PROJECT: Fungal pathogens infect more than a billion people worldwide, with invasive fungal infections causing more annual death than tuberculosis or malaria. Cryptococcus is among the three major human fungal pathogens and has been recently identified in a list of pathogen of critical priority by the WHO. Extracellular vesicles (EVs) are lipidic nanosized particles that deliver complex molecular cargo between cells and organisms. It has been shown that fungal EVs could be implicated in cell-to-cell communication but could be also involved in antifungal resistance and biofilm formation. However, the cellular mechanisms underlying the secretion of fungal EVs across the CW have not been elucidated yet.
The fungal cell wall is an essential structure with great plasticity essential for cellular integrity and viability and mediates interactions with the host. Moreover, in Cryptococcus, the CW is surrounded by a capsule playing a role in virulence. It has been shown by Cryo-EM analysis that EVs are observed next to areas of damaged CW indicating that EVs could be released after CW injury and potentially that hydrolases associated with vesicles could play fundamental roles in cell wall passage. Accordingly, the FunWallEVs project will investigate the mechanisms of EV secretion across the CW in C. neoformans.
Our objectives aim to study the EV production of several crucial CW and capsule mutants and decipher the CW structure and composition of the cells during EV secretion. We will also decipher enzymatic activities associated to EVs and investigate their involvement in CW passage. CANDIDATE PROFIL: We are looking for an experienced, motivated, independent and dynamic candidate. Candidate should have solid experience in molecular biology, as well as microbiology and mycology. The successful applicants will have a high degree of flexibility in research directions and approaches. The position is available from January 2025 for a period of 3 years.
APPLICATIONS: Please send applications including CV with names and contact information of 2 referees, a complete list of publications list and a detailed statement of research interests directly to imouyna@pasteur.fr.
STARTING DATE: The position is available in January 2025 in the RNA Biology and Fungal pathogens Unit under the supervision of Dr. Isabelle Mouyna but duration of the settlement of all administrative paperwork is expected to be two months. Salary will be commensurate to previous experience and in line with Institut Pasteur.
LABORATORY PUBLICATIONS RELATED TO THE TOPIC:
Rizzo J, Wong SSW, Gazi AD, Moyrand F, Chaze T, Commere P-H… Janbon G. Cryptococcus extracellular vesicles properties and their use as vaccine platforms. J Extracell Vesicles. 2021;10: PMID: 34377375
Rizzo J, Trottier A, Moyrand F, Coppée JY, Maufrais C, Zimbres ACG, Dang TTV, Alanio A, Desnos-Ollivier M, Mouyna I, Péhau-Arnaude G… Janbon G (2023) Coregulation of extracellular vesicle production and fluconazole susceptibility in Cryptococcus neoformans. mBio. (2023) 13: e0087023. PMID: 37310732
