Antibiotics are used extensively to fight bacterial infections and have saved millions of lives. However, the bacteria are becoming resistant to antibiotics and some antibiotics have stopped working. We refer to this as antimicrobial resistance - AMR. We don't just use antibiotics for people; similar amounts are given to farm animals. More than 900 million farm animals are reared every year in the UK and antibiotic treatments are vital for their welfare, for farms as businesses, and for us to enjoy affordable food. However, farms may be contributing to the development of AMR. The aim of this project is to improve our understanding of how farm practice, especially the way in which manure is handled, could lead to AMR in animal and human pathogens. This understanding will help farmers and vets find new ways to reduce AMR, without harming their animals or their businesses. For research purposes, Nottingham University maintains a typical high performance dairy farm - its 200 cows produce a lot of milk and a lot of manure. The waste is stored in a 3 million litre slurry tank, any excess goes into a 7 million litre lagoon. This slurry is applied to fields as organic fertilizer. Cow manure contains many harmless bacteria but some, e.g. E. coli O157, can cause severe infection in people. When cows get sick they are treated with antibiotics. Udder infections are treated by injection of antibiotics into the udder. Since this milk contains antibiotics, it cannot be sold but is discarded into the slurry. Foot infections are treated with an antibacterial footbath, which is also emptied into the slurry tank. As a result, slurry tanks contain a mixture of bacteria, antibiotics and other antimicrobials that are stored for many months. The bacteria that survive in the presence of antibiotics are more likely to have antibiotic resistance. This resistance is encoded in their genes so passed to the next generation. Worse still, the genes can be passed on to other bacteria in the slurry. Before we wrote this proposal, we investigated our own farm's slurry tank to see if this might be happening. We tested 160 E. coli strains from the slurry; most carried antibiotic resistance. We also found antibiotics in the tank - including some that bacteria were resistant to. Our mathematical modellers showed that reducing spread of resistance genes in the tank might be more effective in preventing resistance than cutting the use of antibiotics. Conversations with the farm vets revealed that they knew about AMR and had changed some of their antibiotic prescriptions. But these analyses leave us with more questions than answers. In this project, we want to find out if current farming methods are contributing to the development of harmful antibiotic-resistant bacteria in slurry, bacteria that may then be encountered by humans and animals. To do this, we need to integrate scientific and cultural approaches: - What bacteria are in the slurry? How many are harmful? What resistance genes do they carry? How do these genes spread? - How long do antibiotics remain in the tank? Do they degrade? - What happens to the bacteria and antibiotics after they are spread on fields? - How do farmers, vets and scientists interpret evidence about AMR? What are their hidden assumptions? Can we improve collaborative decision making on AMR risk management? - Can we reduce resistance by avoiding mixing together bacteria and antimicrobials in slurry? - Can we predict the risk of emergence of and exposure to resistant pathogens? Can we predict which interventions are likely to be most effective to reduce AMR, taking into account both human and scientific factors? Through this research, we will learn what can realistically be done to reduce this risk; not just on this farm, but UK wide. We will work with farmers, vets and policy makers to ensure that our results will make a difference to reducing the risk of harmful AMR bacteria arising in agriculture.

This project makes a path-breaking contribution to the agenda for tackling antimicrobial resistance (AMR) by focusing scoping research and significant networking events on a link that has so far been missing from academic and policy debate - the pivotal role of corporate food retailers. The aim of the project is to address the responsibility of retailers in tackling the AMR challenge in the context of their chicken and pork supply chains, and to investigate this evolving role and how it might be shaped in the future, in the UK and at a global scale. Against a backdrop of decades of intensive farming of animals involving the use of antibiotics, it is becoming clearer that while antimicrobials are a necessary tool to maintain health and welfare on the farm, the key issue is their inappropriate and disproportionate use in animals thereby reducing availability for humans. There is food industry-wide concern that this is leading to growing resistance amongst certain bacteria such as Salmonella, Campylobacter and E-coli, placing pressure on the sector to develop and implement standards for more responsible use. Supermarket chains are a key set of actors strategically positioned to address the global challenge of reducing antibiotic use in food supply chains and raising consumer awareness as part of tackling AMR. The project will address the role of retailers in navigating the AMR challenge through their overseas as well as their national store networks, and through supply chains that flow through spaces of the global South as well as the North. Specifically, the project addresses this role by proposing scoping research and dissemination events in the UK, where policy leadership is acknowledged and where corporate retail power is well-established. Driving the momentum of the project's policy engagement will be the support of the UK government's Food Standards Agency (FSA) as a Project Partner facilitating both a pre-project scoping workshop and a dissemination workshop at the end of the research. This reflects close alignment between the project's objectives and the emerging priorities of the FSA. The objectives of the project are: (i) to map and model the current AMR challenge involving corporate food retailers through their chicken and pork supply chains; (ii) to evaluate current and evolving corporate retail strategies and standards in the UK for reducing antibiotic use in chicken and pork supply chains; (iii) to consider the role of consumer engagement in raising standards for responsible use of antibiotics in farming; and (iv) to facilitate increased dialogue between corporate food retailers and wider institutional policy and scientific networks in the UK, in order to shape future strategy for tackling AMR. These objectives will be met through four project phases conducted over eighteen months and involving both quantitative and qualitative methods that include: the mapping and modelling with trade data of the AMR problem facing UK corporate food retailers in their supply chains; interviews with retailers' food technologists and food standards policy-makers in the UK; and interviews with a sample of UK meat producers. A project website, a stakeholder report and an end-of-project workshop in London will complement academic publications, in order to communicate the findings of the scoping research to non-academic beneficiaries and to shape evolving strategy regarding corporate food retailers' roles and responsibilities in tackling AMR.

Our vision is to maximise the food potential of UK pasture by using targeted chemical processing and novel biotechnology to convert grass into nutritious edible fractions for healthier and more affordable alternative foods, making UK agriculture more resilient and sustainable. Our proposal aims to use novel chemical processing methods to extract the central edible fractions from grass (protein, digestible carbohydrates, vitamins, lipids, fibre) before culturing the yeast Metschnikowia pulcherrima on the cellulosic fraction to produce mycoprotein and a lipid suitable as a palm oil substitute. These ingredients will then be combined in a range of alternative meat and dairy products, displacing environmentally damaging imported ingredients currently used. Further processing of the waste products from the process will produce nutrient rich fertilizers and help create a model for future circular farming economies. When optimised this process would only need 10 to 15kg of fresh grass (20% dry matter content) to produce 1kg of edible food ingredients, of which approximately 25% would be lipid and 35% protein. Whilst not entirely comparable on a nutritional basis this represents a ten-fold increase in productivity compared to cattle raised for meat, or twice the productivity of dairy cows. By converting grass into edible food components, a number of advantages are realised including: - UK produced substitutes for palm oil, soya protein, and other imported food ingredients. This has environmental benefits in the UK and abroad. It will provide UK produced healthy nutritional substitutes for ingredients grown on former rainforest sites, whilst significantly reducing food miles; - Produce UK food substitutes for over two billion pounds worth of annual food imports, with the opportunity to export significant quantities of surplus produce; - Improved UK resilience to climate change as grass is more resilient to flooding and other extreme weather conditions than most other crops; - As the process is feedstock agnostic, it should work equally well with wildflower rich pasture grass. This potentially enables the reintroduction of grasslands with greater biodiversity without having an impact on the grasses usability, an environmentally beneficial by-product of the process; - Providing a commercially viable non-livestock based market for forage production that would also allow arable land that is prone to flooding to profitably return to meadow grass production; - The profitable inclusion of grass in arable rotations to help combat blackgrass and other pesticide resistant weeds; - At present, in some areas it is uneconomic to build and maintain livestock fencing, resulting in grassland in these regions having little commercial agricultural value. These grasslands will now become commercially viable, and contribute to UK food production; - Limited risk in scaling up as there is no need to invest in new farm machinery, existing forage equipment and storage facilities will suffice and the bio-processing technology is mature and already used for many other industrial applications; - Opportunities for investment in a new UK food industry; - With the production of more digestible fractions, this project would produce more sustainable, UK sourced, feed for monogastric livestock; - Initial research suggests that sufficient unutilised grass is available for the P2P process, therefore, this system should have little or no impact on grass supplies for dairy and livestock farming.

Fungal infections are a growing problem, now killing more people than tuberculosis or malaria globally. Unfortunately fungi are also becoming resistant to the main anti fungal drugs we use to treat them. We have show that this is due to mass use of antifungals in agriculture. These are needed because fungi are the main pathogens that destroy crops. Furthermore global warming is increasing the threat of fungi across plant, animal and human health. To combat this, new types of antifungal therapies are coming into medical use, however we are already seeing equivalent antifungals being used in agriculture, known as "dual-use". We urgently need a holistic framework to ensure that we don't lose the efficacy of anti fungal drugs, both as medicines and as fungicides, whilst ensuring that we can continue to ensure that our food supplies are protected. In order to address the issue of antifungal resistance we have developed a Fungal One Health and Antimicrobial Resistance Network. One health refers to approaches that seek to balance and optimise the health of people, animals and ecosystems. The key challenges we face our to be able to understand the specific reasons why emergence of anti fungal resistance occurs within a one health context, to develop early warning systems that allow us to know when resistance in occurring or spreading, to identify the key hot-spots in the environment where anti fungal resistance is occurring, and have better understanding of where antifungals are being used most across one health. This will allow us to identify appropriate countermeasures that allow us to deliver judicious stewardship of antifungals so they can be used appropriately to enable food security and animal and human health, whilst ensuring that the risk of anti fungal resistance is minimised. In order to address these challenges and deliver appropriate countermeasures we have brought together a diverse range of scientists from across the relevant disciplines, as well as key stakeholders from relevant government departments, healthcare, agrochemical and pharmaceutical industries and end users such as farmers and patients. They will contribute to 4 working groups that focus on 1: the underlying causes of dual use anti fungal resistance, 2: surveillance of anti fungal resistance, 3: understanding the role of agricultural waste streams and water as hotspots for antifungal resistance, and 4: developing countermeasures such as anti fungal stewardship and other interventions to mitigate the risk of antifungal resistance. Our key aims will be to advance our knowledge of the underlying drivers of dual use antifungal resistance, how this occurs within the ecosystem, to develop surveillance systems and antifungal stewardship toolkits. We will develop policy documents and white papers, undertake outreach with end users, the public, governmental bodies and NGOs. The Network will train the next generation of multidisciplinary researchers in this area and develop pragmatic research proposals to enable us to fight the spread of anti-fungal resistance.

We propose the creation of an Engineering Biology Hub for Microbial Foods. The aim of the Hub is to harness the joint potential of two important scientific fields - engineering biology and microbial foods - in order to transform our existing food production system into one that is better for the environment, more resilient to climatic or political shocks, and that gives consumers healthier and tastier products. Background: Current food systems are unsustainable. Traditional farming and agriculture contribute significantly to climate change, and this is exacerbated by the alarming levels of food waste. Damage to the planet is mirrored by impacts on human health: a significant portion of the global population suffers malnutrition, while diseases linked to ultra-processed and high-calorie diets continue to rise. The way we produce and consume food has to change, and to change quickly if we are to have any chance of meeting targets for clean growth. Microbial foods - produced by microorganisms like yeast and fungi - offer a way to make this urgently needed transformation. Microbial foods are produced using different types of fermentation, with this process employed to produce large quantities of protein and other nutrients (biomass fermentation), to modulate and process plant and animal-derived products (traditional fermentation) or to produce new food ingredients (precision fermentation). Microbes grow rapidly, don't need large amounts of land or water to grow, and can use food by-products ('food waste') as feedstocks. In addition, microbial foods are less affected by adverse weather and can be produced locally - reducing transport costs, carbon footprint, and our dependence on food imports. Engineering biology applies engineering principles to biology, enabling scientists to build and manufacture novel biological systems and products. Tools from engineering biology have recently been applied to optimise microbial food production, and microbes can now be manipulated to be more productive, tastier and more nutritious. Applying engineering biology to microbial foods has the potential to radically change the way food is produced, and this creates an important and timely opportunity to address some of the most critical health and sustainability challenges of our time. The Hub: The first of its kind in the world, the new Hub will build on the UK's world-leading expertise and facilities in engineering biology and microbial foods. It will bring together academics, industrial partners, food organisations and consumers in a wide-ranging and ambitious programme of work that creates a clear route from scientific research to new food products on the shelf. At the heart of the Hub's activity will be eleven research projects, each addressing a separate challenge that needs to be overcome if large-scale production of diverse microbial food products is to be achieved. Project will use cutting-edge engineering biology methods, and will benefit from the Hub's additional focus on education, regulation and commercialisation, to ensure research outputs are translated into meaningful benefits. Overall, our objectives are : - To advance research into how engineering biology can be used to produce microbial foods - To develop new capabilities for developing microbial foods using engineering biology - To open new routes for this research to benefit human health and environmental sustainability Meeting these objectives will establish the Hub as an internationally-recognised reference for research, innovation and translation in the application of engineering biology to microbial foods - demonstrating UK leadership in this field, attracting the best global talent, and delivering more sustainable, productive, resilient and healthy food systems.