High throughput MS-based histone PTM screening: Filling a void in pharmacoepigenetics.

01 November 2019 → 23 December 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Protein diagnostics
    • Clinical toxicology
    • Toxicology and toxinology not elsewhere classified
Project description

Epigenetics have taken centre stage in the study of diseases such as cancer, diabetes, and neurodegeneration. A new field is emerging that targets epigenetic modifications for therapeutic intervention: pharmacoepigenetics. Particularly in oncology, inhibitors of epigenetic-modifying proteins, i.e. epidrugs, have been successfully used in treatment. For nearly thirty years, it has been known that cancer cells exhibit abnormal DNA methylation patterns. However, the large scale analysis of histone posttranslational modifications (hPTMs), has lagged behind because classically, histone modification analysis has relied on site specific antibody-based techniques. Mass spectrometry (MS) is a technique that holds the promise to picture the histone code comprehensively in a single experiment. We have recently adapted the data-independent acquisition (DIA) strategy, i.e. SWATH, for the specific and accurate study of the histone fingerprint (hSWATH). In this project Sigrid Verhelst will make the transition from hSWATH as a fundamental research tool to a novel toxicoepigenetic assay. The candidate will focus on (i) increasing sample throughput during data acquisition and (ii) during data analysis, (iii) building a compound library on different cell types and (iv) adapting the assay to GLP. This novel toxicoepigenetic assay and the data it generates holds great potential for application in pharmaceutical industry, food science, clinical diagnostics,...