Biology, Genetics and Pathology in pathogenic eucaryotes

 Patrick BASTIEN

 MIVEGEC - UMR 5290/U 224 IRD

 39 avenue Charles Flahaut, 34395 Montpellier Cedex 5

Phone: +33 4 67 33 23 50

Email: patrick.bastien@umontpellier.fr

Website  

The laboratory of Patrick Bastien has been engaged in studies on the molecular biology of the protozoan parasites Leishmania and Trypanosoma for more than 25 years. The previous genomics works of this group were pioneer in the set-up of the genome sequencing project for these parasites. They now explore the molecular features of their cell biology, and particularly mitosis, with a specific interest in the reproduction/distribution of the genetic material, e.g. chromosome replication and segregation. They characterised a number of protein families (kinesins, katanins...) typically involved in structures linked to these processes (kinetochores, centrosome, spindle) but with surprises as their characterization may lead to unsuspected functions. Thus, one of the 6 microtubule-depolymerizing kinesins present in these organisms (vs. two in man) was found to be involved in flagellum length maintenance - allowing defining a novel model for the length regulation of this organelle. They also discovered how irregular chromosome distributions can lead to 'mosaic aneuploidy', a unique genetic feature, allowing the parasite to adapt to its environment through drastic genomic changes leading to a fluctuant aneuploidy within the cell population. Finally, they have interest in an 'extra' proteasome of the prokaryotic type, present in the single mitochondrion of these organisms, which they validated as a potential drug target; the characterization of specific molecular pathways being seen as one 'upstream' approach for potential drugs against pathogens.

Keywords: Mitosis, cell cycle, genomics, Typanosoma, Leishmania

Main publications

• Garcia-Silva Mr, Sollelis L, Macpherson C, Stanojcic S, Kuk N, Crobu L, Bringaud F, Bastien P, Pagès M, Scherf A, Sterkers Y. Identification of the centromeres of Leishmania major: revealing the hidden pieces. EMBO Rep. 2017; 18(11):1968-1977.
• Stanojcic S, Sollelis L, Kuk N, Crobu L, Balard Y, Schwob E, Bastien P, Pages M, Sterkers Y. Single-molecule analysis of DNA replication reveals novel features in the divergent eukaryotes Leishmania and Trypanosoma brucei versus mammalian cells. Sci.  Reports 2016; 6:23142-… (doi 10.1038/srep23142)
• Morelle C.*, Sterkers Y.*, Crobu L., Mbang-Benet D.E., Kuk N., Portales P., Bastien P., Pagès M., Lachaud L. The nucleoporin Mlp2 is involved in chromosomal distribution during mitosis in Trypanosomatids. Nucleic Acids Res. 2015; 43(8):4013-27.
• Casanova M., De Monbrison F., Van Dijk J., Janke C., Pagès M., Bastien P. Characterisation of polyglutamylases in trypanosomatids. Int. J. Parasitol. 2015, 45(1): 131-132. S
• Sterkers Y, Crobu L, Lachaud L, Pagès M, Bastien P. Parasexuality and mosaic aneuploidy in Leishmania: alternative genetics. Trends Parasitol. 2014, 30(9):429-35.
• Sterkers Y.*, Lachaud L.*, Crobu L., Bastien P., Pagès M. FISH analysis reveals aneuploidy and continual generation of chromosomal mosaicism in Leishmania major. Cell Microbiol., 2011, 3 : 274-83.
• Marín C, Alberge B, Dollet M, Pagès M, Bastien P. First complete chromosomal organization of a protozoan plant parasite (Phytomonas spp.). Genomics, 2008, 91:88-93.
• Casanova M., Portalès P., Blaineau C., Crobu L., Bastien P., Pagès M., Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in Trypanosomatids. Cell Death & Differentiation 2008, 15:1910-20.
• Sterkers Y, Scheidig C, da Rocha M, Lepolard C, Gysin J, Scherf A. Members of the low-molecular-mass rhoptry protein complex of Plasmodium falciparum bind to the surface of normal erythrocytes. J Inf Dis, 2007;196:617-21.
• Blaineau C., Tessier M., Dubessay P., Tasse L., Crobu L., Pagès M., Bastien P. A novel microtubule-depolymerising kinesin involved in length control of a eukaryotic flagellum. Current Biology 2007, 17:778-82.
• Dubessay P., Blaineau C., Bastien P., Tasse L., Van Dijk J., Crobu C., Pagès M. Cell cycle-dependent expression regulation by the proteasome pathway and characterization of the nuclear targeting signal of a Leishmania major Kin-13 kinesin. Mol Microbiol, 2006, 59:1162–1174.
• Dubessay P., Ravel C., Bastien P., Crobu L., Dedet J.P., Pagès M., Blaineau C. The switch region on Leishmania major chromosome 1 is not required for mitotic stability or gene expression, but appears to be essential. Nucleic Acids Res., 2002, 30: 3692-97.