Objetivo Bacterial infections represent a major and global health problem, which is further aggravated by the rapid and ongoing increase in antibiotic resistance. The limited success in the development of targeted therapies for particular invasive strains can be attributed to our limited knowledge how pathogens modulate their proteome homeostasis in vivo, knowledge that has so far remained elusive due to technical limitations.Here I propose the use of proteome-wide selected reaction monitoring mass spectrometry (SRM-MS) for pathogen proteome profiling from samples obtained directly from in vivo using group A streptococci (GAS) as a model system. The proposal describes the use of SRM-MS to facilitate the construction of comprehensive and quantitative molecular anatomy knowledge models outlining spatial organization, pathway organization, absolute protein concentration estimations and interaction partners with host for complete microbial proteomes. Using the molecular anatomy as benchmark I intend compare how the proteome homeostasis is controlled in pathogens isolated directly from patients with different degree of disease severity to understand how disease severity, anatomical location and host dependencies effects the proteome homeostasis.The outlined proposal describes a generic strategy to provide comprehensive understanding of the pathogen adaption directly in vivo and represents a paradigm shift in the field of bacterial infectious disease. This proposal addresses central aspects within the medical microbiology field that has been long sought for but never studied due to technology limitations and will influence the development of the next generation targeted vaccine and therapeutic development programs. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesbasic medicineanatomy and morphologynatural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistancemedical and health sciencesbasic medicinephysiologyhomeostasis Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2012-StG_20111109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida LUNDS UNIVERSITET Aportación de la UE € 1 498 699,00 Dirección Paradisgatan 5c 22100 Lund Suecia Ver en el mapa Región Södra Sverige Sydsverige Skåne län Tipo de actividad Higher or Secondary Education Establishments Investigador principal Anders Johan Malmström (Dr.) Contacto administrativo Anita Berglund (Mrs.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo LUNDS UNIVERSITET Suecia Aportación de la UE € 1 498 699,00 Dirección Paradisgatan 5c 22100 Lund Ver en el mapa Región Södra Sverige Sydsverige Skåne län Tipo de actividad Higher or Secondary Education Establishments Investigador principal Anders Johan Malmström (Dr.) Contacto administrativo Anita Berglund (Mrs.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
