PLASMODIUM MOTILITY

Dissecting cGMP- and calcium-dependent signalling pathways that control gliding of a malaria zoite

 Coordinatore GENOME RESEARCH LIMITED 

 Organization address address: THE GIBBS BUILDING, EUSTON ROAD 215
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Mr.
Nome: David
Cognome: Davison
Email: send email
Telefono: +44 1223 834244
Fax: +44 1223 494919

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 179˙603 €
 EC contributo 179˙603 €
 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 2011
 Periodo (anno-mese-giorno) 2011-07-01   -   2013-06-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    GENOME RESEARCH LIMITED

 Organization address address: THE GIBBS BUILDING, EUSTON ROAD 215
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Mr.
Nome: David
Cognome: Davison
Email: send email
Telefono: +44 1223 834244
Fax: +44 1223 494919

UK (LONDON) coordinator 179˙603.20

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

phenotyping    invade    ookinete    signalling    quantitative    motility    dependent    mutants    calcium    parasites    imaging    substrates    candidate    molecular    cgmp    gliding    malaria    pathways   

 Obiettivo del progetto (Objective)

'Malaria parasites critically depend on an unusual form of gliding motility to colonize their hosts and to invade cells. Transmission of malaria to the mosquito, for instance, relies on the ability of the motile zygote, the ookinete, to glide towards and invade the midgut epithelium. Results obtained in the host team have revealed a central role of cGMP- and calcium-dependent signalling in ookinete motility. Nevertheless, how these pathways control gliding is unknown. I therefore propose to combine real-time quantitative imaging approaches with molecular phenotyping of parasite phosphoproteins to identify and distinguish molecular targets of signalling through calcium and cGMP-dependent pathways in Plasmodium berghei ookinetes. For this purpose, I will use transgenic parasites in which cGMP- and/or calcium-dependent signalling pathways are either inactivated and/or deregulated. The impact of genetically inhibiting or over-stimulating specific protein kinases on motility will be analysed in an automated quantitative imaging assay, allowing signalling pathways to be linked with specific changes in motility phenotypes. I will then use shotgun phosphoproteomics on enriched populations of selected mutants to identify candidate substrates. Phenotyping of stage-specific mutants in candidate substrates will allow the molecular targets of signalling cascades to be verified.'

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