A collaborative project funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 305564, research area FP7-HEALTH-2012-INNOVATION-1, topic HEALTH.2012.2.1.2-2: Systems medicine: Applying systems biology approaches for understanding multifactorial human diseases and their comorbidities.
By applying a systems-biological approach, the project SysmedIBD aims at revealing oscillating biological processes associated with the inflammatory bowel disease (IBD). IBD is a major health problem with severe co-morbidities, requiring life-long treatment. Oscillating processes such as circadian rhythms are well studied and modeled in a number of systems. In the case of IBD as in other inflammatory processes, one particular transcription factor (NF-kappaB) is known to play a key role. Recently, NF-kappaB-associated processes have also been shown to be oscillating. In this project, we will study NF-kappaB oscillation in chronic inflammatory bowel diseases in animal models and patient cohorts with immunosuppressive treatments and controls. The aim is to build an experimentally validated mathematical model of the NF-kappaB oscillation in the gut tissue.
The validated model will enable searching for critical molecular components of the NF-kappaB oscillation and to assess their relevance for the disease in patients.
Gaining control of the oscillation of biological pathways may provide new possibilities to influence biological processes like inflammation. Hence, we will search (assisted by the models and databases developed) for small molecules interfering with the NF-kappaB oscillation and validate selected candidates in experimental systems. Owing to its highly focused system biological approach, the project will generate substantial insights into key mechanisms underlying IBD.
GeneXplain will be involved in the dynamic simulation of the oscillating processed described above, and in the identification of suitable targets and drug candidates, which will then be experimentally validated by the partners.