Translational control mechanisms in Candida albicans: Exploring the link between RNA helicases and pathogenicity determinants

• Applicant: Professor Dr. Joachim Morschhäuser
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 515862017

The yeast Candida albicans is part of the normal microbial flora in most healthy people, but it can also become a pathogen and cause superficial as well as life-threatening invasive infections when host defences are compromised. The ability of C. albicans to colonize and infect virtually all body locations relies on its successful adaptation to the changing environmental conditions encountered in different host niches, which includes appropriate adjustments in gene expression. Research over the past decades has provided detailed insights into transcriptional control mechanisms in C. albicans. Many signaling pathways and transcription factors that regulate morphogenesis, metabolic adaptations, and the response to the presence of antifungal drugs have been uncovered, and the corresponding changes in transcript abundance have been determined on a genome-wide scale. However, genes are also regulated at the posttranscriptional level, and surprisingly little is known about translational control of gene expression in C. albicans. In this collaborative Indo-German research project we use state-of-the art techniques and our complementary expertises to elucidate the translational regulation of gene expression in C. albicans on a genome-wide level and the mechanisms of this control. We will determine which of the genes that enable metabolic adaptations to nutrient availability, the transition from the budding yeast to the invasive hyphal morphology, and the development of antifungal drug resistance are translationally regulated. We will reveal which features of mRNAs are required for translational control and investigate the role of the DEAD-box RNA helicases eIF4A (eukaryotic initiation factor 4A) and Ded1, which have not been characterized so far in C. albicans. We will study the phenotypes of mutants lacking these helicases and the effect of their inactivation on global translational control as well as on the translational efficiency of specific genes with key functions in hyphal morphogenesis, metabolic adaptation, and drug resistance. The results of our studies will expand our understanding of how one of the medically most important fungi adapts to life in its human host and can become pathogenic, and they will also reveal conservation and divergence of translational control mechanisms in eukaryotes.

• DFG Programme: Research Grants
• International Connection: India
• International Co-Applicant: Dr. Neelam Sen