|Trypanosome Cell Biology - CNRS URA 2581|
|HEAD||Dr. BASTIN Philippe (DR2 INSERM) / firstname.lastname@example.org|
|MEMBERS||BLISNICK Thierry (experimental officer) BUISSON Johanna (PhD student) COZANET Anne (secretary) HUET Diego (PhD student) Dr. JULKOWSKA Daria (post-doc) Dr. MARANDE William (post-doc, collaboration with the Muséum of Natural History) Dr. ROTUREAU Brice (post-doc) SUBOTA Ines (PhD student) Dr. VINCENSINI Laetitia (post-doc)
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. During their life cycle, these parasites have to adapt to changing environments (mammalian bloodstream, insect gut and salivary glands) and undergo profound morphological and biochemical modifications. 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) flagellum formation and function and (2) the dynamics of trypanosome infections in vivo.
Flagellum formation and functions. The flagellum is a cylindrical organelle made of microtubules and composed of more than 200 proteins. We previously demonstrated that the flagellum is critical for the trypanosome cell cycle and that it is constructed by a specific process called intraflagellar transport (IFT). We have set up optimal conditions to visualise and quantify the movement of fluorescent proteins in the flagellum. FRAP analysis revealed the dynamics of exchange of IFT proteins between the basal body and the flagellum compartment. We have identified 4 different sub-units of the retrograde motors and discovered their organisation and their role in the entry of various IFT proteins in the flagellum. We recently discovered a couple of small G proteins that could act as regulators of IFT. These data have been extended to the related parasite Leishmaniawhere drastic changes of flagellum length take place during the life cycle.
Dynamics of trypanosome infections. In addition to its functions in motility and morphogenesis, the flagellum has been proposed to act as a sensory organelle. We have now purified intact flagella and analysed the content of their membrane and matrix fraction, revealing exciting candidates that are currently under investigation. Using our recently set up experimental infections of tsetse flies in the laboratory, we have characterised spectacular changes in the flagellum and in the trypanosome cytoskeleton during the course of differentiation and migration. We identified some putative RNA binding proteins and revealed their importance during the parasite cycle, especially at various stages of trypanosome development in tsetse flies.
Trypanosome as a model for genetic diseases. Several genetic diseases are linked to defects in cilia and flagella function. Trypanosomes are an excellent model to study these diseases as mammalian, insect or nematode ciliated cells do not propagatein vitro and are poorly amenable to transfection. We are working with three clinical groups to understand the role of cilia and flagella in several ciliopathies. For example, the role of a leucine-rich repeat protein involved in primary ciliary diskynesia has been analysed successfully in trypanosomes.
Keywords: Trypanosome, flagellum, cytoskeleton, tsetse fly, primary ciliary diskynesia, Bardet-Biedl Syndrome, nephronophtisis
1.>Demonchy R, Blisnick T, Deprez C, Toutirais G, Loussert C, Marande W, Grellier P, Bastin P, Kohl L. (2009)Kinesin 9 family members perform separate functions in the trypanosome flagellum.J Cell Biol. 187:615-22.PMID: 19948486.
2.Duquesnoy P, Escudier E, Vincensini L, Freshour J, Bridoux AM, Coste A, Deschildre A, de Blic J, Legendre M, Montantin G, Tenreiro H, Vojtek AM, Loussert C, Clément A, Escalier D, Bastin P, Mitchell DR, Amselem S. (2009) Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia. Am J Hum Genet. 85:890-6. PMID: 19944405.
3.ADHIAMBO C., BLISNICK T., DELANNOY E., TOUTIRAIS G., BASTIN P. (2009) A novel function for the atypical small G protein Rab-like 5 in flagellum assembly of trypanosomes. J. Cell Sci., 122, 834-41. PMID: 19240117.
4.ABSALON S., BLISNICK T., BONHIVERS, M., KOHL L., CAYET N., TOUTIRAIS G., BUISSON J., ROBINSON D.R., BASTIN P. (2008) Flagellum elongation is required for correct structure, orientation and function of the flagellar pocket in Trypanosoma brucei. J. Cell Sci., 121, 704-3716. Front cover. PMID: 18940910.
5.ABSALON S., BLISNICK T., KOHL L., TOUTIRAIS G., DORE G., JULKOSWSKA D., TAVENET, A., BASTIN P. (2008) Intraflagellar Transport and Functional Analysis of Genes Required for Flagellum Formation in Trypanosomes. Mol. Biol. Cell19, 929-944. Cited on F1000. PMID: 18094047.
Activity Reports 2009 - Institut Pasteur
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