Novel genome-wide transcriptomic approaches to challenge Candida albicans-hosts interactions
Aims of the project
This project aims to use several genomic approaches in order to discover novel cellular factors involved in the interaction of the human pathogen Candida albicans with cells of the host. The project is composed of three different complementary research partners, each of which will contribute to different aspects of the project. The first two partners (D. Sanglard, University of Lausanne and University Hospital Center, CHUV, and S. Leibundgut, ETHZ) will contribute to the understanding of fungal and host factors in the fungal-host interactions, respectively. The third partner (M. Pagni, University of Lausanne) will be associated with the genomic data analysis and development of bioinformatic tools.
The occurrence of infections with the yeast Candida albicans in patients with deficiencies in their immune system is still associated an important clinical problem with a high mortality. Antifungal therapies exist, however their efficiency is limited, which therefore necessitate the identification of novel antifungal molecules. The interactions of C. albicans with its host are complex and depend on both fungal and host -derived factors. The fungal factors that are critical for the maintenance of C. albicans within the host could constitute novel source of targets for new antifungals. Transcription factors (TF), which control the expression of gene targets and coordinate the response of C. albicans in its interaction with the host, play an important role for C. albicans persistence in the host.
Methods and saignificance
In this research proposal, in order to identify novel transcription factors important for the interaction of C. albicans with its host, we plan to use high throughput RNA sequencing (HTRS) technologies to probe the gene expression profiles from the host and the fungus interacting with each other.
Partner 1 (D. Sanglard) has identified novel C. albicans TFs required for host interactions. Mutants for these TFs display an enhanced or attenuated infectivity, respectively, when tested in a systemic mouse infection model. Here, Partner 1 aims at functionally characterizing the target genes of these TFs and their regulation during infection by using HTRS.
Partner 2 (S. LeibundGut-Landmann) will investigate the host response to C. albicans in order to identify specific immune mechanisms that are affected by the TF mutants. For this, several assays with mouse cells cells will be combined with HTRS analyses.
Partner 3 (M. Pagni) will use HTRS to probe both the fungal and host genes expression profiles with the goal to identify novel host response pathway that contribute to C. albicans control in the host.
The results obtained from this project will advance our current understanding of the intimate crosstalk between the fungus and its host and will open up new opportunities for the future development of novel therapies.