SP 4

Cell physiology modelling and proteomics

Proteomic analysis of patient samples determines the concentration of thousands of proreins individually for each patient. We thus relate cellular parameters to the individual disease profile. Mathematical modelling relates protein concentrations to function by simulating contraction with the individual parameter sets. As the case may be, it indicates gaps in the quantification of patient samples and/or in our understanding of disease mechanisms.

Mathematical simulations of intracellular concentrations. Three dimensional visualisation of a snap shot of spatially resolved Calcium concentration dynamics at 200.0 ms after activation. A - Isoconcentration surfaces show cytosolic Calcium in green for 1.1 µM and red for 2.0 µM . B - The yellow isosurface shows free sarcoplasmic Calcium for 550 µM . There are 320 Calcium release units per z-disc, with an average of 50 RyR channels and 12.5 LC channels per unit.

The work schedule comprises:

  • development of a detailed mathematical model of excitation contraction coupling
  • proteomic analysis of patient smaples
  • simulation of patientspecific cell function
  • comparison/verification with patient specific function data from imaging
Comparative analysis of different interactomes. Proteins interacting specifically with one component are visualized using a vulcano-plot. Significant binders are shown in blue, background binders in red.