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CSB Core Faculty
| Hassane MchaourabSpectroscopic and biochemical studies of protein structure and functional dynamics
Small heat-shock proteins, including the major protein component in the lens alpha-crystallin, are molecular chaperones that help other proteins avoid aggregation. Protein aggregation is associated with many pathogenic conditions including alzheimer's diseases, mad cow disease and cataract. Our laboratory has pionnered novel assay to understand the mechanisms of both inherited and age-relted cataract.We investigate small heat-shock proteins from various organisms across the evolutionary spectrum. Active drug extrusion by multidrug transporters is one of four general mechanisms associated with the multidrug resistance phenomenon, a key problem in the treatment of bacterial and fungal infections and cancers. The overexpression of adenosine triphosphate binding cassette (ABC) transporters is the most frequent cause of resistance to cytotoxic agents. In addition, mutations in the genes encoding the 48 human ABC transporters are associated with diseases such as cystic fibrosis, Tangier disease and adrenoleukodystrophy. Our laboratory is investigating how these transporters work, a key step in the design of therapeutic strategies. Because many questions, both of structural and dynamic nature, cannot be answered with current physical techniques, we have been actively developing alternative structural methods based on paramagnetic and fluorescent reporter groups, taking advantage of the ability to site-specifically incorporate these groups into protein sequences. | ||||||||||||||||||||||||||||||||
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