INFBIOSYS

THE ROLE OF BACTERIAL MULTIGENE FAMILIES IN INFECTION: IDENTIFICATION OF HOST TARGET NETWORKS BY HIGH-THROUGHPUT PROTEIN INTERACTOMICS

Coordinatore	THE UNIVERSITY OF EDINBURGH    more  Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL contact info Titolo: Ms. Nome: Angela Cognome: Noble Email: send email Telefono: +44 131 650 9024 Fax: +44 131 651 4028
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	173˙240 €
EC contributo	173˙240 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-IEF
Funding Scheme	MC-IEF
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-07-01   -   2012-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE UNIVERSITY OF EDINBURGH  Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL contact info Titolo: Ms. Nome: Angela Cognome: Noble Email: send email Telefono: +44 131 650 9024 Fax: +44 131 651 4028	UK (EDINBURGH)	coordinator	173˙240.80

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 Obiettivo del progetto (Objective)

'The genomes of pathogenic bacteria often contain multiple copies of genes with similar sequence. The encoded proteins are generally secreted or associated with the bacterial surface and are thus likely to be involved in the host-pathogen interaction. However, the functions of these multigene families in pathogenesis remain largely unknown. We will investigate the role of bacterial multigene family proteins in the host-pathogen interaction taking a Systems Biology-based approach. We will focus on two model pathogen-specific virulence-related proteins families: the Inl (internalin) proteins from the gram-positive genus Listeria, and the Vap (virulence-associated) proteins from Rhodococcus equi, a pathogenic actinomycete related to Mycobacterium tuberculosis (MTB). We will also investigate the Mce and PE/PPE proteins, which are distributed among several pathogenic actinobacteria including R. equi and MTB. Different members of these multigene families are found in genotypes or species differing in virulence and pathogenic tropism. Our hypothesis is that the specific multigene complements carried by the different “pathovars” contribute to their distinct pathogenic properties. We will address the research question by systematically identifying binding partners to the investigated proteins and relevant domains thereof by interaction proteomics using high-throughput yeast two-hybrid (Y2H) screens with large host (mammalian) cDNA prey libraries. We will then apply bioinformatics tools and network analysis to define the host subcellular compartments and functional networks and pathways targeted by the bacterial multigene family proteins, and the global contribution of the identified interactions to pathogenesis. Microbial surface-associated and excreted proteins are at the forefront of the host-pathogen interplay, mediating adherence/colonisation, subverting host pathways, or modulating innate or acquired immunity.'