Fungal pathogens are expert manipulators of their plant hosts, which they achieve through secreting effector proteins which disable host defences. However, sometimes effectors are recognised by plant immune receptors to trigger rapid defence responses. Effectors are therefore both an asset for the pathogen, and a weakness, as they can potentially activate host immunity.
We want to take cutting-edge advances in AI-based protein biology to design synthetic proteins that can help plants fend off fungal pathogens. These synthetic proteins will either (1) directly bind to fungal effectors to stop them working, or (2) be incorporated into immune receptors to confer a new recognition ability to the host plant. We recently identified a number of immune-suppressing effectors from the wheat pathogen Zymoseptoria tritici which we will use as targets in this project.
The student will learn computational protein design pipelines (eg. RFdiffusion, BindCraft) and produce both effectors and synthetic proteins in heterologous expression systems (bacterial, yeast, insect). Pairwise interactions will be tested in vitro by isothermal titration calorimetry (ITC) or microscale thermophoresis (MST) in collaboration with the lab of Prof. Andy Lovering. Protein interactions in plants will be tested using Agrobacterium-mediated transient expression in Nicotiana benthamiana. We anticipate that the highest affinity interactions will be both detectable by ITC/MST and modify effector phenotypes in plants. This project will be an important proof-of-concept that AI-designed synthetic proteins can interact with pathogen effectors and either suppress their activity, or allow us to build new immune receptors to bolster plant defence.
For informal enquiries, please contact Dr Graeme Kettles at g.j.kettles@bham.ac.uk.
For more details please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/ or https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership
Funding notes:
This is a PhD studentship with the Midlands Integrated Biosciences Training Partnership, funded by BBSRC and in partnership with the University of Warwick, University of Birmingham, Aston University, Harper Adams University, Coventry University, and the University of Leicester.
