Proteomics Exploration of Lysine Methylation in Health and Disease (ProMethHD)

Methylation of lysine residues (Kme) in proteins is a dynamic post-translational modification (PTM) which often serves a regulatory function and is frequently dysregulated in cancer.

Mass spectrometry (MS)-based proteomics is the method of choice for PTM analysis and affinity agents for specific PTMs are typically used to enrich modified peptides for analysis.

Today, there is no available method or workflow for large-scale analysis of Kme and, consequently, the PTM is underexplored.

This project will make use of truly novel Kme affinity agents to enrich modified peptides for MS and also establish large-scale targeted MS for Kme analysis.

Kme affinity agents are generated by i) selection from recombinant antibody libraries using the phage display technology and ii) by isolation of naturally evolved Kme binding protein domains.

The novel MS-based workflows will be used to globally explore the abundance and regulation of Kme alone, as well as its interplay with other PTMs, in human cells and tissues. Kme modulating enzymes are frequently mutated in cancer and are emerging drug targets. This project will also explore the clinical utility of Kme as a biomarker for ovarian cancer.

The proposed 4-year project will corroborate the establishment of a new PTM proteomics-oriented research group at the Department of Immunotechnology, Lund University.

The group will synergize with local leading expertise on affinity agents and integrate with on-going clinically oriented projects.