Mathematical modeling of complex biological phenomena and diseases is an important approach to combine the accumulating amount of data in biological investigations and the increasing qualitative understanding of cellular operation in a productive way. The realization of genomic information in a biological instance is ensured by a complex network of processes. The dynamic behavior of such processes cant be understood intuitively. Only a comprehensive approach allows the understanding of complex system behavior like optimal regulation or adaptation. We use mathematical models to describe and investigate cellular processes and regulatory links from gene expression to metabolism.
Mathematical modeling of stress response and signal transduction in yeast
EU - Project
How can cells respond to changes in the environment? All eukaryotic
cells use mitogen-activated protein kinase (MAPK) cascades as central cores
of complex signal transduction pathways that respond to a variety of external
stimuli and regulate numerous cellular responses. The investigation of
these pathways leads to a couple of questions: What ensures the fidelity
of the signaling - especially in cases when the same protein kinase is
involved in more than one pathway? How is the signal processed in the pathway?
What prevents overstimulation (switch off)?
In cooperation with a Swedish group (Stefan
Hohmann, Göteborg University) we model such processes, identifying
individually steps, describe the dynamics with a system of ordinary differential
equations.
People: Jörg Schaber, Edda Klipp
Mathematical modeling of aging processes in yeast
EU - Project EST Systems Biology
Yeast cells have a genetically defined replicative life span. Aging
is a complex process that is influenced by a series of external and internal
factors. In this project different possible cause of aging will be examined
theoretically and experimentally. The first step for this is the development
of a computational model, which examines the plausibility of the different
scenarios. In particular the influence of the size difference between mother
and daughter for the division process will be analysed, since it is to
be assumed that this parameter is of important influence for the number
of possible divisions. The relation of the aging processes to the regulation
of cell cycle processes will be investigated using integrated mathematical
models. Experimentally, the size distribution can be measured with a high
throughput flow cytometer. Then, cells are analysed with respect to their
replicative potential in relation to size. The combination of molecular
biology, global expression measurements, and bioimaging on the one hand
and dynamic modelling on the other hand will allow to rationalise observed
phenomena and describe the process.
This project is performded in cooperation with Thomas
Nyström and Stefan
Hohmann (Göteborg University).
People: Edda Klipp, Axel Kowald
Modeling of the development of complex diseases
The human chromosome 21 is sequenced, an increasing number of its genes
are annotated. Nevertheless, the molecular reasons and the causal track
of Down syndrome, a human disorder caused by a third copy of the chromosome
21, remain open questions.
The gene for the most important antioxidant enzyme, superoxid dismutase
(SOD), lies in humans on chromosome 21 and its activity is increased in
patients with Down syndrome. It catalyses the dismutation of superoxide
radicals to hydrogen peroxide. But, counter intuitively, increased lipid
peroxidation and an increased oxidative stress are associated with the
increased SOD expression. With a modeling approach we investigate, how
the oxidative stress arises and how it changes the cellular balance. Furthermore,
the relation between damage of mitochondria and aging is investigated.
We tested different scenarios published in literature and identified an
additional mechanism which agrees well with experimental observations.
People: Axel Kowald, Edda Klipp
Development of a Modeling and Simulation Environment
EU-Project EMI-CD
A computational environment for whole-cell-modeling is under development in co-operation with the Bioinformatics group (Ralf Herwig, Christoph Wierling) at the MPI for Molecular Genetics.
People: Wolfram Liebermeister, Axel Kowald, Edda Klipp
Systems Biology and Text mining
Understanding and modeling of biological systems relies on the availability of experimental results measuring chemical and physical properties and dynamic changes of the system. The use of appropriate kinetic parameters is crucial for successful performance of numerical simulations. Since there is no collection of preprocessed data for this purpose, but a huge amount of these data has been published in scientific journals, a comprehensive literature search is necessary. Together with the group of Ulf Leser, Humboldt University, we develop an automated procedure for retrieval and classification of biochemical texts to detect relevant data.
People: Sebastian Schmeier, Axel Kowald, Edda Klipp
Kinetikon
To make accumulated knowledge about the kinetics of individual reactions available in a concise form, we develop a database devoted to storing of rate expressions and respective experimental data. This will be publicly open as soon as possible.
People: Stephan Menz, Christof Dehmel, Axel Kowald, Edda Klipp
SBMLMerge
We are currently developing a methodology for merging biochemical models in the common SBML format. Our algorithm is implemented in the command line tool SBMLMerge.
People: Wolfram Liebermeister, Marvin Schulz, Jannis Uhlendorf