Exploring the roles of dynamic atypical protein phosphorylation in cancer


Proteins are extensively regulated by dynamic, often reversible post-translational modifications (PTMs). This process allows cells to respond rapidly to environmental factors, be that e.g. growth factors, stressors, or contact adhesion with other cells, ultimately allowing cells to adapt. Importantly, protein modifications have been shown to be differentially regulated in numerous diseases, including cancer, serving as both markers of disease and facilitating treatment stratification.

Protein phosphorylation is a key PTM that is known to be differentially affected during cancer, and inhibitors of enzymes that regulate phosphorylation are often used as clinical therapeutics. However, studies to date focus on phosphorylation of serine, threonine, and tyrosine residues. Having recently demonstrated that non-canonical phosphorylation of 6 other amino acids is extensive in human cells, we have an interest exploring the dynamics and regulation of these novel phosphorylation events in cell signalling and as drivers/markers for cancer.

Specific objectives

  1. Apply novel quantitative mass spectrometry-based analytical pipelines to explore and quantify atypical phosphorylation in U2OS osteosarcoma cells exposed to cellular stimuli/stressors/inhibitors, including regulators of protein kinase networks and mitochondrial dysfunction.
  2. Exploit a variety of computational strategies e.g. residue conservation, motif discovery, pathway analysis, mining protein-protein interaction database, to cross-correlate PTM types and sites and predict interplay and regulatory mechanisms.
  3. Undertake cell and tissue-based studies to understand the mechanisms of regulation of key modified targets and potential use as clinical markers.


  1. Understanding of the extent of phosphorylation on human proteins, and their contextual information, with a focus on atypical phosphorylation
  2. Experience in presentation of findings at appropriate analytical/technology and cell signalling meetings
  3. Training in fundamental MS and computational biology, making future employability high
  4. Collaboration with clinical academics


The project is suited to a student with at least a good B.Sc. Upper Second in e.g. Biochemistry, Chemistry or related disciplines.

Applications will be reviewed until a suitable candidate is appointed - the deadline may therefore be subject to change.



Open to students worldwide

Funding information

Self-funded project

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. 

Assistance will be given to those who are applying to international funding schemes. 

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. 

New self-funded applicants may be eligible for a tuition fees bursary.

Details of costs can be found on the University website: https://www.liverpool.ac.uk/study/postgraduate-research/fees-and-funding/fees-and-costs/



  • Hunter JE et al. Mutation of the RelA (p65) Thr505 phosphosite disrupts the DNA replication stress response leading to CHK1 inhibitor resistance. Biochemical Journal (2022) 479 (19)2087-2113 doi.org/10.1042/BCJ20220089
  • Daly LA et al. (2021) Oxygen-dependent changes in HIF binding partners and post-translational modifications regulate stability and transcriptional activity. (2021) Science signaling 14 (692), eabf6685 DOI: 10.1126/scisignal.abf6685
  • Hardman G et al. Strong anion exchange-mediated phosphoproteomics reveals extensive human non-canonical phosphorylation.  The EMBO J. (2019) e100847.  org/10.15252/embj.2018100847