PARAMOTSIG

Receptor signalling mediating malaria parasite motility

 Coordinatore UNIVERSITAETSKLINIKUM HEIDELBERG 

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 Nazionalità Coordinatore Germany [DE]
 Totale costo 1˙453˙800 €
 EC contributo 1˙453˙800 €
 Programma 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)
 Code Call ERC-2011-StG_20101109
 Funding Scheme ERC-SG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-04-01   -   2017-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM HEIDELBERG

 Organization address address: IM NEUENHEIMER FELD 672
city: HEIDELBERG
postcode: 69120

contact info
Titolo: Dr.
Nome: Friedrich
Cognome: Frischknecht
Email: send email
Telefono: +49 6221 566537
Fax: +49 6221 564643

DE (HEIDELBERG) hostInstitution 1˙453˙800.00
2    UNIVERSITAETSKLINIKUM HEIDELBERG

 Organization address address: IM NEUENHEIMER FELD 672
city: HEIDELBERG
postcode: 69120

contact info
Titolo: Mr.
Nome: Thorsten
Cognome: Brietz
Email: send email
Telefono: +49 6221 567086
Fax: +49 6221 565460

DE (HEIDELBERG) hostInstitution 1˙453˙800.00

Mappa


 Word cloud

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

sporozoites    host    actin    motility    sporozoite    malaria    adhesion    assays    mechanisms    dependent    dynamic    adhesins    molecular    parasite    signalling   

 Obiettivo del progetto (Objective)

'Plasmodium sporozoites are the motile forms of the malaria parasite injected into the host by a mosquito. Sporozoite motility is essential for tissue penetration as well as host cell invasion and thus pathogenesis suggesting that blocking motility could potentially add a new way in controlling malaria. It is dependent on a parasite specific myosin, a highly divergent actin and plasma membrane proteins, adhesins that link the substrate to the actomyosin motor. We want to understand the molecular and biophysical basis that underlies the motility of sporozoites to eventually be able to block it. Consequently, we developed methods that allow a systematic probing of key variables important in motility in order to reveal the basic mechanisms of sporozoite locomotion and to screen for small molecules that inhibit motility. Using these assays, we made a number of groundbreaking observations on the cellular and molecular level that gave new insights into the mechanisms of sporozoite adhesion and motility. For example, the dynamic, actin-dependent turnover of adhesion sites was found to be a key factor in sporozoite motility. It is our ultimate goal to understand sporozoite motility to a degree that we can provide a comprehensive dynamic model of sporozoite movement. With the current proposal we aim at unravelling the initial molecular events leading to sporozoite motility focussing on three different adhesins that are known or suspected to be involved in motility. We hypothesize that outside-in signalling leading to actin rearrangements originates from the formation of homo- or heterodimers between these adhesins. Additionally we suggest that inside-out signalling contributes to modulation of adhesion strengths mediated by these adhesins. To test these hypotheses we will generate recombinant parasites that lack two adhesins or express fluorescently tagged adhesin fusions, chimeric or mutant adhesins and investigate these with our recently developed toolbox of novel assays.'

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