DC9
Develop mathematical models linking SAM and Acetyl-CoA to protein acetylation and methylation
Background: Turnover of site-specific PTMs is assessed by introducing stable isotopes into the modifying groups. Generally, these are derived from extracellular precursors (such as 13C-glucose, acetate or methionine). The intracellular conversions into the modifying agents (acyl-CoA, SAM etc.) and the corresponding time courses are complex and vary dependent on the experimental conditions. To accurately determine the PTM dynamics requires the development and implementation of complex correction algorithms that account for time courses of label incorporation, incomplete saturation, label dilution etc. Objectives: (1) Develop a modelling-based approach to correct stable isotope-based protein modification for cofactor biosynthesis dynamics (2) Build and extend both small scale dynamic and genome scale metabolic models to reflect substrate requirements through protein modifications and consequently potential limitations for PTMs.