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Centre d'Immunologie et des Maladies Infectieuses
UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255

Dynamique, structure et biologie moléculaire de l'invasion fongique

Dynamique, structure et biologie moléculaire de l'invasion fongique - a. Weiner

Membres de l'équipe

Programme de recherche

Fungal pathogens account for as many deaths each year as tuberculosis or malaria. The opportunistic fungal pathogen Candida albicans colonizes the skin, genital and intestinal mucosa of most healthy individuals and is part of the normal commensal flora. In susceptible hosts, C. albicans can invade the gastrointestinal mucosa and enter the bloodstream, leading to severe systemic infection.

C. albicans invasion presents a challenging arena for investigation, as it encompasses a complex set of inter-species interactions shaped over millions of years of evolution in a so called “arms race”. Events at this interface are often highly transient and involve pathogen subversion of host pathways, as well as the activation of host defense mechanisms. Understanding C. albicans invasion is a major challenge, requiring a combination of dynamic, structural and molecular approaches.

The aim of our lab is to study the mechanisms of Candida albicans invasion into epithelial layers at the single cell level using multi-dimensional fluorescent microscopy, cell biology and correlative light and electron microscopy.

Candida infection

During infection, C. albicans cells attach to host epithelial cells.  C. albicans cells then switch from a rounded yeast form to a filamented hyphal form. Hyphae can then invade and damage host cells. We study these events using three main approaches:

Dynamic microscopy

We use advanced light microscopy approaches to determine the precise dynamics of invasion at the single cell level. Experiments are performed using a fully automated microscope capable of imaging live C. albicans infections over many hours.

Cell biology

We study the mechanisms of invasion using fluorescently labeled proteins, stains, siRNA, drugs and mutant strains. We aim to establish the precise host factor recruitment hierarchy during invasion and investigate various pathogen factors regulating invasion.

Correlative light and “volume” electron microscopy

In recent years a new family of electron microscopy (EM) approaches collectively known as “volume EM” have emerged. These approaches are capable of imaging much larger cellular volume than conventional EM at nanometer resolution. 


doi.org/10.1111/cmi.12963

We study the structure of invasion using a correlative approach where the same invasion event is imaged using both light microscopy and volume EM. The two acquired data sets are then computationally combined providing quantitative three-dimensional molecular and ultrastructural information.

 

Expertise technique de l'équipe

Financement contractuel

07/11/18

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    Contact

    cimi-paris @ upmc.fr