Cyclic peptide diagnostics for Septoria infection in Wheat

Plant pathogens are a large global problem for sustainable crop production leading to losses in yield and increased expenditure for control. The fungus Zymoseptoria tritici causes Septoria tritici leaf blotch (STB) disease in wheat (Triticum aestivum) costing €1B/year in fungicidal treatment in Europe alone, and leading to up to 40% loss in crop yield if untreated.

Z. tritici invades leaves through the stomata before undergoing a biotrophic, asymptomatic phase of growth for around 9 days before switching to vigorous necrotic growth, feeding from the plant itself causing extensive damage to the leaf tissue (blotches) and leading to fungal sporulation, allowing spores to transfer to neighbouring plants via rain splash. Rapid detection of Z. Tritici infection during the biotrophic phase would allow for targeted application of fungicides leading to reduced fungicidal usage and more sustainable agriculture and food production.

Cyclic peptides are emerging as a versatile class of molecules with high affinities and specificities comparable to antibodies but without requirements for precise folded structure and less batch-wise variability. To date, cyclic peptides have not seen application as diagnostic probes for pathogens in an agricultural setting.

Cyclic peptides can be rapidly identified through the high-throughput selection technique, mRNA-display to identify peptides of interest from very large starting libraries or trillions of molecules. Diversity can be enhanced by incorporation of unnatural amino acids through codon reprogramming.

Selected proteins from Z. tritici will be used as targets to identify cyclic peptide binders through mRNA-display. Hit sequences will be identified through next-generation sequencing and important binding residues identified bioinformatically with candidate peptides then chemically synthesised for use in biophysical experiments to determine target engagement (biolayer interferometry). Promising sequences will be taken on into further experiments using Z. tritici infected plants and ultimately real-world trials to detect infected crops.

Through this project you will obtain experience in a diverse array of molecular biology techniques including protein expression and purification, production and purification of RNA and in vitro selection as well as peptide synthesis and bioinformatics (as desired). You will also have the opportunity to isolate and culture Z. tritici, infect plants in a controlled environment and learn plant pathology techniques.

The studentship should be commenced before the end of 2022.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·      a CV (including contact details of at least two academic (or other relevant) referees);

·       a covering letter – clearly stating your first choice project, and optionally 2^nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·      copies of your relevant undergraduate degree transcripts and certificates;

·      a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]. The closing date for applications is Friday 8th July 2022 at 12noon (UK time).