Our research
Our model organelle, among others, is the peroxisome. Peroxisomes contribute to several disease-relevant metabolic pathways in mammals (e.g., hydrogen peroxide metabolism, generation and scavenging of reactive oxygen species, break-down of fatty acids by beta-oxidation, and synthesis of ether phospholipids, which are important constituents of myelin sheaths) and have been associated with developmental processes, oxidative stress, ageing and neurodegeneration. In mammalian cells peroxisomes can easily be visualized by peroxisome-targeted fluorescent fusion proteins. Peroxisomes can be enriched and isolated from soft tissues and cells, and are biochemically accessible. Their high plasticity, the pharmacological (environmental) stimulation of their proliferation, and the defined morphological alterations during proliferation make them ideal model organelles with an interesting biology (for an overview see Islinger M, Grille S, Fahimi HD and Schrader M. (2012) The peroxisome - an update on mysteries. Histochem Cell Biol. 137, 547–574).
The investigation of peroxisome morphology and dynamics has become an exciting new field in cell biology and biomedical sciences because of its relation to organelle functionality and its impact on developmental and physiological processes.
Current research addresses the following fundamental biological questions by combining cell and molecular biology, biochemistry, microscopy, bioinformatics, and cell physiology.
The investigation of peroxisome morphology and dynamics has become an exciting new field in cell biology and biomedical sciences because of its relation to organelle functionality and its impact on developmental and physiological processes.
Current research addresses the following fundamental biological questions by combining cell and molecular biology, biochemistry, microscopy, bioinformatics, and cell physiology.
Hear about our research
SciPod have generated an audio version of our Scientia article, "Peroxisomes on the Rise". You can listen to it here, or click on the audio player to the right (~20 min). |
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1. How do peroxisomes form, multiply and distribute, and how does this contribute to cell physiology and disease?
Unraveling the peroxisomal growth and division machinery: We have identified the first components of the peroxisomal division machinery in mammalian cells and presented evidence that peroxisomal growth and division is a multistep process involving peroxisome membrane deformation, elongation, constriction and final division. The functional characterization, interplay and regulation of the molecular components represent a major challenge. New disorders based on defects in the molecular machinery have been discovered.
Unraveling the peroxisomal growth and division machinery: We have identified the first components of the peroxisomal division machinery in mammalian cells and presented evidence that peroxisomal growth and division is a multistep process involving peroxisome membrane deformation, elongation, constriction and final division. The functional characterization, interplay and regulation of the molecular components represent a major challenge. New disorders based on defects in the molecular machinery have been discovered.
2. How is the proliferation of peroxisomes regulated?
Regulation of peroxisome dynamics and abundance: There is particular interest in understanding how peroxisome dynamics and proliferation are regulated and how these processes might contribute to pathological conditions.
Regulation of peroxisome dynamics and abundance: There is particular interest in understanding how peroxisome dynamics and proliferation are regulated and how these processes might contribute to pathological conditions.
3. How do peroxisomes and other subcellular organelles co-operate to maintain cellular functions?
The peroxisome-mitochondria connection: We provided first evidence that peroxisomes and mitochondria share components of their division machinery indicating that both organelles exhibit a much closer interrelationship than previously appreciated. Thus, peroxisomal alterations in metabolism, biogenesis, dynamics and proliferation can potentially influence mitochondrial functions, and vice versa. This is of cell biological and clinical importance.
The peroxisome-ER connection: We discovered the first molecular mechanism for establishing peroxisome-ER (endoplasmic reticulum) interactions in mammalian cells and reported a new function for the acyl-CoA binding proteins ACBD5 and ACBD4 in peroxisome-ER tethering. Peroxisome-ER associations impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, peroxisome biogenesis, positioning and movement.
4. Furthermore, we are interested in the biogenesis of zymogen granules. These are sorting and secretion organelles of acinar cells in the exocrine pancreas, which contain our digestive enzymes. Their malfunction can result in pancreatitis.
The peroxisome-mitochondria connection: We provided first evidence that peroxisomes and mitochondria share components of their division machinery indicating that both organelles exhibit a much closer interrelationship than previously appreciated. Thus, peroxisomal alterations in metabolism, biogenesis, dynamics and proliferation can potentially influence mitochondrial functions, and vice versa. This is of cell biological and clinical importance.
The peroxisome-ER connection: We discovered the first molecular mechanism for establishing peroxisome-ER (endoplasmic reticulum) interactions in mammalian cells and reported a new function for the acyl-CoA binding proteins ACBD5 and ACBD4 in peroxisome-ER tethering. Peroxisome-ER associations impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, peroxisome biogenesis, positioning and movement.
4. Furthermore, we are interested in the biogenesis of zymogen granules. These are sorting and secretion organelles of acinar cells in the exocrine pancreas, which contain our digestive enzymes. Their malfunction can result in pancreatitis.
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