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Specific molecular mechanisms as targets for novel anti-parasitic drugs (SMMAD)
Start date: 01 Sep 2007, End date: 31 Mar 2008 PROJECT  FINISHED 

The complete set of genes of the nuclear genome of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, can now be exploited in the search of new drugs to fight American trypanosomiasis.In this context, the work plan of this fellowship b rings together the proteomic expertise and facilities of the Institute Cochin with the expertise of Dr. Mariano J. Levin in the field of T.cruzi gene structure, expression and RNA processing, in an attempt to validate protein-protein interactions involved in essential steps of the T.cruzi spliceosomal assembly as targets for novel anti-parasitic therapeutic interventions.Accordingly, the initial goal of this proposal is to identify the complete set of proteins of the early splicing complex (E complex) and the pre-splicing complex A of the T.cruzi spliceosome, and map protein-protein interactions using yeast two hybrid techniques.This should lead in turn,- to build a protein- protein interaction map of the early and presplicing complexes of the pretrans-spliceosome of the parasite,- to detect T.cruzi specific and essential interactor pairs,- to use these protein-protein interactions as targets of screenings for RNA processing blocking compounds and- to test their trypanomicidal effect.
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