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PEROXISOMES: Integrated Project to decipher the biological function of peroxisomes in health and disease
- Abstract
- Although peroxisomes are essential for life, the various functions and dynamics of this organelle in health and disease are only poorly understood. Most inherited peroxisomal disorders in humans have a low incidence but collectively they represent an enormous burden on affected individuals, families and society. A detailed understanding of biogenesis and function of this organelle is required for developing therapeutic strategies. To bridge the gap between the scarce knowledge about peroxisomes and their importance for living organisms, we will establish genomic, proteomic and metabolomic platforms focussed on peroxisomes. We will identify novel peroxisomal matrix and membrane proteins and gather comprehensive knowledge about their functions. Using this information, we should be able to decipher the molecular mechanism of so far uncharacterised peroxisomal disorders and open up novel diagnostic and therapeutic opportunities. Genome-wide gene expression and biochemical analyses of 14 different mouse models of peroxisomal deficiencies will reveal why differing phenotypes occur even when the same metabolic pathway is disturbed. Mouse genetics will be used to evaluate the role of peroxisomes in different cell types during development and in adulthood. Because evidence is emerging for a role of peroxisomes as modulators in diseases of complex inheritance, such as arteriosclerosis, cancer and Alzheimer's disease, we will screen appropriate databases to detect dysregulation of genes encoding peroxisomal proteins. Tissue microarray analysis, cDNA chip and quantitative RT-PCR analysis will be used to verify the results with the final goal to develop diagnostic tools. The role of peroxisomes in Alzheimer's disease and in chronic metabolic liver diseases will be analysed and the biogenesis and dynamics of this organelle deciphered. Only with this integrated EU project will we be able to elucidate the role of peroxisomes in living organisms in the near future.
- Local Subprojectlead:
- Höfler Gerald
- Duration:
- 01.01.2005-31.12.2008
- Programme:
- EU (FP-6)
- Subprogramme
- Life sciences, genomics and biotechnology for health
- Type of Research
- basic research
- MUG Research Units
- Center for Medical Research (ZMF)
- Diagnostic and Research Institute of Pathology
- Project partners
- Abteilung für Neurologie, Medizinische Universität Wien, Austria
- Academic Medical Center, University of Amsterdam, Netherlands
- Biochemie-Zentrum Heidelberg, Universität Heidelberg, Germany
- Dept. of Basic and Applied Biology, University of L'Aquilla, Italy
- Dept. of Biochemistry and Molecular Biology, University of Vienna, Austria
- Institutio de Biologia Molecular e Cellular, Universidade de Porto, Portugal
- Karolinska Institut, Sweden
- Katholieke Universiteit Leuven, Belgium
- Max-Planck-Society, Germany
- Oridis Biomed, Forschungs- und Entwicklungs-GmbH, Austria
- Ruhr-Universität Bochum, Germany
- Université de Bourgogne, France
- Universiteit Gent, Belgium
- University of Oulu, Finland