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Title: Imaging inclusion bodies in cell models of Huntington’s and other related conformational diseases using full-field x-ray microscopy. Author(s): Philip Heraud1,2, David Cram1, Peter Guttmann3, Steve Bottomley4. Affiliations: 1. Monash Immunology and Stem Cell Laboratories, Monash University, Wellington Road, Clayton, Victoria, 3800 2. Centre for Biospectroscopy, Monash University, Wellington Road, Clayton, Victoria, 3800 3. Bessy II synchrotron, Albert-Einstein-Str. 15, 12489 Berlin, Germany 4. Department of Biochemistry, School of Biomedical Sciences, Monash University, Wellington Road, Clayton, Victoria, 3800 Contact email: [email protected] Protein conformational diseases such as Huntington’s Disease and spinocerebellar ataxias (SCA) are characterised by mutations of wild type genes leading to the expression of proteins that have expanded poly-glutamine domains. The expression of poly-Q mutant proteins results in the formation of intra-cytoplasmic and intra-nuclear inclusion bodies in cells. These are believed to result from misfolding of the poly-Q proteins in addition to the formation of beta-amyloid protein within the bodies. It is assumed that the accumulation of inclusion bodies in neurons results in neurodegeneration and clinical symptoms, however this link is far from being clearly understood. A major limitation in this area of research is the ability to image inclusion body formation, particularly at the early stages. Confocal fluorescence microscopy, which is the major tool presently employed, has a spatial resolution close to the size of fully formed inclusions. We have been investigating the use of full x-ray microscopy/tomography at beamline U41-TXM at Bessy II in Berlin to image inclusion bodies in various prokaryote and human cell models. Preliminary studies where SCA3 is expressed in E. coli bacteria will be presented.