Description of the thesis topic

Yeasts of the Candida genus are part of the natural human microbiota but can cause opportunistic infections, particularly in immunocompromised individuals, such as those in intensive care or undergoing chemotherapy. These infections can range from mild to severe, even life-threatening. Candida albicans is the most frequently encountered species, while Candida auris represents an emerging threat, known for its multidrug resistance and its association with invasive infections and high mortality rates. Additionally, Nakaseomyces glabratus is on the rise, with increasing resistance leading to more cases of invasive candidiasis. The effectiveness of current treatments is diminishing, with commonly used antifungals such as fluconazole becoming less effective, making these infections harder to treat.

The recruited person will work on the structural and functional characterization of enzymes from yeasts of the Candida genus. This project aims to express enzymes involved in the control of various cellular processes essential for the survival and adaptability of these yeasts, such as cell wall synthesis and remodeling, in a heterologous system.

The fungal cell wall is a complex and dynamic structure. It acts as an essential armor for fungal cell integrity by providing strength and shape to the growing cell, and protecting fungal cells from environmental insults. The robustness of the cell wall is critical for maintaining fungal morphology and plays a major role during infections. A biophysical, enzymatic, and structural characterization of these enzymes (including X-ray crystallography, SAXS, DLS, etc.) will be conducted.

Work Context

The Biocrystallography and Structural Biology of Therapeutic Targets team at MMSB, a multidisciplinary research unit led by CNRS and the University of Lyon, is dedicated to elucidating the molecular and cellular mechanisms behind the proliferation of pathogenic microorganisms, disease development, and drug resistance. By integrating molecular biology, biochemistry, bioinformatics, and structural biology, the team studies the structure-function-activity relationships of protein targets, providing crucial insights for the advancement of innovative therapies.
Information about the MMSB laboratory:
Address: IBCP, 7, passage du Vercors, 69007 Lyon
Website: https://mmsb.cnrs.fr
Research theme: MMSB is a multidisciplinary research unit led by CNRS and the University of Lyon. Its mission is to understand, at the molecular and cellular level, how pathogenic microorganisms multiply and cause diseases, and how pathologies develop drug resistance. MMSB is one of the main contributors to the SFR BioSciences, where it hosts the Protein Sciences Facility, which includes preparative biochemistry on bacterial and mammalian cells, structural studies (X-ray, EM), and mass spectrometry. It is located at the heart of the Lyon Biosciences Campus in the Gerland district.
Staff: Approximately 70 permanent researchers and a similar number of interns.
The position is in a sector subject to the protection of scientific and technical potential (PPST), and therefore, in accordance with regulations, your arrival must be authorized by the competent authority of the Ministry of Higher Education and Research (MESR).

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

NA

Additional Information

NA