Conformational changes in bio-molecules are closely linked to their function and thus of major interest for an understanding of many biological processes. For a number of biologically active RNA molecules there are indications from biochemical assays that they are able to regulate their function by switching between different conformations of similar energetic stability. An important example is the RNA genome of the Human Immunodeficiency Virus (HIV), which is responsible for the AIDS disease, one of the mo st serious pandemics ever caused by a virus. Despite an intensive research effort the ultimate vaccine or drug against this disease has not yet been successfully developed. The difficulty related to this can be explained by the extraordinary high rate of g enetic evolution of the RNA genome, which is related to a high mutation rate and a tendency of the RNA molecules to form dimers. The mechanism by which dimerization is initiated and regulated in the viral life cycle is not very well understood but is belie ved to be mediated by conformational changes in the RNA. The objective of the present project is to address in detail this issue with a new experimental technique, single-molecule fluorescence-resonance-energy-transfer (FRET) microscopy, which promises im portant new knowledge that cannot be obtained with traditional, ensemble-averaging methods. The activity proposed here is very much in line with the objectives of the Marie Curie Actions, implying the transfer of knowledge and promotion of European scienti fic excellence, and depending on interdisciplinary collaborations at the national and European levels. Furthermore, it can be classified as nanoscience as well as life science and biotechnology, all of which are declared priority levels of the European Com mission.
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