MDC Systems Biology Network

 
MDC Systems Biology Network (MSBN)

Cardiovascular and neurodegenerative disorders are among the leading causes of disability and death in Western societies (Lansbury, Nat Rev Neurosci 2004; Jessup, N Eng J Med 2003). At the same time there is still a striking lack of preventive measures and efficient therapies. Systems biology approaches are expected to increase our knowledge of the pathogenesis of these disorders considerably and to enable the development of effective drug treatments.
 
Both disease types are progressive, complex conditions that involve inherited as well asenvironmental factors. They are characterized by a relatively long asymptomatic phase and a shorter symptomatic stage which leads to acute heart failure and neuronal decay, respectively. There are certain shared molecular patterns: (1) Cardiac failure affects populations of adult cardiomyocytes, while neurodegeneration affects postmitotic neuronal cells, that similarly do not divide any more. (2) In both disorder types similar signaling cascades are changed, e.g. the NF-kB, JNK, or Akt pathways (Yuan, Nature 2000; Harjes, Trends Biochem Sci 2003; Garratt, Trends Cardiovasc Med 2003; Heinke Nat Rev Mol Cell Biol 2006). (3) In both illnesses, there are compensatory mechanisms which are able to protect the affected organ from the genetic or external perturbations for a very long time before it succumbs to the detrimental effects.
 
From all this, one can deduce that the underlying cellular processes bear significantsimilarities involving overlapping biological components even if the tissues affected aredifferent. We would like to promote the idea that it is advantageous to study both types of disease using a similar approach and that the systems biology analysis of cardiac disease will also stimulate the use of similar approaches in neurodegeneration and vice versa.
 
The major aims of MSBN are:

• Generation of mathematical models describing central cellular processes related to Alzheimer’s disease and cardiac hypertrophy.
• Theory driven experimental testing of hypotheses about disease mechanisms using well defined cell-culture and animal model systems.
• Generation of time-resolved and, where applicable, quantitative expression, microRNA,and protein interaction data for the cardiovascular and neurological disease processes using various functional genomics approaches and cell-based as well as in vivodisease model systems.
• Integration of experimental data, database establishment and construction ofprobabilistic models for the prediction of the key components and signaling pathways in the disease processes using bioinformatic tools, statistical approaches and simulation.
• Combination of theory driven approaches with data driven approaches to integrateinsights about pathomechanisms with results from comprehensive large scale analysis in formal theoretical descriptions of the disease processes.

 
The MSBN participates to the Helmholtz Alliance on Systems Biology:

The Helmholtz Alliance on Systems Biology is a joint initiative of several Helmholtz-centres and external partners and focuses on the elucidation of diverse complex disease mechanisms using a highly connected and interdisciplinary approach. The aim of the alliance is to use systemic approaches to promote the understanding of the causes of complex diseases and to develop new strategies for treating them.