PhD Studentship: Engineering the Yeast Cytochrome bc1 Complex for the Development of New Antifungal Inhibitors

Primary Supervisor - Dr David Swainsbury 

Cytochrome (cyt) bc₁ complexes are central to electron transport chains in many species of bacteria and in mitochondria. The essentiality of this complex makes it a promising target for the development of new compounds that target human and plant pathogens. However, producing pure proteins from these pathogens in a laboratory environment is challenging because these organisms are often not genetically tractable, cannot be cultured on large scales, and can pose significant risks to researchers or the environment. Fungal pathogens of crop plants pose a major threat to global food security. Fungal diseases cause between 10% and 23% loss in global yields every year, which directly impacts availability and cost of food. Whilst there are many fungicides available to combat this issue, resistance is quick to develop meaning that new antifungal agents are urgently needed. 

In collaboration with Syngenta, we are working on engineering the yeast cytochrome bc₁ complex to generate a new model system for the rapid and safe development of new antifungal agents. We combine a suite of modern methods, including computational tools for protein engineering, structure determination by cryogenic electron microscopy, mechanistic studies by enzymology and electron paramagnetic resonance spectroscopy, and genetic engineering by CRISPR. The engineered organisms will provide an ideal platform to aid discovery of new inhibitors of this key enzyme and understand the mechanisms by which pathogens become resistant to fungicides. 

Applications are encouraged from students interested in exploring the molecular mechanisms of enzymes using structural and computational methods. This project combines the skillsets of several laboratories spanning the Norwich Research Park and Syngenta to provide training in a suite of techniques, including molecular biology, computational protein engineering, enzymology, electron paramagnetic resonance spectroscopy and cryogenic electron microscopy. 

For informal enquiries please contact Dr David Swainsbury (d.swainsbury@uea.ac.uk). 

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2025 entry. The programme 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 CASE students undertake a three to 18-month placement with the non-academic partner during their study. The placement offers 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. Shortlisted applicants will be interviewed on 28, 29 or 30 January 2025.  

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. 

Funding Details

Additional Funding Information

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2024/5 stipend rate: £19,237), and a Research Training Support Grant of £5,000pa for each year of the studentship. 

Closing Date: 25 November 2024 (at 11.59 pm) 

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