Biology of Apicomplexan Parasites: factors regulating growth, differentiation and virulence


Team leader:

Jamal KHALIFE
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Activities

The apicomplexan parasites Plasmodium and Toxoplasma gondii, causative agents of malaria and toxoplasmosis respectively, continue to present a public health menace and to weigh heavily on the socio-economic development in certain regions. Once inside host cells, these parasites set up a highly coordinated gene expression programs to promote their growth/differentiation. Concomitantly, diverse biological processes including post translational modifications (in particular reversible protein phosphorylations) of expressed proteins and their trafficking are initiated to keep their functions in fine-tuning with the progress of parasites life cycles. Our current research is focusing on three main research topics.  In the first topic, we investigate the regulatory complexes that govern the expression of virulence factors in Toxoplasma gondii. We aim at understanding the role of the ApiAP2 family of transcription factors and epigenetic regulation of gene expression. We are particularly interested in discovering how transcription factors act in complex to regulate the gene expression program essential for proliferation and differentiation of this parasite. In the second topic, we examine reversible phosphorylation processes with particular emphasis on issues related to phosphatases and their regulation. Currently, our studies are mainly dedicated to explore the function and regulation of Plasmodium/Toxoplasma protein phosphatase type 1 or PP1, an essential ser/thr phosphatase for the (sur)vival of any eukaryotic cell. The third research topic aims to elucidate the molecular mechanisms that regulate the secretion of essential virulent parasitic factors contained in dense granules, a trafficking pathway which remained fully unexplored. By using reverse genetics, advance proteomics approaches, super-resolution microscopy and live imaging, we aim to identify the key regulatory mechanisms of this pathway in T. gondii and search for conserved mechanisms in P. falciparum. 

The final goal of our basic research is to provide a better understanding of the molecular events contributing to the life cycles progression of these parasites and, ultimately, to control malaria and toxoplasmosis by translating the new fundamental knowledge into the development of therapeutic strategies.


 

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