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Dihydrofolate reductase-thymidilate synthase - drug target in trypanosoma cruzi

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Trypanosoma cruzi is the aetiological agent of Chagas' disease and according to WHO, approximately 20 million persons are currently afflicted in South America. Nevertheless, except for a few major findings, the advances in the treatment of Chagas' disease are moderate. Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are targets for chemotherapy, as inhibition of either enzyme results in the death of cells. The applicant will perform extended studies on the
bifunctionalTrypanosoma cruzi DHFR-TS and the individual DHFR domain. The first objective will consist in the improvement of the expression system for these proteins in order to initiate crystallization studies for performing drug design. The second main objective of the research project will be extensive mutagenesis of T. cruzi DHFR-TS. Hopefully the identification and exploitation of the clear differences between DHFRs from the parasite and its mammalian host should allow for the development of effective drugs.

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RGI - Research grants (individual fellowships)

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CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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