PhD PROPOSAL FOR THE PASTEUR-PARIS UNIVERSITY INTERNATIONAL PROGRAM

 

Deadline for full application: December 15th, 2013

Interviews: March, 2014

Start of the Ph.D.: October 1st, 2014

 

 

Department: Parasitology and Medical Mycology

Title of the PhD project: Flagellum sensing during the early steps of mammalian host infection by African trypanosomes

Name of the lab: Trypanosome cell biology unit

Head of the lab: Philippe Bastin

PhD advisor: Brice Rotureau

Email address: rotureau@pasteur.fr

Web site address of the lab: http://www.pasteur.fr/research/trypa

Doctoral school affiliation and University: Complexité du vivant ED515

 

Presentation of the laboratory and its research topics:

Our lab is studying the role and functioning of the trypanosome flagellum, with perspectives in the field of both parasitology and genetic diseases. Indeed, trypanosomes are significant parasites of man and cattle in central Africa and there are currently no efficient vaccines against them. Moreover, trypanosomes are also an excellent model to study human genetic diseases due to defects in cilia and flagella. Our lab is a Pasteur full research unit of about 12 members affiliated to the Department of Parasitology and Mycology and the Department of Cell Biology and Infection. We also belong to a larger CNRS unit (URA2581, headed by Artur Scherf).

 

Description of the project:

Human African Trypanosomiasis or sleeping sickness is a neglected tropical disease caused by the flagellated protist Trypanosoma brucei. Nagana is a similar disease in cattle due to closely related trypanosome species. The injection of these extra-cellular parasites by the bite of the tsetse fly induces a local inflammatory response. Trypanosomes then apparently transit via the lymphatic system before invading the bloodstream where they proliferate and cause the typical symptoms of the disease. However, very little is known about the early steps of infection, especially the mechanisms of trypanosome differentiation, proliferation and passage to the bloodstream. The first aim of this project is to characterize these early steps of T. brucei development upon natural transmission of a fluorescent strain by a tsetse fly bite using state-of-the-art intravital imaging technologies. Particular attention will be paid to parasite motility, proliferation, morphogenetic modifications and interactions with host cells. The second goal is to establish the importance of the trypanosome flagellum that has been proposed to be a key virulence factor. Functional investigations with conditional knockout parasites will be performed to discover the role of flagellum sensory functions in detection of the environment and activation of the appropriate differentiation programs by targeting two types of proteins, a membrane protein concentrated at the distal tip called FLAM8 and a couple of aquaporin channels of the flagellar pocket. Overall, these studies will result in the first integrated view of the early steps of trypanosome infection and will be crucial to improve early diagnosis and treatment of this disease that is always fatal in the absence of treatment.

 

References:

Rotureau B et al. Development. 2012 May; 139(10):1842-50.

Subota I et al. Mol Biol Cell. 2011 Nov; 22(22):4205-19.

Rotureau B et al. Cell Microbiol. 2011 May; 13(5):705-16.

 

Keywords: Trypanosome, Tsetse, Host, Infection, Flagellum, Sensing

 

Expected profile of the candidate (optional): Skills in parasitology / microscopy / entomology

 

Contact: brice.rotureau@pasteur.fr

Mis à jour le 16/09/2013