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.
|8:45 – 10:45||Introduction to Systems Biology||Hands-on: Matlab recap on solving ODEs; ligand-receptor binding (theory)||Mathematical modelling tools II: Model reduction techniques (QSSA)||Introduction to disease modelling: HIV infection models||Network motifs and modules|
|30 min||Coffee break|
|11:15 - 13:00||Mathematical modelling tools I: Deterministic reaction kinetics||Mathematical modelling tools I: Deterministic reaction kinetics (con't)||Hands-on: cell-level PK/PD modelling||Hands-on: deterministic HIV infection models (incl. mutants)||Hands-on: targeting a signalling cascade|
|60 min||Lunch break|
|14:00 - 16:00||Guest discussion on ethical aspect in pharmacometrics||Hands-on: ligand- receptor binding (implementation)||Hands-on: cell-level PK/PD modelling (con't)||Mathematical modelling tools III: Stochastic reaction kinetics + hybrid models||Hands-on: targeting a signalling cascade (con't); Summary & closing; end|
|15 min||Coffee break|
|16:15 - 17:45||Guest talk & discussion (con't), end: 17:00.||Integration of systems biology models into PK/PD models||Understanding and reducing complex systems pharmacology models||Hands-on: deterministic HIV infection models (incl. drugs); stochastic HIV infection models|
|Evening||Social Event (jointly with A3 Systems Biology module)|
- Prof. Wilhelm Huisinga; theoretical lectures
- PharMetrX PhD students (2nd/3rd year); hands-on exercises
- External contributions by our faculty members
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.
- W. Huisinga, Handouts of slides.
- Edda Klipp et al.,''Systems Biology - A Textbook'', Wiley-Blackwell, 2009.
- Uri Alon, ''An Introduction to Systems Biology: Design Principles of Biological Circuits'', Chapman & Hall, 2006.
- Further references will be provided during the course.