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A4: Introduction to Systems Biology

The module introduces mathematical approaches and systems biology concepts of cellular processes, as they are important for therapeutically relevant systems. The overall aim of the module is to learn and understand how prior knowledge on the targeted system (e.g., based on in vitro data or systems biology models of endogenous compounds) can be exploited for and integrated into the analysis of preclinical and clinical data.


The module includes important deterministic and stochastic approaches to biochemical reaction kinetics, model reduction techniques (e.g., the quasi-steady state approach/singular perturbation analysis), network motifs and the integration of cell-level models and pharmacokinetic models. This allows us to establish the link to empirical models as introduced in the A1 PK/PD module (Emax, non-linear CL etc) and important physiological processes as part of PBPK models (establishing the link to the A2 PBPK module). Techniques are exemplified for the EGFR signalling system and the drug-host-virus system in HIV disease.

Illustrative schedule

TimeMondayTuesdayWednesdayThursdayFriday
8:45 – 10:45Introduction to Systems BiologyHands-on: Matlab recap on solving ODEs; ligand-receptor binding (theory)Mathematical modelling tools II: Model reduction techniques (QSSA)Introduction to disease modelling: HIV infection modelsNetwork motifs and modules
30 minCoffee break
11:15 - 13:00Mathematical modelling tools I: Deterministic reaction kineticsMathematical modelling tools I: Deterministic reaction kinetics (con't)Hands-on: cell-level PK/PD modellingHands-on: deterministic HIV infection models (incl. mutants)Hands-on: targeting a signalling cascade
60 minLunch break
14:00 - 16:00Guest discussion on ethical aspect in pharmacometricsHands-on: ligand- receptor binding (implementation)Hands-on: cell-level PK/PD modelling (con't)Mathematical modelling tools III: Stochastic reaction kinetics + hybrid modelsHands-on: targeting a signalling cascade (con't); Summary & closing; end
15 minCoffee break
16:15 - 17:45Guest talk & discussion (con't), end: 17:00.Integration of systems biology models into PK/PD modelsUnderstanding and reducing complex systems pharmacology modelsHands-on: deterministic HIV infection models (incl. drugs); stochastic HIV infection models
EveningSocial Event (jointly with A3 Systems Biology module)

Contributions:

  • Prof. Wilhelm Huisinga; theoretical lectures
  • PharMetrX PhD students (2nd/3rd year); hands-on exercises
  • External contributions by our faculty members
Venue: Universität Potsdam/Germany
 
Frequency: Every year, typically in September.
 

Hard- and software

  • Please bring your own laptop.
  • MATLAB® (The MathWorks), please bring your own Matlab version if possible. Note that there exists a student version (incl. many toolboxes) for appr. 90 USD for PhD students.

Literature