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Intravital imaging of infection

Intravital imaging of infection

By In Aiv Internship On June 6, 2019


Internship title: Intravital imaging of infection

LABORATORY
Name: Pathogenesis of Vascular Infections” Unit
Affiliation: Institut Pasteur, “Cell Biology and Infection” Department
Address: 28 rue du Docteur Roux 75015 Paris
E-mail: guillaume.dumenil@pasteur.fr

LAB Director
Name: Guillaume Duménil
Phone number: 0144389383
E-mail: guillaume.dumenil@pasteur.fr

SUPERVISOR
Name: Guillaume Duménil
Phone number: 0144389383
E-mail: guillaume.dumenil@pasteur.fr

Subject Keywords: bacteria, infection, intravital imaging, innate immunity, vascular biology
Tools and methodologies: Live-intravital microscopy, immunofluorescence, animal, surgery, image treatment
Summary of lab’s interests: A number of infectious agents, including emerging pathogens and agents responsible for nosocomial infections, reach the blood during infection. Colonization of the bloodstream induces different types of severe pathological consequences such as septicemia and meningitis. Despite the availability of antibiotics these infections resulting in sequels and high death rates remain a major concern in intensive care units and emergency rooms. A better basic understanding of the mechanisms of disease is a necessary step to the identification of innovative treatments. Our model system is Neisseria meningitidis (or meningococcus), a Gram-negative bacterium that recapitulates these different pathological effects. We study these infections with a global and multidisciplinary approach combining microbiology with cell biology, vascular biology, chemistry and physics to study the pathogenesis of N. meningitidis infection.
Project summary: Infectious diseases leading to colonization of the blood by the infectious agent are a major burden to society and lead to a wide array of devastating clinical manifestations including septic shock, hemorrhagic syndromes and infection of the brain (meningitis). The main goal of the proposed project is to decipher the pathophysiological processes underlying these infections focusing on the innate immune response to intravascular colonization by the bacterium Neisseria meningitidis. A xenograft-based humanized mouse model of infection by this bacterium will enable in vivo characterization of the innate immune response (Bonazzi et al. and Melican et al.). The experimental approach will be based in particular on dedicated in-house spinning disk confocal microscopy-based intravital imaging allowing fast, high resolution multicolor imaging.

Bonazzi D, Lo Schiavo V, Machata S, Djafer-Cherif I, Nivoit P, Manriquez V, Tanimoto H, Husson J, Henry N, Chaté H, Voituriez R, Duménil G (2018) Intermittent pili-mediated forces fluidize Neisseria meningitidisaggregates promoting vascular colonization. Cell 174, 1–13, June 28, 2018.

Melican K, Michea Veloso P, Martin T, Bruneval P, Dumenil G (2013) Adhesion of Neisseria meningitidis to dermal vessels leads to local vascular damage and purpura in a humanized mouse model. PLoS Pathog 9: e1003139.

Interdisciplinary aspect of the project: Physical processes including mechanics and soft matter physics are at the heart of the disease process. The project integrates a multidisciplinary approach by combining classical cell biology techniques, live microscopy, microfabrication and image analysis. The student will take advantage of the lab wide expertise to learn how to manipulate pathogenic bacteria, define optimal and robust experimental conditions and write scripts (Matlab, Fiji etc.) for data analysis. All these quantitative tools will be of great help also in other pathogenic contexts, opening the possibility to collaborate with other laboratories within the Institute or abroad.