracellular response tailored to the specific extracellular stimuli. This process of phosphorylation-mediated signal transduction is tightly controlled, and dysregulation is strongly associated with disease aetiology. Recent development in the labs of the supervisors has revealed that many more amino acids are phosphorylated on human proteins that was previously appreciated. Consequently, the importance of these new types of phosphorylation events, and the roles that they play in cell signalling in mediating the response of cells to extracellular factors, need to be explored. We now wish to investigate conservation of these atypical types of phosphorylation across different species so that we can start to understand their importance in regulating key biological processes. This project will exploit state-of-the-art mass spectrometry-based proteomics to catalogue the phosphorylation landscape of a variety of model organisms. Using model systems where we can easily perturb expression of individual proteins, we will start to define putative roles for these novel modification events. In combination with computational analysis of protein sequence and modulated pathways, we will start to unravel the functions of these atypical types of phosphorylation, leading to enhanced understanding of their (patho)physiological roles.

The supervisor team comprises:
• Claire Eyers (Director, Centre for Proteome Research, https://www.liverpool.ac.uk/cpr/; Twitter: @ClaireEEyers) – https://www.liverpool.ac.uk/integrative-biology/staff/claire-eyers/
• Elizabeth Veal - https://www.ncl.ac.uk/medicalsciences/research/groups/profile/elizabethveal.html#background
• Andy Jones (Director, Computational Biology Facility, https://www.liverpool.ac.uk/computational-biology-facility/; Twitter: @andy___jones) – https://www.liverpool.ac.uk/integrative-biology/staff/andrew-jones/

You will join an established collaboration between the groups of Eyers and Jones, and benefit from a new collaboration with Dr. Veal in Newcastle, an expert in stress signalling and model organism manipulation. You will receive broad training in phosphorylation-mediated signalling; specific training will be provided in culture and manipulation of C. elegans, as well bacterial, fungal and human cells. You will also be trained in cutting edge proteomics techniques and the associated computational analysis tools for protein/proteomics data and pathway interrogation, making you highly employable across the field of biological sciences.

Expected outcomes include enhanced understanding of the roles and regulation of novel ‘non-canonical’ phosphorylation and the thus their roles in health and disease. These finding will likely lead to several high impact publications and conference presentations.

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

(2019) Strong anion exchange‐mediated phosphoproteomics reveals extensive human non‐canonical phosphorylation. EMBO J 38:e100847 doi.org/10.15252/embj.2018100847

(2017) Evaluation of parameters for confident phosphorylation site localization using an orbitrap fusion tribrid mass spectrometer. J Proteome Research 16:9 3448-3459

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

(2016) Direct and absolute quantification of over 1800 yeast proteins via selected reaction monitoring. Molecular & Cellular Proteomics 15:4 1309-1322

(2014) Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing. Nature Chemistry 6:65-74

(2018) NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting. Aging Cell. Jun;17:e12743

(2016) Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2 with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed Free Radicals Biol. Med. (2016) 95:333-48

(2015) A peroxiredoxin, PRDX-2, is required for insulin secretion and insulin/IIS-dependent regulation of stress resistance and longevity Aging Cell 14:558-68

(2018) Comparative qualitative phosphoproteomics analysis identifies shared phosphorylation motifs and associated biological processes in evolutionary divergent plants. J Proteomics 181, 152-159

(2015) The mzqLibrary - an open source Java library supporting the HUPO-PSI quantitative proteomics standard. Proteomics, 15, 2592-2596



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