Strukturella studier på amyloida proteiner samt på proeiner involverade i bakterie-värdcell interaktioner

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http://umu.diva-portal.org/smash/project.jsf?pid=project:1213

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Title [sv]

Exploring Mechanisms for Amyloid Formation and Bacteria-Host Cell Interactions

Title [en]

Strukturella studier på amyloida proteiner samt på proeiner involverade i bakterie-värdcell interaktioner

Abstract [sv]

The human plasma protein transthyretin (TTR) is normally a soluble protein that functions as transport protein for thyroxin. However, point-mutations in the human protein lead to structural changes and cause familial amyloidotic polyneuropathy (FAP, type I, Skelleftesjukan). The aim of our work is to characterize in detail the structural changes in the TTR protein that lead to amyloid formation and disease. Furthermore, in collaboration with the Swedish core platform Laboratories for Chemical Biology Umeå (LCBU) we perform a fragment based drug design search for new inhibitors of TTR self-assembly. So far more than 80 fragments have been identified and are ready for structural analysis using X-ray crystallographic techniques. In parallel, we also plan to perform a study where the allosteric effect of inhibitor binding to TTR will be investigated. Structure-function studies of proteins and protein complexes involved in bacteria host-cell interactions are also pursued. Proteins of interest include metalloproteases from Vibrio cholera, regulatory transcription factors for uropathogenic (UPEC) E. coli bacteria, and protein components from the type III secretion system from Yersinia pseudotuberculosis. For these and other studies, Small Angle Xray Scattering (SAXS) techniques and other biophysical methods are regularly used to complement our crystallographic studies.

Principal InvestigatorSauer-Eriksson, Elisabeth Umeå University

Coordinating organisation

Umeå University

Funder

Vetenskapsrådet

Period

2013-01-01 － 2015-12-31

National Category

Medicinal ChemistryCell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)