Systems Biology ? Systems Biology ≈ Network Biology GOAL: develop a quantitative understanding of the biological function of genetic and biochemical networks gene A gene C gene E gene B gene D gene F INPUT OUTPUT - function of gene product A-F can be known in detail but this is not sufficient to reveal the biological function of the INPUT-OUTPUT relation - a system approach (looking beyond one gene/protein) is necessary to reveal the biological function of this whole network - what is the function of the individual interactions (feedbacks and feedforwards) in the context of the entire network ? Alternatively, Systems Engineering + Molecular Biology Systems Engineering Molecular Biology Systems Biology = Applying Systems Engineering concepts to Biological Systems OR2 OR3 λλ λλ λ λ OR2 OR3 λλ OR2 OR3 λλ λλ K 1 K 2 A traditional molecular biologist would ask: - what is the molecular structure of the cI dimer ? - what is DNA sequence recognized by the cI dimer ? - what are the essential amino acids in cI responsible for dimerization ? - what are the values for K 1 and K 2 ? - is the sequence conversed during evolution ? Focussed on the molecule cI. molecular biology vs systems biology OR2 OR3 λλ λλ λ λ OR2 OR3 λλ OR2 OR3 λλ λλ K 1 K 2 A systems biologist would ask: - what is the functional role of the feedback ? - how can this lead to a hysteretic switch ? - what is the role of noise in determining the stability of the switch ? - is the performance of the switch sensitive to small changes in the parameters (fine-tuned) of not (robust). - how are these parameters changed when this module is cross-talking to other modules. Focussed on the network architecture. molecular biology vs systems biology Goal of this course: - provide you with the essential mathematical tools to be able to model network modules, such as biological switches, oscillators, filters, amplifiers, etc. - provide you with lots of example of biological problems that can be successfully tackled with a systems biology approach (first well-stirred systems, second diffusion- dominated systems) by discussing recent recent papers.