Mechanisms and fitness penalties of fungicide resistance (BROWNJ21DTP)

Evolution of resistance to drugs and pesticides is a serious challenge to control of infectious diseases in both agriculture and medicine. It is also one of the clearest demonstrations of natural selection in action. Knowledge about the mechanisms and evolution of resistance will inform the design of new anti-microbial compounds and new strategies for disease control.

In this project, the student will investigate the evolution of resistance to morpholine fungicides as a model for fitness costs of resistance. The morpholines are a small but important group of fungicides used in agriculture and medicine, which target two proteins in the sterol biosynthesis pathway, ERG24 and ERG2. Although some crop pathogens have become partially resistance to morpholines, there has been no known outbreak of complete resistance in commercial farming. This is a striking contrast to experience with other fungicides, suggesting that resistance to morpholines involves a significant fitness penalty. Morpholine chemistry may thus have potential for development of new fungicides with durable activity for controlling diseases of crops, people and other animals.

The student will test this hypothesis by studying the effect of mutations in ERG24 and ERG2 on responses to morpholines. This will first involve identifying sequence variation associated with morpholine resistance in crop pathogens. The ERG genes will be mutagenised in yeast as a model organism, using a range of CRISPR/Cas9 protocols for site-directed mutagenesis and saturation mutation. The effects of selected mutations on the biology and fitness of the fungus will then be investigated, including responses to fungicides, the structure of the ERG proteins, membrane sterol composition, and fungal growth and development. The project will give a student outstanding training and research experience in molecular genetics, molecular evolution and plant pathology.

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Thursday 7th January, Friday 8th January and Monday 11th January 2021.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.