Post-doc

We are seeking a highly motivated and talented post-doctoral fellow to join our team, Unité de Biologie et Pathogénicité Fongiques (headed by Pr C. d’Enfert) at the Institut Pasteur, Paris. Our team focuses on the physiopathology of Candida yeasts, responsible for superficial and invasive fungal infections. The project aims to understand the function and biosynthesis of β-1,6-glucan, a cell wall polymer, and is part of a multidisciplinary consortium comprising to other teams: Sarah Wong (Immunology of Fungal Infections, Institut Pasteur) and Lionel Ballut (Institut de Biologie et de Chimie des Protéines, Lyon).

C. albicans is the major Candida yeast species accounting for about 100 million mucosal infections and ~400,000 systemic infections per year. The increase in the number of strains that are multi-resistant to antifungal agents is leading to a growing incidence of two other species, C. glabrata and C. auris. Being a complex and dynamic structure that protects and essential for survival, the fungal cell-wall (CW) plays a prominent role during infection by favouring fungal invasion into host system. Therefore, the key-steps in CW biosynthesis are potential antifungal target, as the CW disruption leads to fungal death.

The CW of Candida yeasts is a 3D layered structure, composed of mannoproteins as well as other polysaccharides (β-1,3-glucan, β-1,6-glucan and chitin). Being external, fungal CW is the first to interact with the host immune system and thereby leads to immunomodulation. However, it has been observed that C. albicans remodels its CW in response to environmental change. This dynamic change during infection affects the exposure of the CW polysaccharides, consequently the host immune response. The CW organizational specificities have been observed among Candida species. For example, the emerging multidrug resistant C. auris shows stronger host immune response due to masked β-1,3-glucan and exposed mannans in its CW.

β-1,6-glucan, another major polysaccharide of the C. albicans CW, links the internal and external components of the CW (see PMID: 39636210). Despite being a critical constituent of the CW, the biosynthesis and remodelling, dynamics in response to the external environment and immunomodulatory potential of β-1,6-glucan remain poorly studied. The project focuses on the dynamic of β-1,6-glucan exposure by immunofluorescence, biosynthesis and immune response.

Key Responsibilities:

• Conduct high-quality research on cell wall analysis of Candida species.

• Using confocal microscopy imaging, flow cytometry and biochemistry and genomic techniques.

• Obtention of cell wall mutants by gene deletion.

• Contribute to the publication of research findings in high-impact journals.

• Participate to consortium meetings and collaborate with the members of the consortium.

• Ph.D. in microbiology, fungal biology or a related field.

• Experience with imaging, fungal molecular biology and flow cytometry techniques.

• Excellent communication and teamwork skills.

• Proven track record of scientific publications.

The first objective is a comparative study of the exposure of β-1,6-glucans and β-1,3-glucans to the yeast cell surface as a function of environmental conditions and between clinical isolates. This approach will be based on confocal microscopy and cytometry using monoclonal antibodies. The second objective is to identify new genes or proteins involved in the synthesis and remodelling of β-1,6-glucans in C. albicans.