Research objectives and content
The interconversion between the tachyzoite and the bradyzoite stages of T. gondii is an important event in the pathogenesis of the disease, particulary in AIDS patients. In an immunocompetent host, the acute phase caused by the multiplication of the proliferative stage (tachyzoite) is followed by the chronic phase caracterized by the encystment of the parasite in a dormant form (bradyzoite). The conversion of these latent forms into tachyzoites is the main cause of the toxoplasmic reactivation in immunocompromized individuals. The mechanisms that promote the tachyzoite bradyzoite interconversion in T. gondii are yet poorly known. We propose to investigate the regulation of the stage - specific gene expression during stage conversion in order to understand the determinism of the process. In a first step, we plan to characterize the promoter of a bradyzoite - specific gene. The core promotor element of tachyzoite - specific gene has recently been identified. The transcriptional and the post - transriptional level at which the regulation of stage - specific gene expression occurs could be studied using the pro-cedures inducing the bradyzoite differentiation in vitro and the transfection strategy recently developped in the parasite. In a second step, we will intend to identify transcriptional factors interacting with the core promoter elements of the stage - specific genes by using genetic approaches . Sequences controlling the stage specificity of the gene expression have not been identified. The proposal work should contirbute to the characterization of such signals and then allow a better understanding of the determinism of the stage conversion.
Training content (objective, benefit and expected impact)
I expect to extend my knowledges about technics and concepts related to the study of gene expression regulation and improve my experience in the field of the molecular biology technologies . So, at my come back in France, my new acquired expertises should help me to go on the work on the study of the determinism of stage conversion in T. gondii.
Links with industry / industrial relevance (22)