Reducing animal usage in antifungal drug development: iRFP reporter strains and imaging fungal infection

Fungal infections remain a major cause of illness and disease globally, with their rising resistance to antifungal drugs driving a need to discover and evaluate new therapies. A major step in the pre-clinical development of new antifungal agents is testing their efficacy in mouse fungal infection models.
The aim of this project is to develop and create fungal reporter strains which express a fluorescent protein, allowing fungal infection and the effectiveness of antifungal therapies to be visualised and monitored in live animals. This builds on a previous pilot project which allowed us to develop a Candida albicans reporter strain. Although previous luminescent reporter strains have been developed by others, these have been less effective in systemic infections as most require administration of substrates into the host animal prior to imaging the infection, and there are issues with high background levels and difficulties in detecting signal from deep within the animal. Our reporter does not require administration of a substrate and emits near-infrared fluorescence, with little background and better detection of signals from within the animal.
Use a fluorescence reporter strain will allow the repeated imaging of individual animals, meaning that infection progression and responses to antifungal therapies can be analysed in individual animals, rather than sampling groups of animals at different time points. This will allow a significant reduction in the number of animals required for these tests and, from current publications, we estimate that animal numbers could be reduced by 36%. Further reductions may be possible if the variation is lower when individual animals are monitored.
The studentship is designed to evaluate the Candida albicans iRFP reporter strain in response to antifungal therapies, to develop reporter strains for two other pathogenic fungal species and evaluate those in appropriate mouse models of infection and antifungal therapy and finally to engage with industrial collaborators to evaluate novel antifungal agents. Training will be provided in molecular biology, microbiology, experimental biology and in vivo biology, as well as courses for career and personal development. The project is planned to be achievable within 36 months, whilst providing scope for the student to further develop the project.