Cel
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.
Dziedzina nauki
Temat(-y)
Zaproszenie do składania wniosków
FP7-PEOPLE-2009-IEF
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IEF - Intra-European Fellowships (IEF)Koordynator
EH8 9YL Edinburgh
Zjednoczone Królestwo