Post-translational modifications (PTMs) are essential adaptations to proteins, which allow cellular systems to adapt rapidly to their environment, through signalling cascades. The most studied PTMs include phosphorylation, acetylation, methylation, ubiquitination and SUMOylation, amongst 100s of others. Their roles in normal cellular regulation include activation and repression of other proteins, signalling for protein degradation, changing protein-protein interaction networks and many others.
PTMs have been implicated in almost all types of biological processes and as a consequence, also in multiple diseases, including cancers, neurodegeneration, infectious and autoimmune diseases. As an example, it is very common for sites of PTMs, particularly phosphorylation and ubiquitination, to be mutated in cancer, leading to loss of normal cellular checkpoints.
In this project, you will be joining an international consortium, called PTMExchange, led by Prof Andy Jones at the University of Liverpool, collaborating with partners at the European Bioinformatics Institute (EBI, working on the PRIDE and UniProt databases) and the Institute of Systems Biology (Seattle; PeptideAtlas). We are performing very large scale computational re-analyses of publicly available mass spectrometry (MS) data, to learn what PTM sites can be confirmed on proteins [1]. We are then performing downstream analyses to understand how sites of modification have evolved [2], the enzymes responsible, and make predictions about how different PTMs work together, via a mechanism called crosstalk.
In this project, we will particularly focus on lysine modifications in humans – particularly acetylation, methylation, ubiquitination and SUMOylation. We will integrate data on PTM sites with known genetic variants, to explain potential disease mechanisms, and form hypotheses for laboratory experiments. We have a supportive network, working closely with staff and PhD students in Prof Jones’ group, and with the Computational Biology Facility (CBF) at Liverpool, where you will receive training (as needed) in coding, data science and machine learning, via training courses and 1:1 mentoring.
The project will include a placement in the lab of Prof Matthias Trost (Newcastle University), a leading expert in proteomics, particular focussed on ubiquitination, to learn more about MS and data generation.
[1] Ramsbottom, K.A. et al. Method for Independent Estimation of the False Localization Rate for Phosphoproteomics. Journal of Proteome Research 21, 1603-1615 (2022)
[2] Kalyuzhnyy, A. et al. Profiling the Human Phosphoproteome to Estimate the True Extent of Protein Phosphorylation. Journal of Proteome Research 21, 1510–1524 (2022).
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);
· a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, 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;
· copies of your relevant undergraduate degree transcripts and certificates;
· a copy of your IELTS or TOEFL English language certificate (where required);
· a copy of your passport (photo page).
A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.
In addition to the above items, please email a completed copy of the Additional Details Form (as a 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]
The deadline for all applications is 12noon on Monday 9th January 2023.
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