We are an interdisciplinary research group combining techniques in synthetic organic chemistry, biochemistry, cell culture and mass spectrometry to investigate the molecular mechanisms of diseases. Our aim is to provide novel understanding of disease pathologies, investigate new therapeutic targets and identify new biomarkers for diagnostics.
Proteins with defined post-translational modifications as tools to explore biology
We create synthetic proteins carrying defined post-translational modifications (PTMs) using a novel chemistry, posttranslational chemical mutagenesis. Initially developed in the lab of Ben Davis at the University of Oxford, this synthetic chemistry technology enables to make proteins with chemically-defined mimics of post-translational modifications that differ in a single atom or atom group from their naturally-occurring counterparts. This enable us to study biological processes dependent on posttranslational modifications (including methylation, phosphorylation, glycosylation etc.) with a great level of detail.
We particularly focus on the role of histone post-translational modifications in the etiology of multiple myeloma and how we can identify novel epigenetic drug targets for patients with relapsed or refractory multiple myeloma (see our research on myeloma).
Small molecule inhibitors of pathological epigenetic signalling
Our ability to generate synthetic proteins with defined PTMs also allows us to design small molecule inhibitors interfering specifically with the recognition of a given PTM. For this, we generate close-to-nature analogues and substrates for drug targets (enzymes) acting on the post-translational modification of interest and develop an assay to measure the activity of our inhibitors.
- Nadal S, et al. “Synthetic post-translational modification of histones.” Curr. Opin. Chem. Biol. 2018, 45, 35-47.