Objectif
The project plans a multi-lateral cooperation involving two Russian (Moscow and Pushchino) and two Western (Dutch and Finnish) groups and is aimed at investigation of some fundamental and applied aspects of reproduction and evolution of viruses with positive RNA-strand genome. For 3 of these groups the proposal is a continuation of previous successful INTAS grants (95-1365 and 97-10348). Picornaviruses (polioviruses, coxsackieviruses, parechoviruses) and Q(phage will be used as experimental objects. Multidisciplinary approach including biochemical, biophysical, morphological, and chemical techniques as well as genetic engineering and bioinformatics will be implemented.
The following main issues will be addressed
(a) The effects of picornavirus infection on the expression of the host cell genome and on the infrastructure of infected cells. To this end, the global mRNA expression in cells infected with different picornaviruses under different conditions will be studied by cDNA microchip technology and attempts to identify key host genes involved in the defensive and pathological reactions will be undertaken. The mechanisms of alteration of intracellular trafficking (including the changes in protein distribution among the nuclear and cytoplasmic compartments, recently discovered by an applicant) will be investigated;
(b) The factors controlling implementation of the defensive responses to viral infection. In particular the steps that couple viral components with upstream apoptotic reactions (e. g., such as activation of initiating caspases) will be investigated. Contribution of cell-specific difference in the balance of proapoptotic and antiapoptotic factors to the character of the response to picornavirus infection will be studied;
(c) The structure/function relationships in replicative (oriL, oriR, cre) and translational (IRES) cis-acting elements of picornavirus genomes. In particular, a new approach to elucidation of the structural stringency of the apparently conserved control elements will be exploited: either individual motifs or entire elements will be replaced, in the full-length viral genomes, by random sequences followed by selection and analysis of viable progeny. Also physical methods (e. g., NMR) will be used to solve the complex structure of the regulatory elements;
(d) The mechanisms and biological significance of recombination between RNA molecules. Special attention will be paid to the mechanism of nonreplicative RNA recombination recently discovered by the applicants. The mechanisms of cleavage and ligation of the RNA fragments will be studied. Occurrence and significance of natural recombination between picornaviruses will be studied by both sequencing of genomes of circulating viruses and by analysis of sequence databases;
(e) Development of new tools for RNA analysis in evolutionary and molecular epidemiological studies. In particular, an RT-PCR version of the molecular colony technique recently worked out by one of the applicant will be further developed and adapted for studying recombination between any viral and/or cellular RNAs. Possible advantages of cDNA microarray technique for fast and precise characterization of the genomes of circulating polioviruses will be evaluated.
The advantage of the proposed cooperation consists in using diverse experimental objects to check the generality of the conclusions made; using diverse approaches to the solution of the same problem, and sharing expertise, resources and ideas. The collaborative investigations, which have already been carried out, proved to be successful, as judged by the importance of the results obtained and published in high ranked journals. As the experience shows, such a collaborative program adds significantly to the progress of the research of each participating group.
Programme(s)
Programmes de financement pluriannuels qui définissent les priorités de l’UE en matière de recherche et d’innovation.
Programmes de financement pluriannuels qui définissent les priorités de l’UE en matière de recherche et d’innovation.
Thème(s)
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Les appels à propositions sont divisés en thèmes. Un thème définit un sujet ou un domaine spécifique dans le cadre duquel les candidats peuvent soumettre des propositions. La description d’un thème comprend sa portée spécifique et l’impact attendu du projet financé.
Appel à propositions
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Procédure par laquelle les candidats sont invités à soumettre des propositions de projet en vue de bénéficier d’un financement de l’UE.
Régime de financement
Régime de financement (ou «type d’action») à l’intérieur d’un programme présentant des caractéristiques communes. Le régime de financement précise le champ d’application de ce qui est financé, le taux de remboursement, les critères d’évaluation spécifiques pour bénéficier du financement et les formes simplifiées de couverture des coûts, telles que les montants forfaitaires.
Régime de financement (ou «type d’action») à l’intérieur d’un programme présentant des caractéristiques communes. Le régime de financement précise le champ d’application de ce qui est financé, le taux de remboursement, les critères d’évaluation spécifiques pour bénéficier du financement et les formes simplifiées de couverture des coûts, telles que les montants forfaitaires.
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Coordinateur
6500 HB Nijmegen
Pays-Bas
Les coûts totaux encourus par l’organisation concernée pour participer au projet, y compris les coûts directs et indirects. Ce montant est un sous-ensemble du budget global du projet.