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Filament branching during infection by a human opportunistic fungal pathogen

Project description

Mechanisms and regulation of morphological transitions in Candida infection

Fungal infections are associated with millions of deaths every year. Fungal virulence requires that the pathogens have the ability to undergo a reversible transition from yeast to filamentous form, and nutrients and other factors can alter filamentous branching during infection. Funded by the Marie Skłodowska-Curie Actions programme, the BranchOut project aims to determine the importance and regulation of branching in the human opportunistic fungal pathogen Candida albicans during infection. The researchers will use live-cell imaging in different growth conditions to understand the biophysics and spatial regulation of the branching. Application of genetic approaches at the cellular level in conjunction with optogenetics will identify the molecular mechanisms of branching regulation in fungal infection.

Objective

Fungal infections result in millions of deaths and billions of superficial infections each year. Morphological transitions are critical for fungal virulence. Filamentous hyphal branching is affected by nutrients and suggested to be altered during infection. The aim of this interdisciplinary project is to determine the importance of branching in the human opportunistic fungal pathogen Candida albicans. Specifically, how is branching controlled and regulated in time/space during infection? Towards this goal, I will investigate branching at the molecular/cellular levels, and use genetic/molecular perturbation to delineate functions and requirements of branching. Live-cell imaging will be used to determine the frequency and position of hyphal branching, as a function of infection-relevant conditions, including growth on/in different stiffness substrates, physical confinement, nutrients and gaseous environment. This will help us to characterize the biophysics of branching and to understand the spatial regulation of the process. To address how branching is
affected by host cells, this process will be followed in co-culture with reconstituted human epithelia To determine at molecular/cellular levels the critical processes and components that localize to incipient branch sites, I will use different fluorescent reporters. Targeted and unbiased, genetic/molecular approaches will be used to probe the functions and requirements of branching and selected mutants will be examined in mice. Using optogenetics, I will investigate perturbation of branching by induction of de novo branching. In summary, this interdisciplinary project, that takes advantage of cutting-edge imaging, molecular approaches and biophysics tools, will shed light on the importance and regulation of branching during fungal infections.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 196 707,84
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Hauts-de-Seine
Activity type
Research Organisations
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Total cost
€ 196 707,84
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