Projects
COST CM1001 Action: Chemistry of nonenzymatic protein modification ─ modulation of protein structure and function
Support: EU – European Cooperation in the Field of Scientific and Technical Research und Chemistry and Molecular Sciences and Technologies
The complexity of human life arises from some twenty thousand genes, and results due to alternative splicing mechanism in approx. 100000 proteins. By posttranslational modifications these proteins are converted into an array of some 1.5 million different functional entities. Interestingly, this conversion can either be enzymatically controlled and regulated, or may have an apparently random aspect due to non-enzymatic reactions. Proteins undergo a wide array of non-enzymatic post-translational modifications. Such modifications of proteins are often determined by their environments, their structural features and by a number of protecting structures, and also by free radicals generated in their vicinity. Non-enzymatic protein modifications are, therefore, not random, but occur in a non-regulated manner and depend largely on the protein and its environment.
Lipofuscin formation in senescent cells: role of lysosomal vitamin E
Support:Deutsche Forschungsgemeinschaft
Aging is always accompanied by the accumulation of intracellular protein aggregates. This is especially true for non-dividing, including post-mitotic, cells. These protein aggreagates, often referred to as lipofuscin, are able to influence the cellular metabolism. An age-related increase of lipofuscin-triggered senescence-related oxidation processes is postulated. Such an enhanced oxidation, partially located in the lysosomes, would lead to a damage of lysosomal membranes and perhaps to the rupture of lysosomes, leading to a further deterioration of cellular metabolism and perhaps to cell death via apoptotic pathways. In this project we approach this postulate and test what role the lysosomal vitamin E concentration plays in the stabilization of this membrane.
Novel strategies for the enhancement of the potency of nutraceuticals with low oral bioavailability and their application in novel functional foods for optimum protection of the aging brain
Support: BMBF
Curcumin is a nutraceutical currently intensively investigated for its potential use as a therapeutic or preventive agent against a number of degenerative diseases, including cancer and Alzheimer's disease. Curcumin is the coloring agent derived from the root of the plant Curcuma longa and gives the yellow color to the spice curry, in which it is found in significant amounts. It is also commonly used, under the designation "E 100", as a coloring agent by the food industry. Because of its potent health beneficial activities, such as antiinflammatory, antioxidant, and anticancer effects, to name only a few, researchers have attempted to enhance the uptake and retention of the phytochemical in the body. Curcumin, however, remains a very difficult compound to detect in the body, because it is taken up into the body to a limited extent and subsequently rapidly metabolized and excreted from the organism. Hence, an important question in this context remains largely unanswered: Could the health beneficial activities of Curcumin be enhanced if more of the active compound would reach the site of action, e.g. the brain?
MARK-AGE
Support: EU
European Study to Establish Biomarkers of Human Ageing
The Integrated Project MARK-AGE is performing a comprehensive and coherent Europe-wide population study aiming at the identification of powerful biomarkers of human ageing across a range of physiological systems. The work package ‘Oxidative Stress’ is under my supervision. Within this work package we will investigate the changes in (1) the oxidative stress status and (2) micronutrient levels during the aging process. Under my supervision is also the central Biobank of the project located at the University of Hohenheim. All blood, urine, and buccal mucosa specimens will be sent to the Biobank. Here the samples will be stored, aliquoted and distributed for analyses to be performed in the individual laboratories.
Irradiation induced protein damage
Support: Erwin Braun Foundation and various companies
Cells are often exposed to various irradiation sources. Such an exposure has various effects on cell physiology and metabolism. Often such changes are accompanied by modulations of the redox status of cells. We do have several ongoing studies on the effects of UV-A, infrared A or visible light in the photodynamic therapy.
Role of Protein Oxidation and Protein Aggregates in Aging and Neurodegeneration
Support: Various foundations and companies
Protein oxidation and aggregation seems to be a common feature of several neurodegenerative diseases and to some extent of physiological aging. It is not always clear why protein aggregation takes place, but a disturbance in the homeostasis between protein synthesis and protein degradation seems to be important. The result of this disturbance is the accumulation of modified proteins, which have various effects on the metabolism of affected cells.
COST B35 Action:
Lipid Peroxidation Associated Disorders
Support: EU
European Cooperation in the field of Scientific and Technical Research
Lipid peroxidation in biomedical science is a highly multidisciplinary topic involving research from chemistry through biochemistry, physiology and biotechnology to clinical sciences. This COST action aims to improve methods for detection and quantitation of lipid peroxidation, to determine the prevalence of lipid peroxidation products in various inflammatory diseases and its correlation to disease severity or outcome, to elucidate the metabolism of lipid peroxidation products and their proinflammatory effects, and develop and test novel antioxidants.