Control of gene expression and genetlc plasticity in Leishmania

Abstract

The present proposal aims at the use of comparative genomics and reverse genetics in the study of gene expression regulation and genetic plasticity in the protozoan parasite Leishmania. The proposed studies and approaches are in alignment with, and expand the projects that are being conducted in our laboratories (FAPESP Proc. 99/12403-3). We consider the investigation of occurrence and mode of action of ncRNAs in Leishmania a topic of high relevance. The results gathered so far encourages further investigation and introduce new concepts on gene expression regulation in this organism The attempts to demonstrate a RNAi machinery in L. major were unsuccessful, which might be due to molecular differences that are inherent to any given organism. Therefore, our proposal is to investigate the mode of action of a particular ncRNA, named ODD3, whose expression exerts a clear effect on the expression of other genes and results in drastic phenotypic changes. The interaction among RNA molecules will be investigated in order to understand the role of their sequence and the secondary structure they form in the observed effect. The possible interaction between transcripts and proteins mediating the effect of ODD3 transcript excess will also be investigated. In another sub-project on gene expression regulation we will investigate the ribosomal protein L19, which is differentially expressed during the L. major life cycle... (AU)