A novel fungicide target for crop protection from fungal pathogens

Fungal diseases cause devastating losses of crops and there is an urgent need for new fungicides to combat this, as resistance grows to existing treatments. Novel modes of fungicide action are especially valuable as they may bypass existing resistance mechanisms. Recent research at the University of Nottingham has revealed a promising new fungicide target; namely, fidelity of the essential process of protein synthesis. By combining agents which alter accuracy of mRNA translation by different mechanisms, a synergistic elevation of mistranslation rate and fungal inhibition is observed. This action appears specific to fungi. The synergy additionally means that agents are effective at far lower concentrations than when supplied singly. These decreased quantities offer improved cost-effectiveness and safety profile, while the use of combinations normally slows resistance development. A PhD studentship in this area is extremely timely, offering an outstanding training opportunity for a young researcher.

The overall objective of this project will be to improve understanding and development of the novel fungicide target. This will be achieved by: (i) Corroborating mode of action (MoA) of key combinations. This know-how gained by the student will inform identification and development of additional agents predicted to have the same target. (ii) Finding novel combinations with similar MoAs. The most effective existing agents will be used to find new combinations that produce synergistic growth inhibition by screening chemical libraries available in Nottingham and at Syngenta, industrial partners on this project. The project includes an industrial placement at Syngenta. The screens will use the yeast model for convenience in high-throughput format, before testing novel lead combinations for efficacy against key phytopathogens. (iii) Phytopathogen range and selectivity. The student will examine a broad range of phyopathogens including isolates resistant to existing fungicides, to characterise phylogenetic relatedness or other feature that determines sensitivity to the novel fungicides. This project will help to corroborate that fungi express mechanisms required for the synergy to work which are absent in non-target organisms. This important analysis will give added breadth to the student’s training, complementing the preceding phytopathogen-focused experiments.

There will be outstanding training opportunities to build a foundation of transferable skills. The student will also benefit from specific research training through experts at Nottingham and Syngenta in fungal molecular biology, genome sequencing, luminometry and plant infections. The student will join active research groups, benefitting from a close collaboration between academia and industry, with excellent networking opportunities.

Candidates interested in applying for this project should send a CV, cover letter and 2 references to Professor Simon Avery ([Email Address Removed]). Candidates shortlisted for interview will be contacted in due course.