Overview
On this self-funded project, we aim to explore the dynamics and regulation of novel phosphorylation events in cell signalling and as drivers/markers for cancer.
About this opportunity
Proteins are extensively regulated by dynamic, often reversible post-translational modifications (PTMs). This process allows cells to respond rapidly to environmental factors, be that, eg 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
- 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
- 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
- Undertake cell and tissue-based studies to understand the mechanisms of regulation of key modified targets and potential use as clinical markers.
Outcomes
- Understanding of the extent of phosphorylation on human proteins, and their contextual information, with a focus on atypical phosphorylation
- Experience in presentation of findings at appropriate analytical/technology and cell signalling meetings
- Training in fundamental MS and computational biology, making future employability high
- Collaboration with clinical academics.
Who is this opportunity for?
This project is open to self-funded UK and international applicants. The project is suited to a student with a minimum 2:1 BSc degree (or an international equivalent) in, for example, Biochemistry, Chemistry or related disciplines.