Although most cancer cells actively proliferate, a rare subset of cells with stem-like properties and increased tumourigenic potential can remain quiescent for extended time. Since most cancer treatments only target dividing cells, quiescence represents a major therapeutic challenge. Indeed, in many tumour types quiescent cells are the key substrate of relapse and further disease evolution. The mechanisms controlling quiescence remain largely unknown, and transcriptomic analysis of quiescent cells has yielded only limited insights. This might be at least partly due to i) quiescent cells having globally reduced transcriptional activity, ii) poor overall concordance between transcript and protein expression, and (iii) the importance of post-translational modifications in signal transduction, particularly in processes such as the cell cycle.
The successful candidate will investigate the proteome of quiescent cancer cells, focusing on leukaemia and glioblastoma, to provide new insights into quiescence regulation and guide the development of new therapeutic strategies aimed at their eradication. They will employ and further develop: (i) techniques for isolating cancer cell subsets, (ii) sample preparation methodologies for ultra-low protein input, (iii) sensitive discovery and targeted mass-spectrometry techniques, and (iv) computational data analysis workflows. Proteomic findings will be integrated with available genomic, transcriptomic, epigenetic, and metabolic descriptions of quiescence.