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SUMMARY OF RESEARCH
Identification of antigens and immunostimultatory molecules candidates for inmunotherapy against trypanosomatid pathogens
Parasites of the Trypanosomatidae family are the etiological agent of leishmaniosis and American tripanosomiasis (Chagas? Disease) characterized by presenting unspecific clinical symptoms together with an alteration of the host immune system. The parasites are transmitted by insect vectors, producing high morbidity and mortality rates. It has been estimated that 300 million persons live in endemic areas and that there are 500.000 new cases each year. Nowadays iin development countries there has been a high increase in the rate of infection due probably to the existence of additional transmission ways, such as blood transfusions (T. cruzi). As it occurs for Leishmania infantum, there is a higher rate of canine infections and an association with immunosupression states.
Given that existing chemotherapy is toxic and not very specific, vaccines, despite the difficulties involved in their developing, are probably the most effective way of responding to the world-wide important problem presented by these infectious pathologies. Although the protective antiparasitic response mechanisms of the host are not fully understood, it is clear, for both diseases, that effective protection requires induction of a multiple immune response incorporating serialized cellular activation and antibody production with a balance towards Th1 and induction of parasite´s antigen-specific CTLs. Undoubtedly, it requires immunization with suitable antigenic protein/s associated to carrier molecules, stimulators/modulators of the immune response. The genetic vaccines or DNA vaccines, as well as recombinant proteins, may be an excellent way of inducing this type of multiple response and of generating effective protection.
The scientific objective of our laboratory is focused on identifying and studying at molecular and immunological level specific proteins from Leishmania and Trypanosoma cruzi which are antigenic molecules and candidates for vaccines, as well as their encoding genes. Likewise, we have special interest in the characterization of biological molecules with immunostimulatory capability. The final aim of the laboratory is directed to analyze the capacity of the chimeric recombinant proteins or DNA vectors to limit the pathological consequences of leishmaniosis and trypanosomiasis and to induce protection against parasite´s infection
Study at molecular level of the transposition and integration mechanism of L1Tc mobile element from T. cruzi. Analysis of its functionality
The genome of a large number of prokaryotic and eukaryotic organisms contains a surprisingly high proportion of repeated long and short interspersed nucleotide elements (LINE and SINE) DNA sequences with the potential capacity to transpose in the host genome. These mobile elements have been considered for decades as selfish elements. However, at present these sequences have been taken as important elements to generate variations in genome structure and expression associated to species evolution. Although the biological properties of these sequences (regulation, replication and interaction with their host organisms) are not well understood, the available data indicate that they represent challenging and fascinating biological elements playing crucial functional roles. In this context the resolution of these functions and mechanisms will be essential to know how the repeated elements dialogue to achieve the concrete modeling of the genetic information and consequently to fully understand the biology of the host organisms.
The genome of the parasite pathogen Trypanosoma cruzi has a large proportion of repeated and dispersed DNA sequences which share common characteristics with SINE sequences from higher eukaryotes, and a LINE type element known as L1Tc encoding for the enzymes required for its retrotransposition. These retrotransposon sequences have been linked to the high plasticity observed in the T. cruzi genome and furthermore, seem to be involved in the chromosomal organization and control of the expression of specific genes, crucial for the pathogenicity and survival of the parasite.
The objectives of our laboratory are focused on the characterization of the molecular and functional characteristics of the different polypeptides encoded by the LINE-L1Tc element from T. cruzi as well as its putative regulatory sequences. Likewise, we are interested in determining at molecular level, the retrotransposition and integration mechanisms of this mobile element and in the identification of the effect that de novo retrotransposition events have on the genome of the aforementioned parasite pathogen.
FUNDING AGENCIES LAST 5 YEARS
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