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Dernière mise à jour mardi 18 juin 2013, par
Institut Pluridisciplinaire Hubert Curien - IPHC
Département Sciences Analytiques - DSA
Centre National de la Recherche Scientifique - CNRS
UMR 7178 CNRS/Université De Strasbourg - UDS
23 rue du loess, 67037 Strasbourg cedex 2, France
Contact : Gilles Schnell
Titre de la thèse : Analyses protéomique et peptidomique des molécules impliquées dans la borréliose de Lyme
Période : 2011-2014
Encadrant(s) : Laurence Sabatier
Tick borne diseases constitute a major veterinary and human health problem. Lyme borreliosis, due to the bacterial complex Borrelia burgdorferi sensu lato, is the most important vector borne disease in the Northern hemisphere. After inoculation through an Ixodes tick bite, a cutaneous inflammation can appear at the site of inoculation, the erythema migrans. Then, different clinical manifestations can develop : cutaneous, neurological or articular according to the Borrelia-infecting pathotype. These differences in clinical manifestations could be linked in part to specific virulent factors facilitating pathogen dissemination.
First, we will select three human isolates of B. burgdorferi sl, one for each major pathogenic species (B. burgdorferi ss, B. garinii and B. afzelii) responsible of neuroborreliosis, the most frequent disseminating manifestation in Europe. Then, the selected isolates will be cultured on solid phase to identify clones with different virulent profiles in a murine model. Their dissemination to target organs in mouse, the cutaneous inflammatory profile and the proteins relevant in the early transmission will be studied. Thus, for each Borrelia species, the native strain and a virulent clone will be characterized by proteomic approaches to get the protein profile. By differential analysis, we expect to identify proteins potentially involved in bacterial virulence and dissemination.
The cutaneous interface is a key organ by its immunity in arthropod borne diseases and there pathogens multiply intensively. Then, we will use a targeted SRM mass spectrometry approach to look ex vivo for specific Borrelia proteins expressed in skin samples of infected mice and essential in the early transmission. We will look for the molecules of virulence detected by electrophoresis and nanoLC-MS/MS and common to the three main Borrelia species. Skin samples of mice experimentally infected with the different Borrelia strains will be first tested, then human samples.
These two approaches could allow the identification of vaccine-candidates for Lyme borreliosis and could also potentially be used for in vitro early diagnosis.
Keywords : Borrelia, innate immunity, antimicrobial peptides, cutaneous inflammation, pathotypes