Yellow rust (YR) disease is a major threat to cereal crops and grasses worldwide, causing significant losses to the global wheat harvest each year. The long-term aim of this research is to develop new varieties of wheat with enhanced resistance to YR. To do this, it is essential to understand host specificity - the ability of the pathogen to specialize on particular grass hosts, coupled with the ability of the host to resist infection by different strains of YR. I recently pioneered a field-based 'pathogenomics' approach to enable a comprehensive evaluation of the genetic diversity of YR. This new method provides unparalleled resolution of the pathogen population that can identify gene families associated with the ability to cause disease on all the major hosts of YR in Europe, namely wheat barley, rye, triticale and cocksfoot grass. Using this approach, I previously uncovered a genetically distinct population of YR on triticale and showed that these isolates contained gene clusters that were specifically expressed in all isolates identified on triticale and had no or negligible levels of expression in all wheat YR isolates. In this ERC project, I will use the pathogenomics approach to collect an extensive dataset of YR on all its major hosts, aiming to characterise genomic regions and the genes they encode to understand the underlying regulatory mechanisms that drive host specialization and adaptation. I will then assess changes at the transcriptomic level in closely related host-specialized YR races to provide insights into how pathogens adapt to new hosts. In parallel, I will identify host targets of effectors from YR to resolve the underlying molecular processes that are targeted by the pathogen to enable successful host-specific colonization. I will then disrupt the function of these host targets using precision genome editing to determine their contribution to YR pathogenicity and reveal novel susceptibility genes that are essential for pathogen progression.

Crop yield depends in a large part on stem height and inflorescence structure. Mutations that reduce stem growth have been used widely to improve crop yields but also have undesired side effects, for example during seed formation. In spite of its importance, stem development is poorly understood. Fundamental knowledge of how genes control stem growth is required to develop more precise genetic tools to increase plant productivity by modifying plant height and shape. The ARABIDOPSIS THALIANA HOMEOBOX1 (ATH1) gene inhibits stem development but is rapidly downregulated prior to the floral transition to allow elongation of the inflorescence stem. Data from the host lab indicate that ATH1 integrates two of the key hormonal signals that control stem growth: gibberellin (GA) and brassinosteroid (BR). My objectives are to reveal the mode of action of ATH1 and use this knowledge to develop new ways of modifying plant height with fewer undesired side-effects. I will reveal how ATH1 influences GA and BR signalling, understand molecular mechanisms of ATH1 action and identify cis-regulatory mutations that result in dwarf plants due to persistent ATH1 expression after flowering. Such mutations would be particularly useful for two reasons: first, regulatory mutations have been selected repeatedly in evolution and crop improvement because they allow subtle changes in gene expression, with fewer pleiotropic effects. Second, this type of mutation would be expected to be dominant and especially useful in polyploid crops. In addition to addressing a fundamental problem with practical use, this work will give me cutting edge training in plant developmental genetics and quantitative phenotyping at cellular and macroscopic levels. At the same time, the project will benefit from my knowledge of plant hormonal signalling and extensive experience in genome editing. More broadly, the work will provide me with a valuable network on international contacts and skills for my future career.

Abiotic stress tolerance is genetically complex, displaying continuous variation because the effects of individual genes (so called Quantitative trait loci), cannot be discerned. The aim of this project is to deploy genetic and genomic tools to map and clone such genes. This is an essential prerequisite for understanding their modes of action and making them available as targets for genetic manipulation by plant breeders. The work has particular emphasis on wheat since this is the UK's most important agricultural crop. The work is focused on conditions where limited availability of nirogen and water reduces grain yield.

My research encompasses the discovery, characterisation and engineering of pathways that make drug-like molecules in actinomycete bacteria. I am particularly interested in bioactive natural products that also possess unusual structural features. We employ a "gene to product" approach, which requires a wide variety of techniques, such as the computational analysis of bacterial genomes, the genetic manipulation of gene clusters and the in vitro analysis of pathway proteins. Two major routes to peptide natural products have evolved: non-ribosomal peptide synthetases (NRPSs) and ribosomally synthesized and post-translationally modified peptides (RiPPs). We study the biosynthesis of complex metabolites produced by both types of pathway. NRPSs are massive multi-domain assembly line proteins and are responsible for the biosynthesis of the glycopeptide antibiotics. These hugely complex molecules are used as drugs of last resort to treat aggressive methicillin-resistant Staphylococcus aureus (MRSA) infections. Through a variety of collaborations, I am investigating the regulation, activity and biosynthesis of these molecules. In contrast to NRPSs, RiPPs originate from ribosomal precursor peptides. Bottromycin is a clinically promising and structurally unique RiPP, and is active towards multi-drug resistant bacteria, such as MRSA. Its structurally novelty makes it a promising lead compound in the fight against infection. Following the discovery of the bottromycin pathway in Streptomyces scabies, we are now characterising the enzymatic steps of this pathway to determine how structural complexity is introduced into this compound. Additional work on this pathway includes mutagenesis to produce novel derivatives and an analysis of the regulatory factors that control bottromycin biosynthesis. This research will inform future investigations into other novel RiPP pathways.

Wild relatives of wheat have useful charcteristics such as increased tolerance to drought, salt and cold as well as resistance to various diseases. To meet the requirements of growing wheat under climate change and poor soil conditions, it will become increasingly important to be able to exploit such characteristics by transferring the genes responsible for such traits to wheat. However this transfer into wheat by conventional breeding has previously been very difficult because of the complexity of the wheat genome. Wheat has three sets of genetic information, or genomes, which inherently should make wheat genetically unstable. Stability is conferred by a gene complex, known as Ph1, which effectively prevents recombination of genes across the different genomes. Genes in genome A can only recombine with genes from A, B with B, etc. The good news is that it makes wheat genetically stable. The bad news is it also makes it very hard to get desirable genes from wild species into modern wheat varieties. But now, following extensive research into the Ph1 mechanism, we believe that we know how to temporarily switch off the Ph1 gene complex allowing breeders to transfer in useful 'wild' genes, without upsetting the genetic stability in the field. It will greatly increase the pool of genetic material breeders can use to improve varieties.