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Molecular and cellular mechanisms of inflammation and cell death

Research project P5/12 (Research action P5)

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Description :

In this research proposal we will investigate in a multi-disciplinary approach the different mechanisms which lead to the phenomenon of 'inflammation' with its various side-effects, both at the cellular and multi-cellular level; further, we will also try to get a better insight into inflammatory affections in an organism and how the organism reacts on inflammation; finally, we will analyse the possible tools to specifically interfere with inflammatory diseases.

This research proposal is presented as 5 distinct 'work packages', which, each of them, contains a well- defined part of the various research goals stipulated. In work packages 1 and 2, we intend to investigate the molecular mechanisms in the nucleus and cytoplasm of the cell, which lead to the activation and transactivation of the central and crucial, stress-mediated and inflammation-related transcription factor NF-chi B; it also includes some research tasks to resolve and understand the consequences of cellular situations, in which the normal activation pathways of NF-chi B are disturbed or blocked.

Cell death is a phenomenon, which is closely linked to inflammation and in which the transcription factor NF-chi B plays a determinative role. Therefore, work package 3 is entirely intended to study the mechanisms controlling cell death; moreover, various approaches will also be undertaken to analyse different systems and examples, in which cell death control and intracellular communication are disturbed.

In work package 4, the unicellular level is no longer considered, but full attention will be given to the living conditions of different cell types in 'community' (as it actually is the case in a real natural tissue), as well as to the intercellular communication pathways and mutual interference of living cells by co-culture.

Finally, work package 5 is completely devoted to analyse the mechanisms of inflammation at the level of a living organism. By means of various inflammatory model systems in mice, we will analyse the anti- and/or pro-inflammatory potential of different cytokines. We will also concentrate on the molecular mediators and transcription factors of these cytokines (see work packages above), thus fully underscoring the global and interrelated character of this entire research proposal.

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