Obiettivo
Bacterial infection is the major cause of disability and death in children worldwide. We will use meningococcal disease (MD) as a model to understand genetic factors underlying susceptibility and severity of childhood bacterial infection which will then be applied to other childhood infections. We have established cohorts of patients with MD in Central and Southern Europe (CE,SE), UK and Africa as well as cohorts with other bacterial infections. We have established an inter-disciplinary team with expertise in Infectious Diseases, Immunogenetics, Bio-informatics, Microbiology, Public Health and Vaccinology including SME and industrial partners. We have already undertaken a genome wide study (GWAS) to identify genes causing susceptibility to meningococcal disease in a UK cohort. We identified complement factor H (fH) and fH-related (fHr) genes controlling MD susceptibility. This finding is fundamental to prevention as vaccines containing the MD fH receptor are undergoing trials. We will undertake GWAS on the CE, and SE MD cohorts, allowing meta analysis, and cross validation, and undertake GWAS on 2,500 Meningococcal Vaccine recipients. We will use next generation sequencing to identify the causal variants within the fH/fHr region and other regions implicated by pathway and severity analyses of the three MD GWAS and vaccine GWAS. We will match bacterial and host genetic variation and identify mechanisms of action of fH variants and other genes controlling susceptibility and severity using RNA expression, functional analyses and animal models. We will identify Mendelian defects and rare mutations as well as copy number variation and epi-genetic effects using next generation sequencing and RNA sequencing in “extreme phenotype” cohorts with MD , pneumococcal ,staphylococcal and salmonella disease. The study will identify mechanisms underlying susceptibility, provide new targets for treatment and prevention, and identify those at risk of disease or poor outcome.
Campo scientifico
- medical and health scienceshealth sciencespublic health
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsRNA
Argomento(i)
Invito a presentare proposte
FP7-HEALTH-2011-two-stage
Vedi altri progetti per questo bando
Meccanismo di finanziamento
CP-IP - Large-scale integrating projectCoordinatore
SW7 2AZ LONDON
Regno Unito
Mostra sulla mappa
Partecipanti (15)
L69 7ZX Liverpool
Mostra sulla mappa
OX1 2JD Oxford
Mostra sulla mappa
1105AZ Amsterdam
Mostra sulla mappa
3015 GD Rotterdam
Mostra sulla mappa
6525 XZ Nijmegen
Mostra sulla mappa
8010 Graz
Mostra sulla mappa
15703 Santiago De Compostela
Mostra sulla mappa
138668 SINGAPORE
Mostra sulla mappa
OX5 PF OXFORD
Mostra sulla mappa
CV4 7EZ Coventry
Mostra sulla mappa
W1B 1AL LONDON
Mostra sulla mappa
53100 SIENA
Mostra sulla mappa
SW7 2AZ LONDON
Mostra sulla mappa
3012 Bern
Mostra sulla mappa
NE1 7RU Newcastle Upon Tyne
Mostra sulla mappa