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Targeting Protein Synthesis in the Apicoplast and Cytoplasm of Plasmodium (MEPHITIS)
Start date: 01 Jan 2009, End date: 30 Jun 2012 PROJECT  FINISHED 

"The protein synthesis machinery represents one of the most useful targets for the development of new anti-infectives. Several families of broadly used antibiotics (tetracyclines, macrolides, and novel glycopeptides like vancomycin, among others) exert their function by blocking the protein synthesis machinery. Doxicycline, a tetracycline antibiotic, remains a useful tool for the prevention of paludism among travellers, despite its numerous secondary effects. And yet, very little is known about the specifics of the protein synthesis machinery in Plasmodium. A search of articles in the PubMed library with the words Plasmodium and ribosome/ribosomal in their titles will yield 6 publications since the year 2000. Only one article contains the words tRNA (or transfer RNA) and Plasmodium in its title, in the same period. And only one article in PubMed (Snewin et al., 1996) contains the words Plasmodium and ‘tRNA synthetase’ (or ligase) in its title. This lack of information about this central metabolic pathway in Plasmodium clearly blocks the possibility of transferring the knowledge in protein synthesis to the development of new anti-malarial drugs directed against the translational machinery of the parasite. Thus, the study of components of the genetic code in Plasmodium has the potential for providing new and important information on the biology of the parasite and, more importantly, open new leads for the development of novel anti-malarials. This proposal coordinates an effort to study tRNA biology in Plasmodium falciparum. It contains specific schemes for the development of new pharmacological screens, several initiatives for the selection of new potential anti-malarial drugs, and projects designed to answer fundamental questions regarding protein synthesis in Plasmodium. The laboratories in MEPHITIS accumulate a large body of experience in the biology of this parasite, and in different aspects of tRNA biology in model species."
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