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Assembly and host interactions of influenza virus polymerase in the living cell

Objective

Currently circulating highly pathogenic avian influenza virus strains (H5N1) could cause a devastating pandemic if they became transmissible between humans. Thus understanding of the mechanisms whereby influenza virus adapts from avian to mammalian hosts is of great significance. Recent studies have highlighted the importance for transmissibility of mutations in the viral polymerase - a trimeric complex possessing activities essential for transcription and replication of the viral RNA. The mechanism of polymerase assembly and the host factors involved are not clear yet, nor are the molecular functions affected by the mutations related to avian-to-mammal transmission. To clarify these and to complement the extensive studies of atomic resolution structure of the polymerase and its host-specific variants performed in the Host laboratory, we propose to investigate in living cells the intracellular trafficking, assembly and interactions with host cell factors of the human and avian variants of the polymerase subunits. State-of-the-art two-colour fluorescence cross-correlation spectroscopy (FCCS) and confocal microscopy techniques will be used to monitor these phenomena in a non-invasive way. The project is inter-disciplinary as it combines advanced cell biophysics with structural and molecular biology in order to address a very topical issue in virology. The results will contribute to understanding of the relationships between the atomic structure of influenza virus polymerase and its function in the infected cell. New insight into adaptation of the influenza virus replication machinery to mammalian hosts can be used to elaborate new strategies for development of anti-viral compounds targeting polymerase or its interactions with host cell factors. Pursuing this multidisciplinary project in a prestigious international environment and learning state-of-the-art techniques will provide the applicant an excellent training for a future independent research position

Field of science

  • /natural sciences/biological sciences/molecular biology
  • /natural sciences/physical sciences/optics/microscopy/confocal microscopy
  • /medical and health sciences/health sciences/infectious disease/RNA virus/influenza
  • /natural sciences/biological sciences/microbiology/virology
  • /natural sciences/biological sciences/genetics and heredity/mutation

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany
Activity type
Research Organisations
EU contribution
€ 150 103,51
Administrative Contact
Stephen Cusack (Dr.)