Engineering synthetic disease resistance genes to tackle plant pathogens

Plant pathogens hamper agricultural productivity and pose a clear and present danger to our food systems. Plant diseases alone account for 10-80% of global crop losses, enough to feed several billion people. Breeding broad-spectrum disease resistance is regarded as sustainable way of managing crop diseases. Plants rely on immune receptors encoded by the resistance (R) genes that can sense and eliminate pathogens. Due to their high potency in plant protection, R genes have been bred into virtually every crop from various germplasms. The problem is that R gene mediated resistance is often defeated by the rapid evolution of pathogen populations. Therefore, timely identification of new R genes that are effective against emerging pathogen races is a major challenge. Here we aim to generate synthetic immune receptors (R genes) with new resistance specificities to keep up with rapidly evolving pathogens. R genes carry leucine-reach repeat (LRR) domains comprised of individual repeat modules implicated in ligand sensing.

We will exploit the modular nature of these proteins and focus on engineering the LRR domains to generate new ligand binding interfaces. We will generate a synthetic LRR library by using a novel recombination-based approach that efficiently allows the shuffling of LRRs that are present in existing R genes. We will screen the synthetic LRR library with ligands encoded by the pathogens to identify new LRR-ligand partners by using a well-established proteomics approach. The LRRs capable of binding pathogen ligands will be incorporated into various available R gene scaffolds ("synthetic R genes") to identify the most suitable synthetic R gene-Ligand pairs that can mount appropriate immune responses. At the completion of this work, we expect to design synthetic disease resistance genes that confer new specificities or broad-spectrum resistance against agronomically important plant pathogens.

The 2016 UK Roadmap Bio-design for the Bio-economy highlighted the substantial impact that synthetic biology can bring to the UK and global economies by developing: frontier science and technology; establishing a healthy innovation pipeline; a highly skilled workforce and an environment in which innovative science and businesses can thrive. Synthetic biology promises to transform the UK Bio-economy landscape, bringing bio-sustainable and affordable manufacturing routes to all industrial sectors and will ensure society can tackle many contemporary global Grand Challenges including: Sustainable Manufacturing, Environmental Sustainability Energy, Global Healthcare, and Urban Development. Whilst synthetic biology is burgeoning in the UK, we now need to build on the investments made and take a further lead in training next generation scientists to ensure sustained growth of a capable workforce to underpin the science base development and growth in an advanced UK bio-economy.
This training provided by this CDT will give students from diverse backgrounds a unique synthesis of computational, biomolecular and cellular engineering skills, a peer-to-peer and industrial network, and unique entrepreneurial insight. In so doing, it will address key EPSRC priority areas and Bioeconomy strategic priorities including: Next-generation therapeutics; Engineered biomaterials; Renewable alternatives for fuels, chemicals and other small molecules; Reliable, predictable, and scalable bioprocesses; Sustainable future; Lifelong health & wellbeing.
Advances created by our BioDesign Engineering approach will address major societal challenges by delivering new routes for chemical/pharma/materials manufacture through to sustainable energy, whilst providing clean growth and reductions in energy use, greenhouse gas emissions and carbon footprints. Increased industry awareness of bio-options with better civic understanding will drive end-user demand to create market pull for products. The CDT benefits from unrivalled existing academic-industry frameworks at the host institutions, which will provide direct links to industrial partners and a direct pathway to early economic and industrial impact.

This CDT will develop 80-100 next-generation scientists and technologists (via the funded cohort and wider integration of aligned students at the three institutions) as adept scientists and engineers, instilled with technical leadership, who as broadly trained individuals will fill key skills gaps and could be expected to impact internationally through leadership roles in the medium term. Importantly the CDT addresses key skill-gaps identified with industry, which are urgently required to create and support high value jobs that will enable the UK to compete in global markets. Commercialisation and entrepreneurship training will equip the next generation of visionaries and leaders needed to accelerate and support the creation of new innovative companies to exploit these new technologies and opportunities.

The UK government identified Synthetic Biology as one of the "Eight Great Technologies" that could be a key enabler to economic and societal development. This CDT will be at the forefront of research that will accelerate the clean growth agenda and the development of a resilient circular bioeconomy, and will align with key EPSRC prosperity outcomes including a productive, healthy and resilient nation. To foster wider societal impact, the CDT will expect all students to contribute to public outreach and engagement activities including: open days, schools visits, and science festival events: students will participate in an outreach programme, with special focus on widening participation.

This CDT will contribute to the development of industrial strategy through the Synthetic Biology Leadership Council (SBLC), Industrial Biotechnology Leadership Forum (IBLF), and wider Networks in Industrial Biotechnology and Bioenergy and Professional Institutes.