TRYPCARPINTERACTORS

Uncovering the components and interactors of a novel cAMP signalling pathway and characterisation of its role in cytokinesis in Trypanosoma brucei

Coordinatore	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN    more  Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 contact info Titolo: Prof. Nome: Michael Cognome: Boshart Email: send email Telefono: +49 89 2180 74600 Fax: +49 89 2180 74629
Nazionalità Coordinatore	Germany [DE]
Totale costo	168˙794 €
EC contributo	168˙794 €
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-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2016-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN  Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 contact info Titolo: Prof. Nome: Michael Cognome: Boshart Email: send email Telefono: +49 89 2180 74600 Fax: +49 89 2180 74629	DE (MUENCHEN)	coordinator	168˙794.40

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 Obiettivo del progetto (Objective)

'This research project will focus on identifying the components of a remarkably divergent cyclic-AMP signalling cascade in the medically important, pathogenic protozoan Trypanosoma brucei. It will map an interaction network for this unique cAMP pathway and biochemically characterise the lethal effect on cytokinesis that disruption of the intracellular cAMP concentration has on the human-infective form of the parasite. Recently, cAMP metabolism was validated genetically and pharmacologically as an excellent drug target against Trypanosoma brucei: The cAMP-synthesizing adenylyl cyclases of the parasite were shown to be essential for cytokinesis of mother and daughter cells. Similarly, knockdown of phosphodiesterase enzymes (that degrade cAMP) kill the parasite, causing a severe cytokinesis defect. Finally, a newly identified trypanosomal-specific PDE inhibitor, Cpd A, is lethal to the parasite and also results in the same severe cytokinesis phenotype. How changes to cAMP concentrations translate to a cytokinesis defect and the identity of the downstream cAMP effector proteins in trypanosomes remain almost entirely unknown. To rectify this, a newly-developed forward genetics approach was used by the applicant to identify four cAMP response proteins (CARPs) which, when knocked down, give resistance to elevated cAMP and appear to represent part of a Kinetoplastid-specific cAMP pathway. The proposed research project will utilise advanced proteomic and interactomic techniques, combined with optogenetics, high-resolution live-cell confocal fluorescence microscopy and microscale thermophoresis to identify, map and characterize the proteins interacting with CARPs. These investigations will provide essential information on the evolution of the cAMP pathway in eukaryotic organisms and is likely to identify proteins unique to trypanosomes that will represent excellent future drug targets.'