Tropical Parasite Molecular Biology Group

Madrid

Our research group undertakes fundamentally basic research into two aspects of the biology of the parasitic Leishmania protozoa, namely: regulation of gene expresión and approach to vaccine development.

The parasitic protozoa of the genus Leishmania are aetiological agents of diseases with widespread geographical distribution known as leishmaniases. These diseases are endemic in 88 countries across Africa, Asia, Europe, and Central and South America. It is estimated that 12-14 million persons are currently affected by these parasitoses, with 1.5-2 million new cases annually (WHO, http://www.who.int/leishmaniasis/en/).Leishmania has a digenetic life cycle, alternating between flagellated promastigotes forms, which multiply in phlebotomi, and obligate intracellular aflagellated amastigotes that multiply within macrophages of the vertebrate host. In Spain and other countries around the Mediterranean Basin, the endemic species is Leishmania infantum, the cause of the severest form of the disease, visceral leishmaniasis (kala-azar). This species is also the cause of an important veterinary disease, canine visceral leishmaniasis. Currently, there is no effective prophylactic method against any type of leishmaniasis, and chemotherapeutic treatments do not have the desirable efficacy.

As a eukaryote, Leishmania is atypical: all protein-coding genes, as in other trypanosomatides, are structured in long transcriptional units that generate polycystronic RNAs, which are finally processed into monocystronic mRNAs by "trans-splicing" and polyadenylation. Our group is interested in the study of gene expression mechanisms in L. infantum. Specifically, we are studying HSP83/90 and HSP70 gene regulation. In this digenetic parasite, exposed to changes in temperature, the heat shock response is associated with morphological differentiation. We have shown that heat shock response regulation occurs exclusively at a postrancriptional level and involves sequences located on the 3'UTR regions of the mRNAs, which modulate mRNA stability and translation efficiency.

Furthermore, our group has been engaged in studying a number of antigens of the parasite, with regard to their ability to develop protective immunity against the infection. In particular, noteworthy progress has been made on the use of DNA vaccines that express genes for the nucleosome histones of L. infantum.

Severo Ochoa Molecular Biology Centre, Autonomous University of Madrid

 
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