NOVSEC-TB

Novel secretion systems of Mycobacterium tuberculosis and their role in host-pathogen interaction

Coordinatore	INSTITUT PASTEUR    more  Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Dr. Nome: Nadia Cognome: Khelef Email: send email Telefono: +33 1 40 61 33 78 Fax: +33 1 40 61 39 40
Nazionalità Coordinatore	France [FR]
Totale costo	3˙762˙443 €
EC contributo	2˙821˙726 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2007-A
Funding Scheme	CP-FP
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-01-01   -   2011-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT PASTEUR  Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Dr. Nome: Nadia Cognome: Khelef Email: send email Telefono: +33 1 40 61 33 78 Fax: +33 1 40 61 39 40	FR (PARIS CEDEX 15)	coordinator	0.00
2	ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE  Organization address address: BATIMENT CE 3316 STATION 1 city: LAUSANNE postcode: 1015 contact info Titolo: Dr. Nome: Iain Cognome: Old Email: send email Telefono: +41 21 6931794 Fax: +41 21 6931790	CH (LAUSANNE)	participant	0.00
3	SOUTH AFRICAN MEDICAL RESEARCH COUNCIL  Organization address address: Francie van Zijl Drive - Parowvalley city: TYGERBERG postcode: 7505 contact info Titolo: Mr. Nome: Philip Cognome: Du Plessis Email: send email Telefono: +27 21 938 0481 Fax: +27 21 938 0564	ZA (TYGERBERG)	participant	0.00
4	UNIVERSITA CATTOLICA DEL SACRO CUORE  Organization address address: Largo Agostino Gemelli 1 city: MILANO postcode: 20123 contact info Titolo: Mr. Nome: Filippo Cognome: Leone Email: send email Telefono: +39 630 156 099 Fax: +39 630 156 803	IT (MILANO)	participant	0.00
5	UNIVERSITA DEGLI STUDI DI PADOVA  Organization address address: VIA 8 FEBBRAIO 2 city: PADOVA postcode: 35122 contact info Titolo: Prof. Nome: Giorgio Cognome: Bressan Email: send email Telefono: 39 049 8272350 Fax: 39 049 8272355	IT (PADOVA)	participant	0.00
6	UNIVERSITA DI PISA  Organization address address: Lungarno Pacinotti 43/44 city: PISA postcode: 56126 contact info Titolo: Prof. Nome: Gaetano Cognome: Privitera Email: send email Telefono: +39 050 2213573 Fax: +39 050 2213575	IT (PISA)	participant	0.00
7	UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN  Organization address address: BELFIELD city: DUBLIN postcode: 4 contact info Titolo: Mr. Nome: Donal Cognome: Doolan Email: send email Telefono: +35 317 161656 Fax: +35 317 161216	IE (DUBLIN)	participant	0.00
8	VRIJE UNIVERSITEIT MEDISCH CENTRUM  Organization address address: De Boelelaan 1117 city: AMSTERDAM postcode: 1007 MB contact info Titolo: Ms. Nome: Sylvia Cognome: Tromp Email: send email Telefono: +31 20 4443100 Fax: +31 20 4443670	NL (AMSTERDAM)	participant	0.00

Mappa

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 Obiettivo del progetto (Objective)

'Tuberculosis is a major public health threat to the populations of Europe and the world. Mycobacterium tuberculosis, the etiological agent of the disease, can multiply and persist within phagocytic cells and this early event is of primary importance for the outcome of the infection. The main objectives of this proposal are to use highly innovative approaches in molecular and cell biology, biochemistry, immunology and imagery to elucidate the function and interplay of three families of immunogenic proteins of M. tuberculosis, the ESX, PE and PPE families. It was recently found that the ESX systems constitute novel secretion machineries that export major virulence factors and important diagnostic and protective antigens. While the ESX-1 system is responsible for the secretion of the prototypic ESX proteins, namely, the 6 kDa early secreted antigenic target (ESAT-6) and the 10 kDa culture filtrate protein (CFP-10), which are the most important proteins of M. tuberculosis involved in host-pathogen interaction, ESX-5 is implicated in the secretion of PE/PPE proteins. Restriction to pathogenic mycobacteria makes them highly interesting targets for host-pathogen interaction. The ESX-3 system appears to be essential. Thus, in this project we propose to --> analyse the global gene expression network of ESX-1, ESX-3 and ESX-5, --> determine the nature and diversity of the effector proteins they secrete, --> establish their mode of action and sub-cellular localisation, --> survey potential genetic variation in clinical isolates, --> assess their interaction with the immune system of the host, --> evaluate the suitability of ESX systems as drug targets, --> screen small molecules for their potential to inhibit ESX-mediated secretion. The proposed approach will generate major insights into the role of these proteins in pathogenicity that are of utmost importance for the development of new diagnostics, vaccines and therapeutic agents for tuberculosis prevention and control.'