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SUMMARY OF RESEARCH
Identification and characterization of regulatory and functional sequences contained in the Trypanosoma Cruzi L1Tc mobile element.
Long interspersed Elements-1 (LINE-1 or L1s) are abundant non-long terminal repeat (non-LTR) retrotransposons in mammalian genomes autonomously mobilized via a RNA intermediate through a mechanism that requires various enzymatic activities. The LINEs enzymatic machinery is, moreover, responsible for mobilization of SINEs although the enzymatic and functional characteristics of the enzymes encoded by LINEs are still unknown. Interestingly, the T. cruzi genome contains 30% of repeated sequences most of them SINEs and LINEs essential in the parasite?s biology.
Regarding to DNA mobile elements, our research is focused on the L1Tc non-LTR retrotransposons from Trypanosoma cruzi.
Transcription is the first step in mobilization of LINEs and consequently one of our objectives is to characterize and to analyze the functionality of the putative promoter sequence from the L1Tc LINE. In addition we are studying the enzymatic properties and functional requirements of the RT-RNaseH bifunctional protein encoded by the element as well as identifying and characterizing the sequence responsible for the nucleic acids chaperone activity and the nucleic acids binding capacity of C2-L1Tc protein.
Characterization of Leishmania and trypanosoma cruzi recombinant proteins as cellular markers of the situation, progression and control of Leishmaniosis in Leishmaniosis/HIV+ patients, and chagas´Disease.
Protozoan parasites from the genus Leishmania are etiological agents of a wide spectrum of human severe diseases known as leishmaniasis. In spite of there is an acquire immunity against Leishmania the infection rate is increasing especially in immunodepressed patients. Specific chemotherapy results inefficient and toxic and there is not an antileishmania vaccine. The illness control requires the induction of a multiple immune response against diverse and specific antigens of the parasite.
Our Resereach in this area is focused on to identify proteins and antigenic proteins whose properties make them good candidates for developing efficient immunotherapies against leishmaniosis. In this context we are producing DNA chimerical molecules composed by sequences coding for several proteins of Leishmania infantum associated to the immunomodulator molecule T-HSP70. The ability of these molecules to produce an efficient immune response against infection is being determined in mice. Protection assays against the parasite are also being carried out on the murine experimental system analyzing as infection parameters, the histological pattern and parasitemia level in target tissues (spleen and liver). The antigenic capacity (humoral and cellular) of the said recombinant proteins is also being tested in natural infection on sera and peripheral blood cells from HIV+/leishmaniasis patients.
The protozoan parasite Trypanosoma cruzi is the etiological agent causing Chagas? disease or American trypanosomiasis, now ranked as the most serious disease in Latin America. The host?s ability to generate a cellular response against the parasite is absolutely essential in the evolution and severity of Chagas? disease. The identification of T cells responding to specific antigens of the parasite proves useful when establishing markers of the status and evolution of the disease.
Our research in this field is directed to identify cellular markers that allow links to be established between the specific responses found in different groups of Chagasic patients to the markers, severity of the disease and the post-treatment evolution of Chagas? disease. For this purpose, we have isolated and characterized several genes coding for specific T. cruzi antigens and over produced the correspondent recombinant proteins. Thus, we are interested in to establish a series of parameters, related to specific humoral and cellular responses, which could be indicative of the stage of the disease in Chagasic patients.
FUNDING AGENCIES LAST 5 YEARS
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