Objective
We propose to develop novel drug leads for the therapy of the major human parasitic disease, schistosomiasis, using a holistic approach that will enable us to progress from the cloned target protein to the lead compound and from epigenetic inhibitors to crucial targets. For this, we have chosen to target the histone modifying enzymes (HME); histone deacetylases (HDAC), histone acetyltransferases (HAT), histone methyltransferases (HMT) and histone demethylases (HDM) of Schistosoma mansoni. In the course of the project the members of HDAC classes I, II and III (sirtuins) HAT, HMT and HDM encoded in the genome will be identified. In parallel, a reverse chemical genetics approach using generic inhibitors of HME subclasses available within the consortium in cultures of schistosome larvae will identify those classes that are bona fide drug targets. These enzymes will be validated as therapeutic targets individually or collectively using RNAi to invalidate the corresponding genes. Potential inhibitors (HDACi, HATi, HMTi, HDMi) will be screened by in silico docking to the modelled catalytic domains of the enzymes and collections of analogues will be tested for their ability to inhibit the activity of the corresponding recombinant proteins in high-throughput assays. We will also establish gene expression profiles corresponding to HME invalidation (by RNAi) and inhibition (using drug candidates in cultured larval stages (schistosomula) that will enable the determination of the specificity of action of the drugs. Finally, in vivo testing of the best candidates will be done in infected mice. In this way, during the study period we aim to develop a series of candidate molecules that can progress to clinical trials.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-HEALTH-2009-single-stage
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.