Étude du déterminisme du pouvoir pathogène de la levure pathogène Candida albicans par des approches de génomique et de biologie des systèmes

 

Adnane Sellam

Centre de recherche du CHU de Québec

Centre hospitalier universitaire de Québec

Domaine : génétique humaine

Programme chercheurs-boursiers - Junior 1

Concours 2015-2016

Candida albicans is an opportunistic pathogen responsible for various non-life-threatening infections, such as oral thrush and vaginitis. This pathogen is also a major cause of mortality in bloodstream infections, especially in immunosuppressed individuals. The arsenal of clinically active antifungal compounds is limited because of the eukaryotic nature of this yeast, which makes it similar to its human host. In addition, many cases of clinical resistance to all anti-Candida drugs have been reported. Currently, the pipeline of pharmaceutical industries for new drugs targeting C. albicans infections is completely dry. Thus, discovery of new drugs is of utmost urgency to fight C. albicans infections. The purpose of this proposal is to gain a deep knowledge on mechanisms that control the virulence of C. albicans. This will lead to identification of proteins or biological processes that are required for the establishment of the infection. Screens of chemical libraries will identify bioactive molecules that inhibit these proteins and consequently limit the infections.
The main objective of this proposal is deciphering regulatory circuits that control the adaptation to hypoxia and the coordination of growth and division. These biological processes are both intimately linked to C. albicans virulence. In parallel, several chemical libraries will be screened to find small molecules inhibiting filamentation and biofilm formation, which are key manifestations of C. albicans pathogenicity. We will also use pioneering computational approaches to predict antifungal peptides targeting and compromising virulence factors.

In addition to uncovering the molecular mechanisms controlling C. albicans virulence, this research program will improve our understanding of how a eukaryotic organism such as C. albicans respond to hypoxia and control the coordination of growth and division. This knowledge can be translated to other eukaryotes such as the human to understand complex diseases linked to the inappropriate regulation of these processes.