Definition of processing and regulation of double-stranded RNA in the human fungal pathogen Aspergillus fumigatus

The human fungal pathogen Aspergillus fumigatus was listed among the critical priority group of the WHO fungal priority pathogens list of 2022. This classification highlights the importance to investigate molecular mechanisms of the fungus and develop novel antifungal drug strategies. The RNA interference (RNAi) machinery is a conserved system in many different organisms. During the canonical process, double-stranded RNA (dsRNA) is cleaved into small RNAs, which leads to post-transcriptional silencing. While the RNAi pathway is ubiquitous in all domains of life, it can be lost in individual genera. The RNAi system in A. fumigatus consists of three main components: dicer, argonauts and RISC complex; which makes it a good model organism to study dsRNA regulation in pathogenic fungi. In A. fumigatus RNAi contributes to regulation of stress response and virulence. Interestingly, previous work has shown that high amounts of dsRNA can be toxic to the fungus. The resulting research question focuses on how RNAi is involved in housekeeping tasks and how the overexpression of dsRNA impacts the fungal fitness. Investigating dsRNA binding proteins could reveal interesting aspects of regulation and interaction. Additionally, analysis of the proteins involved in the RNAi pathway could give insight into shared mechanisms and unique aspects of the studied RNAi system. Investigating the molecular mechanisms and housekeeping functions of additional RNase III enzymes could reveal non-canonical dsRNA processing pathways. These findings will not only help to understand functions and features of the RNAi pathway, but lay the fundamentals to investigate more complex systems. Additionally, research of the RNAi pathway will likely lead to the discovery of potential drug targets and help address the increasing number of Aspergillus infections.

PhD start: 11/03/2025