Verknüpfung von Struktur und Funktion einzelner Viruspartikel

• Antragstellerin: Dr. Evelyn Plötz
• Fachliche Zuordnung: Biophysik ; Virologie
• Förderung: Förderung von 2013 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 238802862

Viruses are a worldwide public health hazard, but despite their importance, many aspects of their infection mechanisms are still poorly understood. For example, the complex pathogenicity of dengue virus (DENV) has, so far, prohibited vaccine development in spite of a significant impact of DENV on millions of people every year. One reason is that structural information, such as size, morphology, or the arrangement of surface proteins (e.g., scaffold formation or clustering), can only be obtained using demanding methodology, such as high-resolution electron-microscopy (EM) and that the obtained information cannot be directly linked to virus pathogenicity of the very same particles. However, for DENV it is proposed that number and surface assembly of the different proteins decide upon the degree of infectivity of each individual virus.In this proposal, we aim to develop a single-particle-based optical toolkit to establish a direct link between the structure and function of viruses.aim i: To make this experimentally possible, we will develop the so-called virus PAINT (vPAINT) imaging technique that uses fluorescence-based super-resolution imaging to create optical images of virus. vPAINT images will provide direct information on virus size, morphology and distribution of membrane-embedded proteins. vPAINT will complement EM techniques by providing optical images of virus particles with nanometre resolution. Notably, these vPAINT images can be of dynamic nature and are obtained under live-cell-compatible conditions, i.e., without staining, freezing, sectioning and without requirements for symmetry.aim ii: With this novel toolkit we will answer outstanding questions about the functional importance of DENV maturation for pathogenicity by directly linking virus maturation to infectivity, i.e. by linking the distribution and number of membrane-embedded proteins (viral structure), to the ability for membrane fusion (virus functionality).

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Niederlande
• Gastgeber: Professor Dr. Thorben Cordes