Heads of Team

Jamal Khalife : Contact

Phosphatases in cellular and molecular signalling in Plasmodium

It has become clear that the coordinated and reciprocal actions of kinases and phosphatases are fundamental regulation mechanisms for the development and growth of the malaria parasite. In many organisms Protein Phosphatase type 1 (PP1) is one of the major phosphatases and the most functionally and biochemically well-characterized. The PP1 catalytic (PP1c) subunit has diversified its function through the presence of regulatory proteins that form with the catalytic subunit highly specific enzymes (substrate specificity, localization/trafficking, control of the phosphatase activity of PP1c). In P. falciparum (Pf), the deadliest form of malaria, although the PP1c (PfPP1c) has been identified and despite its biological importance, very little has been reported on the regulatory subunits and on the molecular basis of the control of PfPP1c functions.

To fulfill its appropriate and precise function required during P. falciparum lifecycle, PfPP1c should be tightly and spatiotemporally controlled. On the basis of the well conserved sequence/structure of PP1c (from fungi to humans) and the high specificity of P. falciparum genome (~50-60% unknown proteins) and its distinctive cell division mechanism, it is conceivable that both conserved and specific regulators of PfPP1c are present and developed by the parasite.

Hence the general objective of our project is to characterize the regulatome of PfPP1 by mining the P. falciparum genome and by an in-depth approach using high-throughput yeast two-hybrid system. By investigating the regulators of PP1, we aim to provide fundamental insights into the regulation of PfPP1 at the molecular level. This will, in a long-term goal, permit to selectively modulate the specific signaling pathways to inhibit parasite growth.