RESEARCH THEMES

Our research is dedicated to membrane biogenesis and lipid metabolism that are major and essential for the differentiation and development of Apicomplexa parasites Plasmodium and Toxoplasma in their host. More recently our interest also extended to the analysis of phosphoinositides and their function in Plasmodium biology. The lab has thus developed an international reputation in malaria biochemistry and cell biology
Our programs are geared towards the functional characterization of molecular and cellular events that lead to membrane biogenesis during the development of Plasmodium parasites within host cells. The objectives are to characterize processes and to identify original features in these biological processes in comparison with mammalian cells. We have performed the functional analysis of the malarial lipid metabolism and phospholipid signaling using genetic and chemical manipulations. In addition we decipher the transcriptome and the metabolome linked to this metabolism to reveal the underlying regulatory networks in Plasmodium.
As a consequence of our fundamental studies on lipid functions in Plasmodium, we have established new concepts for the development of new pharmacological approaches for antiparasitic drugs (discovery, development and mechanism of action). We design compounds that disturb the acquisition machinery and thus prevent parasite multiplication in the host. We have proposed a clinical candidate named Albitiazolium. This drug belongs to an exciting new class of antimalarials and is developed by Sanofi, currently in phase 2 clinical trials.
We now wish to capitalise on our diverse and complementary strengths to elucidate the regulation of the Plasmodium lipid metabolism network and to characterize additional antimalarial targets. The goal is to build a robust set of experimental data which will be used to feed the computational biology platform. Mathematic modeling based on quantitative data will allow building comprehensive networking of metabolic pathways, to understand nodes of regulation and homeostasis along the cell cycle or in response to parasite environment (nutrients or pharmacological effectors) (Ovidiu Radulescu). Ultimately, this will reveal the physiological state of the parasite cell and will identify metabolic reactions of vital importance.
  Our programmes are performed by a consortium of academic laboratories through a multidisciplinary and complementary partnership, involving experts in parasitology, molecular biology, biochemistry, system biology, medicinal chemistry, pharmacology. Our team is part of many European partnerships (e.g. the Network of Excellence EviMalar) and has coordinated a multisite European Marie Curie network for training of PhD students. Additionally, the current programmes benefit from industry links for the development and registration of antimalarial drugs.

SELECTED PUBLICATIONS

• Le Roch KG, JR Johnson, etc… EA Winzeler, H Vial,  A systematic approach to understand the mechanism of action of the bisthiazolium compound T4 on the human malarial parasite, Plasmodium falciparum. BMC  Genomics, 2008, 9, 513
• Calas M., Ancelin ML., Piquet, Escale R., Ouattara M., and Vial H., Potent antimalarial activity of 2-aminopyridinium salts, amidines and guanidines. J. Med Chem., 2007, 50, 6307-15
• Vial H., Wein S, Farenc C, Bressolle F, Kocken C, Thomas A., Calas M. Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl. Acad. Sci. USA, 2004, 101, 15458- 15463
• Biagini GA, Pasini E, Hughes R, De Koning HP, Vial H, O'Neill P, Ward S, Bray P, Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs, Blood, 2004, 104, 3372-3377 [IF: 9.3]
• Baunaure, F., Eldin, P., Cathiard AM, Vial H. Characterization and proteolytic maturation of a non-mitochondrial type-I phosphatidylserine decarboxylase in Plasmodium falciparum. Molecular Microbiology, 2004, 51, 33–46
• Wein S, M Maynadier, Y Bordat, J Perez, S Maheswari, P. Bette-Bobillo, C Tran Van Ba, D Penarette-Vargas, L Fraisse, R Cerdan, H Vial; Transport and pharmacodynamics of albitazolium, a candidate antimalarial drug. British Journal Pharmacology, 2012, 166, 2263-2276
• Vial H., Wein S, Farenc C, Bressolle F, Kocken C, Thomas A., Calas M. Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl. Acad. Sci. USA, 2004, 101, 15458- 15463
• Wengelnik K., Vidal V., Ancelin ML,  Cathiard AM,  Morgat JL, Kocken C., Calas M., Herrera, S. Thomas, A. and Vial, H. A class of potent antimalarials and their specific accumulation in infected erythrocytes, Science, 2002, 295,  1311-1314.