Pasche Valérian

Master Student


Research Project

I am interested in the co-evolutionary arms race of host-pathogen interactions. An important component of this arms race is host’s ability to recognize the pathogen. Host identification of the pathogen mobilizes the host immune system and the pathogen is therefore under strong selection to avoid detection and evade the host immune response. At the molecular level, host-pathogen recognition interactions involve antigenic pathogen surface proteins and specific host recognition receptors such the antibodies of the vertebrate host immune system.
For my Master project, I am using a Borrelia afzelii pathogen – rodent host system as a model to study the molecular adaptations of a pathogen towards its vertebrate host. B. afzelii is a spirochete bacteria that belongs to the B. burgorferi s.l. genospecies complex. This complex of spirochete pathogens is responsible for Lyme borreliosis, the most common tick-borne disease in the northern hemisphere. The Borrelia pathogen is vectored among vertebrate hosts by Ixodes ticks during the blood meal. In Europe, B. afzelii is one of the most important causes of Lyme disease.
I am particularly interested in the outer-surface protein (OspC), which is an antigenic protein expressed by all B. burgorferi s.l. pathogens. This protein is involved in the early infection of the vertebrate host, where it induces a strong antibody response. The OspC protein is highly variable within a Borrelia population and immunization studies on B. burgdorferi sensu stricto in the United States have shown that the antiserum is specific for a particular OspC variant. Genetic analyses of tissue biopsies have shown that only certain OspC strains are pathogenic for humans but these studies are often limited by sample size. The specificity of the anti-OspC IgG immune response has led some authors to speculate that we could use serological methods determine the identity of the infecting OspC strain in human Lyme disease patients. To date, most research on the OspC protein and the vertebrate immune response has been done on B. burgdorferi s.s. in the United States. By contrast, there is very little information on the specificity and cross-reactivity of OspC proteins in B. afzelii.
The purpose of my project is to develop recombinant OspC proteins (rOspC) and to determine whether we can use these proteins to identity the infecting strain in human Lyme disease patients. We will use antiserum from experimentally infected mice to test whether antiserum against a particular B. afzelii OspC strain is specific for the corresponding rOspC protein or cross-reactive with other rOspC variants. If these experimental infections validate the approach, we will use our rOspC proteins to determine which B. afzelii OspC strains are most commonly found in human Lyme disease patients.