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Infestation of the skin with Psoroptes Ovis (sheep scab mite) represents a major animal welfare and economic burden on the sheep industry. A prototype sheep scab vaccine is effective at controlling sheep scab with an efficacy of over 80% (lesion size reduction). However, the development of a vaccine was considered a ‘market failure.’ The ever-decreasing amount of treatment options means sustainable control approaches are becoming more attractive.

Bovine Respiratory Disease (BRD) in cattle remains a significant problem in the beef and dairy industries. BRD is caused by a variety of infectious agents. Most outbreaks start with viral infection. The key viruses involved in the disease are respiratory syncytial virus (BRSV), parainfluenza 3 virus (PI3V), bovine herpesvirus 1 (BHV-1) and bovine viral diarrhoea virus (BVDV). BRD is still a significant problem despite several vaccines and medications being commercially available. This suggests these options are not sufficiently effective.

BVDV eradication in Scotland has progressed well and is no longer an issue. Vaccines for the other viruses are moderately protective against disease but ineffective in controlling the spread of disease. Modified live vaccines induce broader, more complete immune responses. However, viral proteins have evolved to significantly interfere with the immune response. Further, modified live virus vaccine strains of BHV-1 can appear in vaccinated animals and, when reactivated reduce the immune response. Similar latency and reversion issues appear for virulence bovine respiratory syncytial virus.

In sum, there are several key challenges related to:

• Overcoming the limitations of the current chemotherapeutics; reduced efficacy and antibiotic resistance; and the effects of residues on the environment, operator, and food safety.
• Providing increased productivity and efficiency in livestock production with the economic, food security and environmental benefits which accrue from that.

Plants sustain life, mitigate climate change, enrich landscapes, and underpin our rural industries. However, they are subject to an ever-increasing range of pest and disease threats. The drivers of these threats are travel, the globalisation of trade, and the effects of climate change.

It is vital to protect the health and quality of Scotland’s major crops (barley, potatoes, and soft fruit) from the wide range of endemic diseases. We need to reduce our dependency on crop protection chemicals due to pesticide resistance and concerns around impacts on biodiversity. We must therefore develop innovative and effective non-chemical controls that support sustainable ecosystem management and agricultural reform.

Phytophthora species (cause of the disease Potato late blight) infect plant species across agriculture, horticulture, forestry, and the natural environment. Blight infections are difficult to manage, making them one of Scotland’s key plant health threats. Potato Cyst Nematode (PCN) causes significant yield losses, and the amount of infested agricultural land increases every year. If the current loss of land continues, our £100 million seed potato industry will be in jeopardy in the next 30 years.

Scotland’s soft fruit industry supports the rural economy. There is also a need to future-proof the sector in the face of many plant disease challenges. There are considerable threats to the sector posed by Spotted Winged Drosophila (SWD), Brown Marmorated Stink Bug, and Phytophthora root rot, to name a few. It has never been more important that we better understand, detect, and manage these pests and diseases to support the sector in producing high-quality, healthy, and marketable crops.

As the interim report of the EU Mission Board for Soil health and food states “Soils provide us with nutritious food and other products as well as with clean water and flourishing habitats for biodiversity. At the same time, soils can help slow the onset of climate change and make us more resilient to extreme climate events such as droughts and floods. Soils preserve our cultural heritage and are a key part of the landscapes that we all cherish. Simply put, healthy living soils keep us, and the world around us, alive.”

There is an imperative to protect soils, improve soil health and identify the roles and contributions of Scotland’s soils in delivering key beneficial services. However, there is currently a lack of knowledge of the mechanistic understanding of how the complex interactions of soil deliver individual and interlinked functions. Also, the definition of soil function and the determination of its boundaries is not a simple task. Soil functions are described as the flows and transformations of mass, energy, and genetic information that connect soil to the wider critical zone, transmitting the impacts of human activity at the land surface and providing a control point for beneficial human intervention. As a result, the soil functional outcome is a result of interactions among physical, chemical, biological including human factors.

Further advances in knowledge are required to understand

• How complex soil interactions and functions can continue to provide societal benefits

• How to protect soils through the development of new management practices

• To support the monitoring of Scotland’s soil health and measure the vulnerability of Scottish soils to existing and future perturbations

• To offer nature-based solutions for the remediation and protection of soil

Improving the detection and diagnosis of infectious, endemic diseases is a key step to reducing the impacts on animal health and welfare. This enables the implementation of appropriate control measures and integrated management strategies. In addition, the targeted use of existing veterinary products via informed diagnostic decisions can reduce their unnecessary use, limiting environmental contamination and prolonging their efficacy for the future. This will generate positive impacts on the productivity, efficiency, and economic impact of livestock production. Over the long-term, this will improve the sustainability of the Scottish livestock sector. The wider public will directly benefit through increased food safety and security and improved animal welfare.

The key challenges for this project are:

• Current endemic disease diagnostics lack accuracy and specificity
• Developing diagnostic tools that can detect resistance to drugs used to control disease in livestock as well as new and emerging infections
• Exploiting novel technologies to develop new and improved diagnostic platforms

One of the critical challenges for veterinary and human medicine is the evolution of pathogens resistant to multiple drugs and antimicrobials previously used to treat them. The problem is compounded by the carriage of antimicrobial resistance (AMR) genes on mobile DNA. Transfer of these genes between distinct bacteria from different sources contributes to the environmental spread of AMR. For example, we have found that Campylobacter isolates from animals carry identical tetracycline resistance genes to human commensal bacteria, located on the same mobile DNA. This provides strong evidence for the spread of genes between diverse bacteria from diverse environments.

The concern is that zoonotic pathogens and emerging bacterial diseases may carry multiple drug resistance genes that can spread between livestock and human commensal microbiota, and be acquired by other pathogens. Such transfer of AMR genes between bacteria is impacted by environmental factors including antimicrobial use, the presence of heavy metals and other biocides. It is crucial to understand the effects of external factors on gene evolution and transfer, which allows us to identify risk factors affecting transmission of genes, and the bacteria carrying them, between the environment, animals, and humans.

We do not know:

• Whether the commensal microbiome - the community of gut microbes living in our intestine - is a reservoir of transferable AMR genes
• Whether the same resistance genes and bacteria, are widely distributed in samples obtained from diverse environments
• The frequencies and mechanisms by which AMR genes transfer in both directions between gut, environmental and pathogenic bacteria
• The transmission pathways of AMR genes between bacteria
• How co-selection factors including antimicrobials and heavy metals influence the co-carriage and spread of multiple resistance genes

For the important infections and diseases affecting Scottish livestock production, we do not have a full understanding of how the pathogens are distributed or transmitted to their host animal, what key pathogens and components are important for infection and disease, and how these components interact with the host immune system. Two major diseases affecting cattle production in Scotland are bovine pneumonic pasteurellosis and Johne’s disease.

Pneumonic pasteurellosis 

Pneumonic pasteurellosis is caused by Pasteurella multocida and results in significant production losses and mortality. No vaccines are available in Europe. Live vaccines in the United States provide a short duration of immunity and may exacerbate the disease. Extensive pulmonary damage occurs before clinical signs are evident. Therefore, an effective vaccine would offer more opportunities to instigate treatment to prevent lung damage.

Johne’s Disease

Johne’s Disease (JD) is caused by Mycobacterium avium subspecies paratuberculosis (MAP) and affects cattle, sheep, and goats. Ruminants often become infected in their first few months of life, via contaminated teats or the mother’s milk. MAP is shed in the faeces of infected livestock as well as wildlife reservoirs, contaminating the surrounding soil, water, and surfaces.

Infection can go undetected due to limited diagnostic testing. The current vaccine is only appropriate for sheep and does not stop infection or transmission. However, we can use it successfully as part of a JD control programme to mitigate introduction and spread in flocks. MAP is also controversially associated with Crohn’s disease in humans and so represents a potential public health threat.

Clinical mastitis 

Intramammary infections causing mastitis are other important production-associated diseases in ruminants. Clinical mastitis is an important animal welfare issue and can lead to death or premature culling. It causes a reduction in milk quantity and quality, which influences weight gain and lamb production. Another pathogen affecting sheep productivity is Jaagsiekte retrovirus (JSRV), the cause of Ovine Pulmonary Adenocarcinoma (OPA), a contagious tumour of sheep. OPA remains a significant disease problem in the UK and worldwide. Disease control is problematic without a test for JSRV infection. Transthoracic ultrasound scanning (TUS) is an effective way to diagnose pre-clinical OPA, but it is expensive.

Infectious diseases continue to be a significant problem in farmed animals. Diseases such as enteritis, mastitis and uterine infections cause livestock suffering and financial losses for farmers. These issues are made more challenging by the rising prevalence of pathogens with antimicrobial resistance and the need to reduce antibiotic usage on farms. We need novel treatment options, therefore, to reduce the growth and prevalence of pathogens such as toxigenic Escherichia coli to reduce the burden of infectious disease in livestock.

One highly promising avenue is to harness the indigenous microbes (microbiome) of livestock to enhance their defence against invading pathogens. The microbiome protects the host animal via a range of activities, including stimulating the immune system and producing antimicrobial compounds that kill or impede disease-causing microbes. The susceptibility of animals to infectious diseases can therefore be heavily influenced by the composition of their gut microbiome. However, the microbiomes of livestock are complex, and many of the constituent species have either yet to be cultured or are vastly understudied. As a result, it is largely unknown what components of livestock microbiomes are likely to be the most active against pathogens, and that can be developed as novel therapeutic options. In this project, we are therefore aiming to identify livestock microbes, or their products, with inhibitory activity against a range of important pathogens.

Most infectious agents affecting livestock enter the body or reside on mucosal surfaces of the gut, lung and nasal tracts, and mammary gland. Mucosal surfaces are lined by epithelial cells, provide a barrier against infectious agents, and play a key role in initiating immune responses. Researching these interactions is critically important for developing novel ways to control infections. However, developing studies can be technically challenging due to: (i) the inaccessibility of most mucosal surfaces for studies within the animal; (ii) available epithelial cell culture systems do not accurately reflect the range of cell types present in vivo, nor the morphology of the epithelial surface. There is a need to generate more relevant epithelial culture models which represent the in vivo epithelium.

A key development in this area in recent years has been the ability to generate epithelial organoids from epithelial stem cells, which form three-dimensional tissue constructs that mimic the corresponding in vivo epithelium in terms of morphology and cell types. These organoid cultures consist of a central lumen lined by epithelial cells, although they can be altered to allow the apical (luminal facing) surface of the epithelium to be on the outside of the organoid (‘apical-out’ organoids). These organoids can be passaged in vitro and cryopreserved, meaning that multiple experiments can be performed from organoids generated from a single individual. This greatly reduces the number of animals required for host-pathogen studies, in line with the 3Rs principles (Replacement, Reduction and Refinement).

Epithelium additionally plays a key role in alerting the immune system to infection, either by producing signalling molecules to activate and recruit immune cells, or uptake of antigens via microfold or M-cells. These cells are highly specialised in the uptake of particulate antigens from the luminal surface which are then sampled by sub-epithelial antigen-presenting cells (APCs). M-cells are located within the follicle-associated epithelium (FAE) overlying organised lymphoid tissue within the mucosa, known as Mucosa Associated Lymphoid Tissue (MALT). It is both here and in draining lymph nodes that APC present antigen to mucosal T cells to initiate the adaptive (antigen-specific) immune response. In cattle and sheep, MALT is concentrated in specific mucosal sites, including nasal, bronchial, intestinal, and rectal mucosa. These sites represent key targets for vaccines aimed at inducing strong mucosal immune responses, which may be key for several pathogens.

New, emerging, and endemic pests and pathogens are threatening Scotland’s key crops and industries. Cereals represent 65% of arable production in Scotland, with 800,000 tonnes of malting barley a year being used for whisky distillation. The challenge is to meet the expected 20% increase in demand over the next five years. Scotland produces 1.3 million tonnes of potatoes every year (valued at £250 million), 42% of which are grown for seed, with a £55 million export value. Soft fruit growers produce 30,000 tonnes of berries, which are undergoing an exponential increase in sales, contributing approximately £150 million to the economy. A wide range of pests and diseases negatively affect quality and yield in these key Scottish crops and therefore carry a significant economic and environmental burden.

Prevention and mitigation of pest and disease outbreaks are affected by drivers including travel, globalisation of trade, and the effects of climate change. The exploitation of new markets will bring new export trade rules and an increased risk of importing new pests and diseases into Scotland, with associated implications for plant health resilience. The challenge is to tailor strategies to individual pest, pathogen and crop systems and the local environment, whilst delivering at the field and farm scale. We need robust scientific evidence, tools, and strategies to underpin plant health resilience, policy decisions and the uptake of effective integrated pest management (IPM) strategies.

Novel Crops: To address opportunities for producing alternative protein and carbohydrate crops in Scottish agriculture for fish and crustacean feed, bioenergy, bio-refining, animal feed and human consumption, and to develop design criteria for integrating suitable alternative legume and non-legume crops as sole and intercrops within rotations whilst also accounting for agronomic and ecosystem services.

There are two main areas of research:

1. Nitrogen use efficiency, novel high protein crops and the multiple benefits that arise from innovatively managed cropped systems, and especially legume (i.e. biological nitrogen fixation) supported cropping for more sustainable food, feed and energy production, including novel food and feed formulations. Additionally, this work aims to improve production efficiency of biomass crops (e.g the grass Miscanthus) particularly for marginal land by identifying combinations of Miscanthus and associated plant growth promoting rhizobacteria best suited for these cropping situations.
2. Novel fruit, floral and flora-based crops and associated novel cropping strategies, with the aim of strengthening the Scottish economy via sustainable use of underutilised natural resources. These include the identification of the best agronomic practices for under-cover production of dwarf hop varieties to help support the development of the rapidly expanding craft micro-brewery businesses in Scotland and establishment of a collection of wild Scottish low bush berry populations to characterise genetic types and identify best-fit for purpose populations and practices to underpin their commercial development. Finally, the work aims to identify several native Scottish plant species and their bioactives (extracted chemicals that affect biological processes) which show a high potential to improve health and which are also suitable for large scale in-field commercial production.