Trypanosome Cell Biology - CNRS URA 2581  


  HEADDr. BASTIN Philippe / pbastin@pasteur.fr
  MEMBERSABSALON Sabrina (PhD student) / Dr. ADHIAMBO Christine (post-doc) / Dr. BRANCHE Carole (post-doc)
BLISNICK Thierry (experimental officer) / BUISSON Johanna (M2 student) / Dr. JULKOWSKA Daria (post-doc)
Dr. Brice ROTUREAU (post-doc) / Ines SUBOTA (PhD student) / Dr. VINCENSINI Laetitia (post-doc, collaboration Trousseau hospital)
Wendy HOUSSIN (secretary)


  Annual Report

Trypanosomes are flagellated parasites responsible for various tropical diseases, including sleeping sickness in Central Africa caused by Trypanosoma brucei and transmitted by the bite of the tsetse fly. Trypanosomes also represent exciting model organisms as they exhibit unique cellular features and are amenable to modern reverse genetics technology. Our group is interested in two topics: (1) biology and applications of RNA interference (RNAi) and (2) flagellum formation and function.

RNA interference. RNAi is a sequence-specific RNA destruction process mediated by short or long double-stranded RNA that was discovered in 1998 by C. Mello and A. Fire (Nobel winners 2006). We previously identified a gene essential for RNAi and showed that this process participates in chromosome segregation during mitosis and in the control of the abundance of transcripts derived from transposable elements and related pseudogenes (mobile elements make up 5 % of the trypanosome genome and > 40 % of the human genome). We are now analysing stages downstream of the RNAi cleavage and investigating the feasibility of delivery of siRNA to trypanosomes.

Flagellum formation and functions. The flagellum is a cylindrical organelle made of microtubules and composed of more than 200 proteins. We demonstrated that the flagellum is critical for the trypanosome cell cycle and have characterised its role in cell motility. We showed that it is constructed by a specific process called intraflagellar transport and identified a dozen genes involved in this mechanism. Recently, we have visualised the movement of fluorescent proteins in the flagellum and are currently studying the mode of regulation of this activity. Flagellum aspect is modified during the infection of the tsetse fly insect vector, although little is known about this crucial process for the parasite cycle. We recently set up experimental infections of tsetse flies in the laboratory and are now investigating the behaviour of the trypanosome flagellum in this context.

Trypanosome as a model for genetic diseases. Several genetic diseases are linked to defects in cilia and flagella function. However, mammalian, insect or nematode ciliated cells do not propagate in vitro and are poorly amenable to transfection. Our data reveal that trypanosomes are an excellent model to study these genetic diseases. We are working with two clinical groups to understand the role of cilia and flagella in the Bardet-Biedl Syndrome and in Primary Ciliary Diskynesia.

Keywords: Trypanosome, ARN interférence, flagelle, cytosquelette, maladies génétiques

Bct.jpg

A. Wild-type trypanosome (bar, 1 µm). B. Trypanosomes stained for DNA (blue) expressing a fluorescent flagellar protein (green). C. Mutants with short or no flagella.



  Publications

1. ABSALON S., BLISNICK T., KOHL L., TOUTIRAIS G., DORE G., JULKOSWSKA D., TAVENET, A., BASTIN P. (2007), Intraflagellar Transport and Functional Analysis of Genes Required for Flagellum Formation in Trypanosomes., Mol Biol Cell. 2007 Dec 19; [Epub ahead of print] PMID: 18094047 (selected by the Faculty of 1000).

2. ABSALON S., KOHL L., BRANCHE C., BLISNICK T., TOUTIRAIS G., RUSCONI F., COSSON J., BONHIVERS M., ROBINSON D.R., BASTIN P. (2007), Basal body positioning is controlled by flagellum formation in Trypanosoma brucei.PLoSOne 2 : e437. PMID: 17487282

3. BRANCHE C., KOHL L., TOUTIRAIS G., BUISSON J., COSSON J., BASTIN P. (2006), Conserved and specific functions of axoneme components in trypanosome motility. J. Cell Sci. 119, 4343-4355. PMID: 16882690

4. Durand-Dubief M., Bastin P. (2003), TbAGO1, an Argonaute protein required for RNA interference is involved in mitosis and chromosome segregation in Trypanosoma brucei.BMC Biol. 1, 2 http://www.biomedcentral.com/1741-7007/1/2(more than 14,000 downloads) PMID: 17822785

5. KOHL L., ROBINSON D.R., BASTIN P. (2003) Novel roles for the flagellum in cell morphogenesis and cytokinesis of trypanosomes.EMBO J. 22, 5336-5346 (with front cover). Commented in Hurtley S.M. (2003) A dead-end short cut. Science 302, 535; Jones S. (2003) Trypanosome flagellum-motility and more. Nature Rev. Microbiol. 1, 172-173. PMID: 14532107





Activity Reports 2007 - Institut Pasteur
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