DC8
Dynamic interplay and crosstalk between hub molecules (acetyl-CoA, SAM) and their PTMs (histone acetylation & methylation)
Background: Protein modifications play a central role in the regulation of cellular homeostasis. However, very little is known about the relationships between cellular hub molecule pools and the resulting protein modifications. In this project, we will investigate the subcellular dynamics of hub metabolites (acyl-CoAs, SAM, ATP) and how these molecules control protein modification signatures (acylation, methylation, phosphorylation) and regulatory circuits.
Objectives: 1) Establish mass spectrometry-based approaches to quantify acyl-CoA and SAM production and their biosynthetic intermediates. 2) Stable-isotope-based quantification protein modification (acylation, methylation) dynamics by high resolution LC-MS. 3) Investigation of subcellular turnover of hub molecules (acyl-CoAs, SAM, ATP) and protein modification dynamics and their interdependencies, including protein modification crosstalk.