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Moredun Research Institute

Moredun Research Institute

38 Projects, page 1 of 8
  • Funder: UK Research and Innovation Project Code: BB/T01315X/1
    Funder Contribution: 574,369 GBP

    Toxoplasma gondii is a parasite of cats that can infect all warm-blooded animals, including humans where it can cause severe disease in immune compromised people, such as AIDS or cancer patients, and in children who were infected in utero. The World Health Organisation and the Centre for Disease Control recognise toxoplasmosis as one of the most important foodborne diseases worldwide and a leading cause of death amongst foodborne illnesses. The disease also impacts the livestock sector where it is a major cause of abortion in sheep. There is considerable variation between different strains of the parasite with some being more pathogenic than others, particularly in South America where, worryingly, cases of severe disease have been reported in healthy, immune competent individuals. The high pathogenicity of some strains has sparked much research interest on T. gondii virulence to further our understanding of the host-parasite relationship as well as predict disease outcome. Although T. gondii is recognised as a major foodborne pathogen, there is a significant lack of data on the role of retail meat in the transmission of this parasite - something which was recently highlighted as a knowledge gap by the European Food Safety Authority. Meat consumption in Brazil is amongst the highest in the world so it is crucial to determine the role of meat in transmission of T. gondii particularly since more pathogenic strains dominate in this region. This project will address the knowledge gap by conducting the first ever comprehensive study of retail meat in Brazil, investigating incidence, viability and genetic diversity of T. gondii in different retail meat samples in São Paulo. Through collaboration between Brazil and the UK, it will be possible to assess the virulence of T. gondii isolated from meat products in a host-specific system to help determine the risk of different isolates to public and veterinary health. While the mouse has proven to be an extremely important model for research into T. gondii virulence, it remains unclear how these results extrapolate to other hosts, such as humans and sheep. Given the lack of evidence of a correlation between the severity of disease in mice compared to other animals, there is an urgent need for a more relevant, host-specific system for identifying host and pathogen factors involved in determining virulence and predicting disease outcome. This project aims to address this significant knowledge gap by investigating the host-pathogen interactions during acute infection of mouse, sheep and human cells with virulent and non-virulent strains of T. gondii in vitro. The project will also assess the applicability of 3D "mini guts" as in vitro host-specific models for investigating virulence, offering a unique and exciting experimental system which mimics the primary site of infection thereby reducing the reliance on experimental animals. Overall, this project will allow us to further our understanding of foodborne infections and parasite virulence. The development of a host-specific in vitro system to characterise virulence of T. gondii will offer a platform to investigate the mechanisms of virulence which will not only allow for the prediction of disease outcome in specific hosts, it will also aid vaccine design, a more specific treatment regime as well as the development of new drug compounds.

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  • Funder: UK Research and Innovation Project Code: BB/V019910/1
    Funder Contribution: 178,168 GBP

    Parasitic nematodes are amongst the most common pathogens in grazing ruminants worldwide. The continuous exposure to these worms has a significant impact on the health status and productivity of the animals. Control of these infections currently relies almost completely on periodic mass administration of anthelmintic drugs. However, with the increasing incidence of anthelmintic resistance around the world, there is an urgent need for alternative control measures. Vaccination is often put forward as the most rational and cost-effective alternative to control infections with parasitic worms. In recent years it has been shown that it is possible to protect cattle and sheep against worm infections by vaccinating them with proteins ("antigens") isolated directly from the worms. Unfortunately, for most parasite species, this approach is unsustainable for large-scale application as it relies on infected host animals to produce the vaccines. The production of synthetic vaccines seems the most obvious solution. However, of all the synthetic vaccines that were evaluated in the past, none induced sufficient levels of protection to consider further commercial development. One of the bottlenecks explaining why many vaccination trials with nematode vaccines have been unsuccessful is that the synthetic antigens in these vaccines are not decorated with the sugar (or "glycan") molecules that they would usually be covered with. Recent research has shown that the natural glycans present on the antigens can be critical in the context of vaccination as removal of the glycans from the antigens impaired the protective immune responses elicited by the vaccines. The glycans on a given protein can shape immune responses by influencing which receptors and cells of the immune system are targeted. In addition, nematode antigens carry very diverse and sometimes unique glycan structures, which can be highly immunogenic and major targets of the host's antibody responses. Therefore, reconstructing these glycan structures on synthetic nematode proteins may be key for successful vaccine development. Towards a flexible and sustainable solution to this problem significant progress has been made in recent years on adapting the protein production machinery of tobacco plants, such as Nicotiana benthamiana, allowing the synthesis of nematode antigens with a defined and tailored glycan composition. The aim of this project is to use this versatile plant-based production platform to express a set of well-defined nematode vaccine antigens and deliver proof-of-concept that efficacious vaccines can be produced if glycans are taken into account properly.

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  • Funder: UK Research and Innovation Project Code: BB/X016692/1
    Funder Contribution: 1,032,570 GBP

    Many infectious diseases affect livestock, impacting not only on the health and welfare of the animals but also on the economic sustainability of the agricultural sector and future food security. Ovine enzootic abortion (OEA) is an economically important endemic disease of worldwide significance in small ruminant species, caused by the Gram-negative bacterium Chlamydia abortus. In the UK it is the most common cause of infectious abortion in sheep, resulting in foetal death in the last 2-3 weeks of pregnancy or the delivery of weak offspring and causing losses in a flock of up to around 30%. Losses in the UK have been estimated to be around £25M per annum. The organism can also infect humans causing spontaneous abortion, and in whom infections can be life-threatening. Vaccination is currently considered the most effective way of controlling disease and vaccines based on inactivated or live whole-organisms are commercially available for use in small ruminants. However, live vaccines have been reported to cause infection and disease in some animals and inactivated vaccines have been found to have much lower effectiveness in protecting animals from infections. Thus, there is a need to develop safer, more effective vaccines for use in livestock. Reducing infection and disease burden in animals will also reduce the risk of infections in humans. In recent years, research has progressed into developing methods for manipulating the genomes of human chlamydial species, making use of an endogenous plasmid (DNA that is extra to that present on the chromosome) that many of the strains possess. These plasmids are also present in avian chlamydial species (Chlamydia psittaci) from which C. abortus evolved. However, no plasmid has been found to date in C. abortus strains. Recently, we have characterised the genome of a novel strain, designated 84/2334, which has been reclassified from C. psittaci to C. abortus and carries a plasmid. Therefore, this strain could potentially be used to develop a new C. abortus vaccine for controlling OEA. However, before doing this, we need to know how biologically similar the strain is to C. abortus and determine whether the strain causes infection and disease similar to that caused by C. abortus. In this project we will compare the growth dynamics of the 84/2334 strain in relation to both C. abortus and C. psittaci, investigate its growth cycle in the target host cell, identify the key molecules involved in causing pathogenesis, and determine its potential to cause infection and abortion. These studies will identify whether the strain is more similar to classical C. abortus than to C. psittaci and determine its suitability for use in future vaccine development studies.

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  • Funder: UK Research and Innovation Project Code: NE/X000303/1
    Funder Contribution: 30,935 GBP

    Many aspects of the natural world are changing under climate change. One of the most notable is that the timing of natural events - phenology - is changing, with many species becoming earlier in their activities each year. How are they doing this? There two main mechanisms: short-term reactions to circumstances within the lifetime of an individual, known as plasticity, and genetic change across generations due to natural selection, i.e. evolution. The role played by each of these mechanisms is important, because they enable different rates of response and have different potential for sustained change. For example plasticity can generate a very fast response, but species have limits to plasticity, whereas genetic change is slower but may be sustained over time. To date the most detailed studies of phenology change focus on egg lay dates in birds which must have an ample food supply to raise chicks and in which there is a sharp spring peak in food abundance. These studies conclude that the birds respond plastically to cues such a temperature that indicate there will soon be food, while there is little evidence of evolutionary change. But many species with different kinds of life history, most notably mammals that store nutrition and have a gestation period, are changing phenology just as fast as birds. Since they cannot fine-tune birth dates to conditions at birth, evolution is likely to be a more important mechanism in these species. In the individually-monitored red deer on Rum, several aspects of phenology have got earlier over time. For example calving date has got earlier by 14 days since 1980, and there is pilot evidence this is due to a combination of genetic change and plasticity. In this study we will investigate eights phenology traits by (1) Measuring plasticity to a range of weather and biological drivers (such as food availability and parasites); (2) Measuring natural selection and testing the hypothesis that selection favouring earlier phenology has strengthened with warming temperatures; (3) Predicting and measuring the evolutionary (by which we mean genetic) response to selection; (4) Predicting the population implications of changing phenology.

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  • Funder: UK Research and Innovation Project Code: BB/K002171/1
    Funder Contribution: 218,234 GBP

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

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