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1,473 Projects, page 1 of 148

  • UK Research and Innovation
  • UKRI|BBSRC
  • 2015

10
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  • Funder: UKRI Project Code: BBS/E/I/00002120
    Funder Contribution: 21,909 GBP
    Partners: Pirbright Institute

    Diseases of domestic livestock are an ever present threat to the challenge of feeding an increasing global population. African swine fever virus has existed in a natural cycle between warthogs and soft ticks for millennia, but causes a lethal, highly contagious, haemorrhagic fever in domestic swine and wild boar. In 2007, African swine fever was introduced into Georgia, probably through contaminated waste from a ship, and since has spread throughout most of European Russia and has now been reported in Poland, Lithuania, Latvia and Estonia. Effective vaccines against African swine fever are desperately needed. Autophagy is a highly conserved intracellular pathway that has evolved to breakdown and recycle damaged cytoplasmic components by delivering them to lysosomes. Autophagy can also be induced in response to physiological stress, most notably that of starvation (The word autophagy literally means self-eat in Greek). Many important responses to infection are dependent on the autophagy pathway and pathogens have evolved mechanisms to manipulate autophagy for their own benefit. Recent experiments have demonstrated that disrupting the ability of viruses to inhibit autophagy can enhance immune responses. We have shown that African swine fever virus can block part of the autophagy pathway, raising the possibility that deletion of viral proteins that inhibit autophagy may enhance the immunogenicity of a live attenuated ASFV vaccine. The major aims of this project are to further characterise the effect of African swine fever virus infection on the autophagy pathway, identify novel autophagy inhibitors in the African swine fever genome and generate recombinant viruses lacking these genes. The findings from these studies will contribute to the development of safe and effective, live attenuated ASFV vaccine candidates.

  • Funder: UKRI Project Code: BB/L026759/1
    Funder Contribution: 30,561 GBP
    Partners: University of Aberdeen, University of Western Sydney

    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.

  • Funder: UKRI Project Code: BB/N503915/1
    Funder Contribution: 103,042 GBP
    Partners: University of London, GlaxoSmithKline PLC

    Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

  • Funder: UKRI Project Code: 1658348
    Partners: University of Aberdeen

    This project aims to develop clinical diets for use in aquaculture, with a specific focus on alleviating the symptoms of gill diseases, such as amoebic gill disease (AGD). The work falls within the BBSRC strategic priorities of animal health/agriculture and food security, welfare of managed animals and science excellence. Specifically, this research aims to optimise an intervention strategy to combat an endemic infectious disease that currently reduces the health and welfare of farmed Atlantic salmon in the UK. AGD, caused by the parasitic protist Neoparamoeba perurans, is an emerging disease of salmon. The disease was reported in Tasmania in the 1980's and has now spread to other major salmon farming countries such as Chile, Norway and the UK. AGD can severely damage fish gills, resulting in poor growth and mortalities. AGD-infected fish are often susceptible to secondary infections of bacteria, viruses and sea lice. With salmon the largest food export for Scotland, with an estimated retail value of >1billion pounds sterling worldwide, this research strives to help maintain a supply of healthy fish for the table. The proposed research builds upon previous collaborations on fish nutrition and immunity between the Scottish Fish Immunology Research Centre (SFIRC) and EWOS Innovation, including previous joint PhD student supervision. SFIRC is a world renowned centre for studies into fish immunology and EWOS a leader in the fish feed industry. Both partners benefit from the collaboration: SFIRC by access to novel diet formulations and access to experimental facilities and field trials run by EWOS, EWOS by access to cutting edge research into fish immunology with direct relevance to the pathology associated with AGD. The partners have the necessary expertise/facilities to achieve the project goals, and the supervisors have an excellent track record of successful PhD student supervision. A two pronged approach to clinical diet assessment and optimisation for use with AGD will be adopted. In the first existing diets used to reduce the pathology of chronic viral diseases will be tested to assess impact on AGD-induced pathology and the host immune response elicited post-treatment and post-exposure to the disease at farm sites. In the second assessment of anti-protozoal defences will be carried out, and these results fed back into diet development to target such responses. Any promising new diet formulations will be field tested, with access to farm trials arranged by EWOS. Research training will be given to the student throughout the programme. At Aberdeen the student will be exposed to an academic environment typical of a research University, where cutting edge research is undertaken in a wide range of biological disciplines, and where multidisciplinary/ cross-disciplinary research is commonplace. In yr 1 induction to topics such as research ethics & governance, safety, risk assessment, record keeping will be given and immediate training needs assessed. In house training will be given for methods and use of equipment, with sign off once appropriate standards are met. In later years training for transferable and employability skills will be given with courses on report writing, oral presentation, project management, maximizing impact, interpersonal skills and being assertive, and interviewing skills. The student will visit the EWOS premises each year, to gain an understanding of the fish diet business and trial protocol preparations. A 3 month placement in yr 2 is planned, to help with setting up and sampling of the trials, with the potential for a further placement in yr 3. At EWOS the student will be integrated into an existing project-based management structure and will be an integral member of a defined project team, giving immediate access to other scientists specialised in statistics, trials design, nutrition, and veterinary science. This will facilitate training, skills development and effective knowledge transfer.

  • Funder: UKRI Project Code: BB/M021343/1
    Funder Contribution: 390,338 GBP
    Partners: Babraham Institute

    The mechanisms by which infections elicit antibody responses have been recognised as one of fundamental importance for over a century. We now understand that many different cell types collaborate to enable antibody formation, and for the generation of immunological memory - the underpinning principle of vaccine efficacy. Antibodies are produced by specialised cells called antibody secreting plasma cells (ASC). These develop from cells called B lymphocytes. The process of development is promoted by another type of cell called the helper T lymphocyte and inhibited by a third type of cell called the regulatory T lymphocyte. Other cell types are involved, but the balance between the helper and the regulatory T cell is the ultimate determinant of the response. During infection by salmonella bacteria a robust antibody response is generated by ASC and both helper and regulatory T cells play a role here. The frequency and potency of the helper and regulatory T cells response is mediated by signalling pathways that arise from receptors on the T lymphocyte cell surface. One component of this signalling process is an enzyme called phosphatidylinositol 3-kinase (PI3K)-specifically the gene encoding the p110d subunit. This enzyme controls many processes in cells and acts a coordinator to regulate cell number and potency. The goal of our research project is to understand the basic molecular mechanisms by which PI3K achieves this. We have already identified one pathway that PI3K inhibits in order to promote helper T cell function and we want to gain a more detailed understanding of which components of this pathway PI3K acts on. We have identified additional molecules that are good candidates for regulation by PI3K and we want to confirm these and identify if and how they join up with the pathways we think are important. Finally, we want to test a new molecular mechanism that we believe will be important for helper T cells to function well. To do this we will employ novel technology that has never been used on T lymphocytes. This new technology will provide insight into how genes that are encoded in the DNA are converted into proteins that makes cells work.

  • Funder: UKRI Project Code: BB/N005279/1
    Funder Contribution: 389,910 GBP
    Partners: University of Warwick

    The economic importance of seed plants cannot be overstated, as they are our main sources of food, fibre and other industrial raw materials. However, our capacity to generate sufficient food, animal feed and energy is increasingly compromised by human population expansion, competition for land use, rapid biodiversity loss and predicted global climate change. The process of sexual reproduction in higher plants is of particular importance for the aim of increasing crop yields, overcoming hybridization barriers and selecting and fixing quality traits. Before we can develop tools to manipulate plant reproduction in our favour we must achieve a deeper understanding of the basic mechanisms underlying gamete development and double fertilization mechanisms in angiosperms. The project will deliver the first comprehensive view of the molecular evolution of plant sexual reproduction and will provide insights into the origins of double fertilization in flowering plants. In addition, gene expression data and the networks generated will be valuable in understanding the evolution of biological pathways and gene function prediction beyond the focus on reproduction in this project. In parallel, the work on crop species will identify genes useful to the agricultural industry to enable precision control of plant reproduction, to overcome hybridization barriers and to promote better breeding schemes by improving hybrid seed production.

  • Funder: UKRI Project Code: BB/M009203/1
    Funder Contribution: 514,066 GBP
    Partners: University of London

    We rely on our immune systems to keep us alive in the face of constant challenges from infections. Because we never know what each infection will look like we generate an immune system that contains many millions of different cells each capable of recognising different infections. Whilst this solves the problem of being able to recognise a vast array of different bacteria and viruses, it creates a second problem which is that those same immune cells can now also recognise bits of our bodies causing disease. Controlling our immune system so that it only attacks invaders and not our bodies is critical and getting it wrong can be fatal. Understanding how the immune system achieves this balance is relevant to most areas of our health. Understanding the mechanism underpinning this balance is the basis of this proposal. To understand this process we need to focus on proteins found at the interface between two types of immune cell, the T cell and the dendritic cell which are responsible for initiating a response. The T cell expresses two proteins, CD28 which acts as a "go" signal and CTLA-4 which inhibits this process. Surprisingly, both CD28 and CTLA-4 interact with the same proteins called CD80 and CD86. We recently discovered that CTLA-4 acts like a tiny hoover and can remove CD80 and CD86 molecules from the surface of dendritic cells using an unusual process called transendocytosis. By hoovering up CD80 and CD86 this means that there is effectively a competition between CD28 and CTLA-4. Removing all the ligands prevents CD28 from receiving a "go" signal keeping our immune system switched off. In this proposal we are seeking to understand exactly how the CTLA-4 hoover functions and by doing this better understand situations where the process goes wrong. To perform this work we will use several approaches: 1) We will take apart the CTLA-4 protein in order to figure out which bits are necessary for it to work. 2) We will find our which parts of the cell interact with CTLA-4 in order to promote transendocytosis. 3) We will used advanced microscopy to visualise CTLA-4 interacting with its cellular partners to understand the time and place where transendocytosis occurs. 4) We will test our predictions to see whether interfering with selected parts of the CTLA-4 hoover mechanism cause defects in our immune system as we expect. Together these experiments will provide a complete picture of both an unusual process in biology and a better understanding of how an essential part of our immune system works.

  • Funder: UKRI Project Code: BB/M025551/1
    Funder Contribution: 440,942 GBP
    Partners: University of Edinburgh

    Changes in the light environment, caused by encroaching vegetation or seasonal progression, can alter the course of development leading to a wide variety of plant architectures. This developmental "plasticity", is a defining characteristic of plants and a prerequisite for survival, allowing adaptation to an environment in flux. Adaptive responses to nearby vegetation are often crucial in the natural environment but costly in terms of yield in a field crop. Indeed, the ability to control crop architecture in dense canopy field conditions is a priority for plant breeders. Speaking to this need, the outputs from this project will generate novel targets and predictive tools that can be used to improve plant architecture in vegetation rich environments. The project aims to fill a knowledge gap: even though light constantly tunes plant development it is still unclear how this is executed at the cellular and molecular levels. A principal aim will be to establish how light signalling is coupled to development providing the first detailed understanding of how light drives plant growth plasticity. Plants continue to grow and develop through their life cycle and so have to maintain an active stem cell pool. In the shoot, stem cells reside in the "meristem" which is located at the shoot apex. New organ (e.g. leaf) production is controlled by a suite of developmental genes that act at the shoot apex. Our earlier work and that of others showed that light controls the rate of leaf production, leaf size and morphology, suggesting light regulates meristem function. More recently we have uncovered molecular evidence that strongly reinforces this proposition. The research programme aims to delineate the molecular path from light activated signal transduction to organogenesis, providing the first account of how light directs development. To help resolve molecular connections, that may be intricate, we will employ an integrated modelling and experimental regime. This is possible as we have already developed light signalling model framework that can be extended to incorporate meristem genes. Model simulation of different pathway structures will allow us to predict new molecular connections that can be tested in the lab. This iterative process will facilitate and improve the accuracy of pathway assembly. The model will help us to determine how different light regimes alter pathway dynamics and development, providing a system level understanding of pathway behaviour. An important outcome will be the production of a developmental plasticity model with predictive capabilities: an invaluable resource for crop improvement programmes. Model development also represents an important step toward our future aim to construct a virtual plant.

  • Funder: UKRI Project Code: BB/L025477/1
    Funder Contribution: 67,392 GBP
    Partners: NTU

    About 60% of the population have fasting blood cholesterol concentrations high enough to be a risk factor for coronary heart disease, which is responsible for the deaths of >60,000 people annually in the UK, many of which are potentially preventable with appropriate changes to diet and lifestyle. Water soluble types of dietary fibre (SDF), confer many health benefits; in particular, oat and barley beta-glucan (BG) is effective at reducing blood cholesterol and lipid concentrations and this has been recognised by European Food Safety Authority (EFSA). However, further processing of BG in foods can reduce its efficacy, and so a recommended intake of BG of at least 3 g/day requires large quantities (>100g) of unprocessed cereals such as oats and barley to be consumed daily. Most consumers would find this difficult or unpalatable, so approaches are required to incorporate BG into palatable, commonly consumed foods with demonstrable blood cholesterol and lipid lowering properties. Despite the clear health benefits of BG, its mechanisms of action are still not well understood. It has been suggested that the ability of BG to lower cholesterol is triggered by the interference of this polymer and other types of SDF with various stages of lipid digestion, thus reducing or delaying lipid uptake. This then disturbs the recycling of bile salts (bio-surfactants produced by the liver which aid lipid digestion) from the gut back into the liver. Bile salts are cholesterol derivatives, so increased production of bile salts in the liver could reduce plasma cholesterol concentrations. It is not clear which aspects of lipid digestion are affected by BG, and therefore which molecular properties are crucial for its functionality. The aim of this proposal is to determine the mechanisms of action of SDF and in particular BG on lipid digestion. Various mechanisms have been proposed, and they mostly involve the lipid digestion and transport processes. Therefore in vitro lipid digestion studies will allow us to study in detail all the different stages of lipid digestion including lipase activity and adsorption, bile salt adsorption and transport, and micelle formation and transport. The molecular and biochemical properties of BG and other other types of SDF will be determined using a range of state of the art techniques, including analytical centrifugation, and will allow us to determine which properties are important for functionality. Based on these findings, the effect of processing on BG will be studied to determine exactly why processing attenuates its ability to reduce blood cholesterol and lipids. This knowledge will then allow us to propose strategies by which SDF can be incorporated into palatable, manufactured foods and still retain their ability to reduce blood cholesterol and lipid concentrations.

  • Funder: UKRI Project Code: BB/M017583/1
    Funder Contribution: 150,617 GBP
    Partners: University of Exeter, Anglesey Aquaculture Ltd

    The current FLIP proposal builds upon an existing BBSRC Industrial Partnership Award in collaboration with Skretting (the largest global producer of aquaculture feed). The existing project is based on a novel manipulation of diets that has already been demonstrated to improve the efficiency of converting food into growth by a remarkable 20 % under laboratory conditions. It uses laboratory studies with live fish to assess the energetic costs and health implications of feeding in aquaculture fish, and then to design optimal diet compositions to minimise these costs. It aims to make energetic savings for the fish in particular regarding acid-base and salt balance following a meal, and minimise how these natural disturbances impact upon respiratory gas exchange and excretory processes. The present FLIP proposal will use similar approaches to the above current BBSRC-funded project. However, whereas the current BBSRC-IPA project addresses dietary issues, this FLIP proposal specifically addresses newly discovered water quality changes that are particularly associated with intensive recirculating aquaculture systems (RAS). The present FLIP proposal seeks to use a 2-way interchange between academia and industry to address previously unconsidered factors that can have a major influence on the biology and efficiency of growth in fish. By facilitating an interchange of academic and industrial personnel between their respective sites this project aims to address these non-ideal changes in water chemistry associated with intensive recirculating aquaculture systems (RAS). It aims to establish (and ideally prevent) previously unrecognised energetic costs for fish caused by these water quality issues that can impair health, welfare, growth and ultimately the production efficiency in aquaculture. It is a collaboration with Anglesey Aquaculture Ltd (AAL), the largest marine RAS in Europe and the UK's only farm for seabass, a high value and commercially important fish. This form of land-based aquaculture is increasingly promoted worldwide due to its sustainability in terms of low water use and minimising environmental problems from waste products. However, the intensity of the aquaculture conditions creates water quality problems that must be countered, primarily a consumption of oxygen and excretion of carbon dioxide by the fish. This is compensated by large scale aeration of the recirculating water which effectively restores oxygen, but is often insufficient to removal all the animal's waste carbon dioxide which subsequently acidifies the water. To deal with this pH problem RAS operators added huge amounts of alkali (1-2 tonnes of caustic soda per day) at considerable cost. However, this pH compensation measure is now realised to create further water quality issues, specifically high alkalinity and low calcium within the water. These secondary changes are known to impair the physiology and energetics of fish, and are therefore suspecting of negatively impacting their feeding and growth. By facilitating a 2-way transfer of knowledge and skills (via direct secondments of one academic and one industry interchanger, at each other's site), this FLIP project aims to provide a cost-effective, evidence-based solution(s) to these specific water quality issues. Furthermore, we aim to embed a culture of problem-solving through academic-industrial collaboration into the fabric of both organisations such that future problems associated with sustainable production of fish can be avoided or mitigated in a timely fashion.

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1,473 Projects, page 1 of 148
  • Funder: UKRI Project Code: BBS/E/I/00002120
    Funder Contribution: 21,909 GBP
    Partners: Pirbright Institute

    Diseases of domestic livestock are an ever present threat to the challenge of feeding an increasing global population. African swine fever virus has existed in a natural cycle between warthogs and soft ticks for millennia, but causes a lethal, highly contagious, haemorrhagic fever in domestic swine and wild boar. In 2007, African swine fever was introduced into Georgia, probably through contaminated waste from a ship, and since has spread throughout most of European Russia and has now been reported in Poland, Lithuania, Latvia and Estonia. Effective vaccines against African swine fever are desperately needed. Autophagy is a highly conserved intracellular pathway that has evolved to breakdown and recycle damaged cytoplasmic components by delivering them to lysosomes. Autophagy can also be induced in response to physiological stress, most notably that of starvation (The word autophagy literally means self-eat in Greek). Many important responses to infection are dependent on the autophagy pathway and pathogens have evolved mechanisms to manipulate autophagy for their own benefit. Recent experiments have demonstrated that disrupting the ability of viruses to inhibit autophagy can enhance immune responses. We have shown that African swine fever virus can block part of the autophagy pathway, raising the possibility that deletion of viral proteins that inhibit autophagy may enhance the immunogenicity of a live attenuated ASFV vaccine. The major aims of this project are to further characterise the effect of African swine fever virus infection on the autophagy pathway, identify novel autophagy inhibitors in the African swine fever genome and generate recombinant viruses lacking these genes. The findings from these studies will contribute to the development of safe and effective, live attenuated ASFV vaccine candidates.

  • Funder: UKRI Project Code: BB/L026759/1
    Funder Contribution: 30,561 GBP
    Partners: University of Aberdeen, University of Western Sydney

    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.

  • Funder: UKRI Project Code: BB/N503915/1
    Funder Contribution: 103,042 GBP
    Partners: University of London, GlaxoSmithKline PLC

    Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

  • Funder: UKRI Project Code: 1658348
    Partners: University of Aberdeen

    This project aims to develop clinical diets for use in aquaculture, with a specific focus on alleviating the symptoms of gill diseases, such as amoebic gill disease (AGD). The work falls within the BBSRC strategic priorities of animal health/agriculture and food security, welfare of managed animals and science excellence. Specifically, this research aims to optimise an intervention strategy to combat an endemic infectious disease that currently reduces the health and welfare of farmed Atlantic salmon in the UK. AGD, caused by the parasitic protist Neoparamoeba perurans, is an emerging disease of salmon. The disease was reported in Tasmania in the 1980's and has now spread to other major salmon farming countries such as Chile, Norway and the UK. AGD can severely damage fish gills, resulting in poor growth and mortalities. AGD-infected fish are often susceptible to secondary infections of bacteria, viruses and sea lice. With salmon the largest food export for Scotland, with an estimated retail value of >1billion pounds sterling worldwide, this research strives to help maintain a supply of healthy fish for the table. The proposed research builds upon previous collaborations on fish nutrition and immunity between the Scottish Fish Immunology Research Centre (SFIRC) and EWOS Innovation, including previous joint PhD student supervision. SFIRC is a world renowned centre for studies into fish immunology and EWOS a leader in the fish feed industry. Both partners benefit from the collaboration: SFIRC by access to novel diet formulations and access to experimental facilities and field trials run by EWOS, EWOS by access to cutting edge research into fish immunology with direct relevance to the pathology associated with AGD. The partners have the necessary expertise/facilities to achieve the project goals, and the supervisors have an excellent track record of successful PhD student supervision. A two pronged approach to clinical diet assessment and optimisation for use with AGD will be adopted. In the first existing diets used to reduce the pathology of chronic viral diseases will be tested to assess impact on AGD-induced pathology and the host immune response elicited post-treatment and post-exposure to the disease at farm sites. In the second assessment of anti-protozoal defences will be carried out, and these results fed back into diet development to target such responses. Any promising new diet formulations will be field tested, with access to farm trials arranged by EWOS. Research training will be given to the student throughout the programme. At Aberdeen the student will be exposed to an academic environment typical of a research University, where cutting edge research is undertaken in a wide range of biological disciplines, and where multidisciplinary/ cross-disciplinary research is commonplace. In yr 1 induction to topics such as research ethics & governance, safety, risk assessment, record keeping will be given and immediate training needs assessed. In house training will be given for methods and use of equipment, with sign off once appropriate standards are met. In later years training for transferable and employability skills will be given with courses on report writing, oral presentation, project management, maximizing impact, interpersonal skills and being assertive, and interviewing skills. The student will visit the EWOS premises each year, to gain an understanding of the fish diet business and trial protocol preparations. A 3 month placement in yr 2 is planned, to help with setting up and sampling of the trials, with the potential for a further placement in yr 3. At EWOS the student will be integrated into an existing project-based management structure and will be an integral member of a defined project team, giving immediate access to other scientists specialised in statistics, trials design, nutrition, and veterinary science. This will facilitate training, skills development and effective knowledge transfer.

  • Funder: UKRI Project Code: BB/M021343/1
    Funder Contribution: 390,338 GBP
    Partners: Babraham Institute

    The mechanisms by which infections elicit antibody responses have been recognised as one of fundamental importance for over a century. We now understand that many different cell types collaborate to enable antibody formation, and for the generation of immunological memory - the underpinning principle of vaccine efficacy. Antibodies are produced by specialised cells called antibody secreting plasma cells (ASC). These develop from cells called B lymphocytes. The process of development is promoted by another type of cell called the helper T lymphocyte and inhibited by a third type of cell called the regulatory T lymphocyte. Other cell types are involved, but the balance between the helper and the regulatory T cell is the ultimate determinant of the response. During infection by salmonella bacteria a robust antibody response is generated by ASC and both helper and regulatory T cells play a role here. The frequency and potency of the helper and regulatory T cells response is mediated by signalling pathways that arise from receptors on the T lymphocyte cell surface. One component of this signalling process is an enzyme called phosphatidylinositol 3-kinase (PI3K)-specifically the gene encoding the p110d subunit. This enzyme controls many processes in cells and acts a coordinator to regulate cell number and potency. The goal of our research project is to understand the basic molecular mechanisms by which PI3K achieves this. We have already identified one pathway that PI3K inhibits in order to promote helper T cell function and we want to gain a more detailed understanding of which components of this pathway PI3K acts on. We have identified additional molecules that are good candidates for regulation by PI3K and we want to confirm these and identify if and how they join up with the pathways we think are important. Finally, we want to test a new molecular mechanism that we believe will be important for helper T cells to function well. To do this we will employ novel technology that has never been used on T lymphocytes. This new technology will provide insight into how genes that are encoded in the DNA are converted into proteins that makes cells work.

  • Funder: UKRI Project Code: BB/N005279/1
    Funder Contribution: 389,910 GBP
    Partners: University of Warwick

    The economic importance of seed plants cannot be overstated, as they are our main sources of food, fibre and other industrial raw materials. However, our capacity to generate sufficient food, animal feed and energy is increasingly compromised by human population expansion, competition for land use, rapid biodiversity loss and predicted global climate change. The process of sexual reproduction in higher plants is of particular importance for the aim of increasing crop yields, overcoming hybridization barriers and selecting and fixing quality traits. Before we can develop tools to manipulate plant reproduction in our favour we must achieve a deeper understanding of the basic mechanisms underlying gamete development and double fertilization mechanisms in angiosperms. The project will deliver the first comprehensive view of the molecular evolution of plant sexual reproduction and will provide insights into the origins of double fertilization in flowering plants. In addition, gene expression data and the networks generated will be valuable in understanding the evolution of biological pathways and gene function prediction beyond the focus on reproduction in this project. In parallel, the work on crop species will identify genes useful to the agricultural industry to enable precision control of plant reproduction, to overcome hybridization barriers and to promote better breeding schemes by improving hybrid seed production.

  • Funder: UKRI Project Code: BB/M009203/1
    Funder Contribution: 514,066 GBP
    Partners: University of London

    We rely on our immune systems to keep us alive in the face of constant challenges from infections. Because we never know what each infection will look like we generate an immune system that contains many millions of different cells each capable of recognising different infections. Whilst this solves the problem of being able to recognise a vast array of different bacteria and viruses, it creates a second problem which is that those same immune cells can now also recognise bits of our bodies causing disease. Controlling our immune system so that it only attacks invaders and not our bodies is critical and getting it wrong can be fatal. Understanding how the immune system achieves this balance is relevant to most areas of our health. Understanding the mechanism underpinning this balance is the basis of this proposal. To understand this process we need to focus on proteins found at the interface between two types of immune cell, the T cell and the dendritic cell which are responsible for initiating a response. The T cell expresses two proteins, CD28 which acts as a "go" signal and CTLA-4 which inhibits this process. Surprisingly, both CD28 and CTLA-4 interact with the same proteins called CD80 and CD86. We recently discovered that CTLA-4 acts like a tiny hoover and can remove CD80 and CD86 molecules from the surface of dendritic cells using an unusual process called transendocytosis. By hoovering up CD80 and CD86 this means that there is effectively a competition between CD28 and CTLA-4. Removing all the ligands prevents CD28 from receiving a "go" signal keeping our immune system switched off. In this proposal we are seeking to understand exactly how the CTLA-4 hoover functions and by doing this better understand situations where the process goes wrong. To perform this work we will use several approaches: 1) We will take apart the CTLA-4 protein in order to figure out which bits are necessary for it to work. 2) We will find our which parts of the cell interact with CTLA-4 in order to promote transendocytosis. 3) We will used advanced microscopy to visualise CTLA-4 interacting with its cellular partners to understand the time and place where transendocytosis occurs. 4) We will test our predictions to see whether interfering with selected parts of the CTLA-4 hoover mechanism cause defects in our immune system as we expect. Together these experiments will provide a complete picture of both an unusual process in biology and a better understanding of how an essential part of our immune system works.

  • Funder: UKRI Project Code: BB/M025551/1
    Funder Contribution: 440,942 GBP
    Partners: University of Edinburgh

    Changes in the light environment, caused by encroaching vegetation or seasonal progression, can alter the course of development leading to a wide variety of plant architectures. This developmental "plasticity", is a defining characteristic of plants and a prerequisite for survival, allowing adaptation to an environment in flux. Adaptive responses to nearby vegetation are often crucial in the natural environment but costly in terms of yield in a field crop. Indeed, the ability to control crop architecture in dense canopy field conditions is a priority for plant breeders. Speaking to this need, the outputs from this project will generate novel targets and predictive tools that can be used to improve plant architecture in vegetation rich environments. The project aims to fill a knowledge gap: even though light constantly tunes plant development it is still unclear how this is executed at the cellular and molecular levels. A principal aim will be to establish how light signalling is coupled to development providing the first detailed understanding of how light drives plant growth plasticity. Plants continue to grow and develop through their life cycle and so have to maintain an active stem cell pool. In the shoot, stem cells reside in the "meristem" which is located at the shoot apex. New organ (e.g. leaf) production is controlled by a suite of developmental genes that act at the shoot apex. Our earlier work and that of others showed that light controls the rate of leaf production, leaf size and morphology, suggesting light regulates meristem function. More recently we have uncovered molecular evidence that strongly reinforces this proposition. The research programme aims to delineate the molecular path from light activated signal transduction to organogenesis, providing the first account of how light directs development. To help resolve molecular connections, that may be intricate, we will employ an integrated modelling and experimental regime. This is possible as we have already developed light signalling model framework that can be extended to incorporate meristem genes. Model simulation of different pathway structures will allow us to predict new molecular connections that can be tested in the lab. This iterative process will facilitate and improve the accuracy of pathway assembly. The model will help us to determine how different light regimes alter pathway dynamics and development, providing a system level understanding of pathway behaviour. An important outcome will be the production of a developmental plasticity model with predictive capabilities: an invaluable resource for crop improvement programmes. Model development also represents an important step toward our future aim to construct a virtual plant.

  • Funder: UKRI Project Code: BB/L025477/1
    Funder Contribution: 67,392 GBP
    Partners: NTU

    About 60% of the population have fasting blood cholesterol concentrations high enough to be a risk factor for coronary heart disease, which is responsible for the deaths of >60,000 people annually in the UK, many of which are potentially preventable with appropriate changes to diet and lifestyle. Water soluble types of dietary fibre (SDF), confer many health benefits; in particular, oat and barley beta-glucan (BG) is effective at reducing blood cholesterol and lipid concentrations and this has been recognised by European Food Safety Authority (EFSA). However, further processing of BG in foods can reduce its efficacy, and so a recommended intake of BG of at least 3 g/day requires large quantities (>100g) of unprocessed cereals such as oats and barley to be consumed daily. Most consumers would find this difficult or unpalatable, so approaches are required to incorporate BG into palatable, commonly consumed foods with demonstrable blood cholesterol and lipid lowering properties. Despite the clear health benefits of BG, its mechanisms of action are still not well understood. It has been suggested that the ability of BG to lower cholesterol is triggered by the interference of this polymer and other types of SDF with various stages of lipid digestion, thus reducing or delaying lipid uptake. This then disturbs the recycling of bile salts (bio-surfactants produced by the liver which aid lipid digestion) from the gut back into the liver. Bile salts are cholesterol derivatives, so increased production of bile salts in the liver could reduce plasma cholesterol concentrations. It is not clear which aspects of lipid digestion are affected by BG, and therefore which molecular properties are crucial for its functionality. The aim of this proposal is to determine the mechanisms of action of SDF and in particular BG on lipid digestion. Various mechanisms have been proposed, and they mostly involve the lipid digestion and transport processes. Therefore in vitro lipid digestion studies will allow us to study in detail all the different stages of lipid digestion including lipase activity and adsorption, bile salt adsorption and transport, and micelle formation and transport. The molecular and biochemical properties of BG and other other types of SDF will be determined using a range of state of the art techniques, including analytical centrifugation, and will allow us to determine which properties are important for functionality. Based on these findings, the effect of processing on BG will be studied to determine exactly why processing attenuates its ability to reduce blood cholesterol and lipids. This knowledge will then allow us to propose strategies by which SDF can be incorporated into palatable, manufactured foods and still retain their ability to reduce blood cholesterol and lipid concentrations.

  • Funder: UKRI Project Code: BB/M017583/1
    Funder Contribution: 150,617 GBP
    Partners: University of Exeter, Anglesey Aquaculture Ltd

    The current FLIP proposal builds upon an existing BBSRC Industrial Partnership Award in collaboration with Skretting (the largest global producer of aquaculture feed). The existing project is based on a novel manipulation of diets that has already been demonstrated to improve the efficiency of converting food into growth by a remarkable 20 % under laboratory conditions. It uses laboratory studies with live fish to assess the energetic costs and health implications of feeding in aquaculture fish, and then to design optimal diet compositions to minimise these costs. It aims to make energetic savings for the fish in particular regarding acid-base and salt balance following a meal, and minimise how these natural disturbances impact upon respiratory gas exchange and excretory processes. The present FLIP proposal will use similar approaches to the above current BBSRC-funded project. However, whereas the current BBSRC-IPA project addresses dietary issues, this FLIP proposal specifically addresses newly discovered water quality changes that are particularly associated with intensive recirculating aquaculture systems (RAS). The present FLIP proposal seeks to use a 2-way interchange between academia and industry to address previously unconsidered factors that can have a major influence on the biology and efficiency of growth in fish. By facilitating an interchange of academic and industrial personnel between their respective sites this project aims to address these non-ideal changes in water chemistry associated with intensive recirculating aquaculture systems (RAS). It aims to establish (and ideally prevent) previously unrecognised energetic costs for fish caused by these water quality issues that can impair health, welfare, growth and ultimately the production efficiency in aquaculture. It is a collaboration with Anglesey Aquaculture Ltd (AAL), the largest marine RAS in Europe and the UK's only farm for seabass, a high value and commercially important fish. This form of land-based aquaculture is increasingly promoted worldwide due to its sustainability in terms of low water use and minimising environmental problems from waste products. However, the intensity of the aquaculture conditions creates water quality problems that must be countered, primarily a consumption of oxygen and excretion of carbon dioxide by the fish. This is compensated by large scale aeration of the recirculating water which effectively restores oxygen, but is often insufficient to removal all the animal's waste carbon dioxide which subsequently acidifies the water. To deal with this pH problem RAS operators added huge amounts of alkali (1-2 tonnes of caustic soda per day) at considerable cost. However, this pH compensation measure is now realised to create further water quality issues, specifically high alkalinity and low calcium within the water. These secondary changes are known to impair the physiology and energetics of fish, and are therefore suspecting of negatively impacting their feeding and growth. By facilitating a 2-way transfer of knowledge and skills (via direct secondments of one academic and one industry interchanger, at each other's site), this FLIP project aims to provide a cost-effective, evidence-based solution(s) to these specific water quality issues. Furthermore, we aim to embed a culture of problem-solving through academic-industrial collaboration into the fabric of both organisations such that future problems associated with sustainable production of fish can be avoided or mitigated in a timely fashion.

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