Abstract
The protozoan Leishmania, etiological agent of diseases of indisputable medical importance, has peculiar forms of genome organization and expression. The aim of this proposal is to investigate key elements of genetic variability and post-transcriptional regulation of gene expression. In specific lines of investigation, we will study genome variation in response to DNA replication stress; the expression and mechanisms of action of non-coding RNAs and the role of post-translational modifications in development and host-parasite interaction. These studies will use state-of-the-art approaches in cellular and molecular biology, such as: genomic editing by CRISPR-Cas9; global analysis and/or prospecting strategies such as ChIP-seq and BioID; in-vivo RNA-RNA or RNA-protein interaction studies; and multi-color FISH assays of single molecules. The proposal has a strong component of strengthening of existing and new collaborations with international laboratories, reinforcing the vocation of our laboratories for international network collaboration. Thus, this proposal aims to contribute remarkable advances in the field of RNA expression regulation and the understanding of genomic variability in trypanosomatids. (AU)
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