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The genetic basis of meningococcal and other life threatening bacterial infections of childhood

Objective

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.

Call for proposal

FP7-HEALTH-2011-two-stage
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Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 838 599
Administrative Contact
Scott Wheatley (Mr.)

Participants (15)

THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 391 679
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Enitan Carrol (Dr.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 738 802
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Dr.)
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 796 799
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Salena Voorneman
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Netherlands
EU contribution
€ 417 962,40
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jan A. Hazelzet (Dr.)
STICHTING RADBOUD UNIVERSITEIT
Netherlands
EU contribution
€ 548 293
Address
Houtlaan 4
6525 XZ Nijmegen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Wim Van Oijen (Mr.)
MEDIZINISCHE UNIVERSITAT GRAZ
Austria
EU contribution
€ 796 800
Address
Auenbruggerplatz 2
8036 Graz
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Werner Zenz (Prof.)
SERVIZO GALEGO DE SAUDE
Spain
EU contribution
€ 1 195 200
Address
Edificio Administrativo San Lázaro
15703 Santiago De Compostela
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Federico Martinon-Torres (Dr.)
BIOMEDICAL SCIENCES INSTITUTES Limited by Guarantee
Singapore
EU contribution
€ 996 000
Address
Biopolis Way 20
138668 Singapore
Activity type
Research Organisations
Administrative Contact
Martin Lloyd Hibberd (Dr.)
OXFORD GENE TECHNOLOGY (OPERATIONS) Ltd
United Kingdom
EU contribution
€ 1 092 070
Address
Sandy Lane Begbroke Science Park Hirsch Building
OX5 1PF Yarnton Oxford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
James Clough (Mr.)
MICROPATHOLOGY LIMITED
United Kingdom
EU contribution
€ 599 592
Address
Sir William Lyons Road
CV4 7EZ Coventry
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Colin Grahammedical Director Fink (Dr.)
MEDICAL RESEARCH COUNCIL
United Kingdom
EU contribution
€ 599 710
Address
North Star Avenue Polaris House
SN2 1FL Swindon
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Kalifa Bojang (Dr.)
GLAXOSMITHKLINE VACCINES SRL
Italy
EU contribution
€ 298 775
Address
Via Fiorentina 1
53100 Siena
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Francesco Gulli (Dr.)
IC CONSULTANTS LTD
United Kingdom
EU contribution
€ 597 745
Address
Sherfield Building, Imperial College Of Science, Technology And Medicine
SW7 2AZ London
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Kornelia Jumel (Dr.)
UNIVERSITAET BERN
Switzerland
Address
Hochschulstrasse 6
3012 Bern
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christoph Aebi (Prof.)
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
EU contribution
€ 80 620,60
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Debra Mudditt (Mrs.)