Computational Systems Biotechnology 2

Lecturer: Prof. Dr. Wolfgang Wiechert, Dr.-Ing. Stephan Noack
Lecture: 2 hours
Tutorials: 1 hour
Lecture date: See RWTHOnline
Lecture notes: Will be shared on SCIEBO
Lecture semester: Sommersemester
Language: German
Type of exam: Oral

(Molecular) Systems Biology (SB) is a modern discipline in the life science. Seen from an engineering perspective, SB consequently applies process engineering methodology to the description of processes within a living cell. Thus, SB is concerned with structure and function of complex biochemical interaction networks. The most important foundation of SB is the modern arsenal of high-throughput analytical methods (“omics” methods) for the detailed analysis of genetic and metabolic processes in vivo. The hereby generated large and complex data sets are analyzed with the aid of mathematical models yielding an improved systems understanding. The models also enable qualitative predictions to be made which are needed, for example, for the optimization of production organisms or for the targeted design of new informative experiments. For this reason, SB has also an important foundation of modern synthetic biology.

The two independent lectures CSB 1&2 are intended (presently in German language) for an interdisciplinary audience (CSB 1 in SS, CSB 2 in WS). The focus is on computer supported aspects of systems biology since experimental and bioanalytical foundations are already presented in other lectures at RWTH. The level of abstraction is chosen in such a way that students from different academic courses (particularly engineers and biotechnologists) can follow. If necessary, specific teaching modules are introduced for supplying the required mathematical or biological contents. The lectures integrate presentation units with exercises and short projects supported by different software systems (MATLAB, Omix, Madonna, Maple etc.).

CSB 2 is concerned with modeling of dynamic and steady states of biochemical networks based on systems of differential equations. The description of every single reaction step is given by enzyme kinetic formalisms. Major aim is to understand how living cells chose and regulate their physiological state in dependency on their environment. CSB 2 is mathematically more demanding than CSB 1. For an understanding of the used methods knowledge in linear algebra (matrices, own values) and multi-dimensional differential calculus (partial derivatives, Jacobian) are necessary. Engineers do not need any deeper knowledge of biology because the lecture is example based. Several themes of the lecture are:

  1. Basic concepts
    • general network model
    • analysis of stability and sensitivity
    • simulation- and analysis tools
  2. Advanced enzyme kinetics
    • quasi steady state
    • enzyme kinetic
    • alternative kinetic formats
  3. Metabolic regulation
    • simple regulation architectures
    • metabolic control analysis
    • large metabolic networks
  4. Genetic regulation
    • genetic circuits
    • signal transduction
  5. Dealing with missing information
    • parameter estimation & prediction
    • experimental design
    • model simplification
  6. Stochastic modeling
    • SSA formalism
    • Gillespie algorithm
    • simple examples
  7. Reaction-Diffusion-Systems