Structural destabilization as a trigger for hereditary disease
|Main area:||Molecular biology|
|Target group:||Molecular Biomedicine, Biochemistry, Biology|
|Educational level:||Masters, Bachelor|
Our cells are equipped with an efficient protein quality control system, which functions to clear the cell misfolded proteins by targeting them for degradation via the ubiquitin-proteasome system. However, evidence suggests that this quality control system operates by following a better-safe-than-sorry principle. Hence, proteins which are only slightly misfolded and still retain function are also degraded. Accordingly, for certain hereditary diseases, abnormal, but functional, protein variants are degraded leading to the proteins activity being lost in the cells, which then in turn triggers the disease. In a series of related projects we propose to explore the specificity of the quality control system and its relevance for a number of hereditary diseases, including certain cancer predisposition syndromes and neuronal disorders. The obtained results may provide the important first steps towards novel therapeutic approaches to these and other genetic diseases. The projects will involve genetic, biochemical and molecular biological techniques including co-immunoprecipitation, Western blotting, and various high throughput screening methods, along with various cell biological techniques, such as pulse-chase experiments and fluorescence microscopy. The projects are available primarily at the Masters or Ph.D. level. For more specific detail, contact Rasmus Hartmann-Petersen for an informal meeting.
|Methods used:||Protein chemistry, Cell biology, Molecular Biology, Genetics|
|Keywords:||disease, degradation, folding, proteasome, genetics|
|Project home page:||http://www1.bio.ku.dk/english/research/bms/research/pbg/groups/rhp/|