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1,222 Projects, page 1 of 123

  • UK Research and Innovation
  • UKRI|BBSRC
  • 2017

10
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  • Funder: UKRI Project Code: BB/L001187/1
    Funder Contribution: 210,407 GBP
    Partners: University of Essex

    Stomata are pores that provide for gaseous exchange across the impermeable cuticle of plant leaves. They open and close to balance the requirement for CO2 entry for photosynthesis against the need to reduce the transpiration of water vapour and prevent leaf drying. Stomatal transpiration is at the centre of a crisis in water availability and crop production that is expected to unfold over the next 20-30 years: globally, agricultural water usage has increased 6-fold in the past 100 years, twice as fast as the human population, and is projected to double again before 2030. Thus stomata represent an important target for breeders interested in manipulating crop performance. Stomatal movements are driven by solute transport - and consequent uptake/loss of water - across the cell membrane of the guard cells which surround the stomatal pore. Significantly, stomatal responses are slow compared to photosynthesis in the face of environmental fluctuations, especially of light. Improving water use efficiency (=amount of carbon fixed in photosynthesis/amount of water transpired) should be possible, without a cost to carbon assimilated in photosynthesis, if the speed of stomatal responses, especially to light, can be enhanced. However, the complexity of guard cell transport and its coupling to gas exchange and transpiration has presented a formidable barrier to systematic reverse-engineering aimed at enhancing stomatal responses through genetic manipulation and other means. Quantitative systems analysis offers an effective approach in silico to exploring the link between microscopic gene function and the macroscopic characteristics of assimilation and transpiration. As a first step to bridging this gap in understanding, we developed previously the OnGuard software for quantitative dynamic modelling of the guard cell. OnGuard models build explicitly on the wealth of molecular, biophysical and kinetic knowledge for guard cell transport and metabolism that drive stomatal movement; they accommodate stomata of different plant species, over the full range of conditions studied in the laboratory to date; and they have been shown to incorporate the real predictive power needed to guide experiments at the cellular and physiological levels that start with molecular manipulations in silico. The next major step towards establishing in silico strategies for crop design, based on our deep knowledge of stomatal guard cells, will be to establish and validate this computational link to incorporate carbon assimilation and water use efficiency at leaf and whole-plant levels. We propose now to develop such a strategy in models of the leaf, and scaling to the crop in the field, that capture CO2 uptake and transpiration. We will build the next-generation OnGuard models that incorporate CO2 uptake and transpiration, and we will incorporate computational statistical methods to accelerate model construction. Most important, the models will provide the essential micro-macro link to connect molecular function with physiological traits of the whole plant in water use and photosynthetic carbon assimilation and will enable scaling to the crop in the field. We will test this second generation of OnGuard models and validate their outputs to examine the longstanding hypothesis that significant erosion in the efficiency of water use by plants arises because of the mismatch in dynamic environmental responses between stomata and photosynthesis. Additionally, we will explore the connection of these traits with oscillations known to occur in stomatal aperture and in the signalling events (e.g. cytosolic-free [Ca2+]) previously documented at the cellular level in single guard cells. All studies will focus on the crop plant Vicia for which there is much data at the single-cell and whole-leaf levels, and on Arabidopsis for which we have mutants with well-defined effects on stomatal kinetics.

  • Funder: UKRI Project Code: BB/L003198/2
    Funder Contribution: 259,443 GBP
    Partners: JIC, Syngenta Ltd

    The European seed market is worth around £5 billion annually. Seed quality summarises the desirable characteristics of seeds sold on the market: they should germinate swiftly and evenly across a broad range of germination conditions, leading to a homogeneous stand of robust seedlings in the minimum length of time. These seedlings should establish a vigourous crop stand. Seed companies produce hybrid seeds in multiple sites globally, each subject to environmental variation between and within sites that can negatively impact seed quality. Across all species temperature variation during seed production is a major driver of variable seed quality, and breeding new varieties with robust seed quality in a range of production environments in now a key strategic goal of seed companies. A core goal of our research is to understand signalling pathways through which environmental variation during seed production affects seed quality traits, such as dormancy, germination and establishment vigour. Based on our recently published research and preliminary data we show that temperature during seed production has a major affect on seed behaviour through a signalling pathway that operates in the mother plant. This is a major new discovery as previously it has not been clear whether the developing seed itself is sensing the environment, or whether the mother plant senses the environment and somehow passes this information to the progeny seeds. We identify that the well known cold-sensing pathway that regulates tolerance to freezing also controls gene expression and physical properties of the seed coat that are known to be linked to changes in seed behaviour. The first part of the proposal aims to understand how temperature sensing leads to the plastic development, biochemistry and permeability of the seed coat, and how seed coat properties control seed behaviour. A major focus here is to understand how elements of the cold acclimation pathway and control of phenylpropanoid pathway gene expression known from experiments in vegetative tissues operate in maternal seed coat tissues and the nature of their targets in seeds. This requires intergrating knowledge from genetics molecular signalling and transcriptional control of secondary metabolism in seed coats. The second key section is to transfer this new knowledge from model to crop species, and for this we have developed a collaboration with Syngenta to assess and improve Brassica seed quality, a species where germination and establishment of seedlings varies according to seed production sites and seasons. We will examine control of seed quality in a panel of Brassica varieties with varying seed quality responses to maturation environmental conditions, and relate these to gene expression and the developmental, physical and biochemical properties of the seed coat. Finally we will delete genes in Brassica that we have shown control the transduction of temperature signals affecting seed quality in Arabidopsis. The goal here is to evaluate this technology for use in product development in seed companies, and collaboration with Syngenta will ensure exploitation of commercially useful germplasm. A key feature of our new seed technology is that seed quality of seed for sale can be controlled in hybrid seed from the genome of the mother plant rather than the zygote. This means that the properties of the seed sold and the crop seed can be independently controlled: in the future this will be useful in the many instances when high germination propensity of the crop is undesirable, such as to control sprouting in cereals, of fruit quality in glasshouse crops.

  • 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/J012157/1
    Funder Contribution: 1,930,310 GBP
    Partners: University of Exeter

    Rice provides 23% of calories consumed by mankind, and this figure is even higher in many developing countries. In fact, rice is the primary dietary staple for at least 70% of the world's poorest people. In Sub-Saharan Africa, most countries have adopted rice as a strategic crop in their food security policies in order to meet the needs of their growing urban populations. One of the biggest constraints on rice production in Sub-Saharan Africa is a devastating disease called rice blast. This disease can cause losses of up to 50% of the rice harvest in these regions, causing severe economic problems for farmers and leading to rice shortages and a greater need for importation of rice at high prices. This project aims to characterise populations of the pathogen that causes rice blast using genome sequencing, in order to determine its variability and capacity to cause disease on the most widely grown rice varieties. We then aim to use this knowledge to identify novel sources of resistance from world-wide rice stocks and, in particular, rice varieties especially bred to thrive in African growing conditions. We will then use modern, marker-assisted plant breeding approaches to create durably resistant rice varieties for use by growers in Sub-Saharan Africa. During the course of the project we will carry out training of four post-doctoral research fellows, who will spend significant amounts of time working in the region, and who will disseminate skills in molecular genetics, genomics and bioinformatics. We will also train two PhD students from Sub-Saharan Africa who will work in each member laboratory and receive training in modern genetic and genomic techniques applied to controlling one of the world's most devastating plant diseases.

  • Funder: UKRI Project Code: BB/K021168/1
    Funder Contribution: 30,612 GBP
    Partners: Imperial College London, Yale University

    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/K011502/1
    Funder Contribution: 93,520 GBP
    Partners: University of Southampton

    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: BB/L009846/1
    Funder Contribution: 692,419 GBP
    Partners: University of Oxford

    Proteins are polymers that are crucial to all aspects of life. Proteins are biologically produced polymers that are synthesised by polymerisation of monomeric amino acids. The template for the polymerisation process is messenger ribonucleic acid (mRNA), which in turn is encoded for by DNA, which is used for relatively long-term storage of information in the cells of all living organisms. However, once they have been synthesised, proteins can be further modified in processes that are often crucial for their physiological function. One such process is reaction with atmospheric oxygen, a small and high diffusible molecule. We are interested in defining how and why proteins react with oxygen from the atmosphere. In pioneering work it was found that atmospheric oxygen reacts with collagen, a material which helps cells to stick together in animals, in a reaction catalysed by oxygenases. Oxygenases are types of enzymes (or biological catalysts), that incorporate atmospheric oxygen into their reaction products. Many oxygenases use a metal, such as iron, to help capture oxygen. Subsequent to the discovery of its role in collagen biosynthesis, it was found that oxygenases play key roles in the production of antibiotics, such as the penicillins. More recently, we have found that oxygenases also catalyse the hydroxylation of proteins. Some of the protein targets of oxygenases are important from biological and medicinal perspectives. A breakthrough was the discovery that the physiological mechanism by which cells in animals respond to limiting oxygen is actually regulated by oxygenase catalysed hydroxylation of proteins, involved in regulating the conversion of DNA to mRNA. Following this discovery we, and others, have found other protein-hydroxylases, acting on a range of protein-residues. We are now in an exceptionally good position to work out how these enzymes work, including developing an understanding of how they bind their protein substrates. We will use crystallographic and other techniques, that will provide detailed information on how the enzymes work as machines. The structural and mechanistic studies will lay the groundwork in order to exploit the basic science to artificially alter the activity of the oxygenases, using them for the production of high-value modified proteins, and to provide knowledge that will be useful for the pharmaceutical industry in targeting them for diseases. Overall the work will enable the United Kingdom to remain at the forefront of basic science research on oxygenases and the exploitation of this research for the development of new medicines and catalysts for high value chemical production.

  • Funder: UKRI Project Code: BB/L019442/1
    Funder Contribution: 356,371 GBP
    Partners: University of Portsmouth

    The human immune system plays a vital role in protecting our bodies from disease. It is a complex combination of specialized cells and proteins that recognize and kill bacteria and viruses. It is also extremely effective in recognizing and eliminating normal cells that may be sick or damaged. A key protein that we all have in our blood is called serum amyloid P component (SAP). A closely related protein (CRP) is better known as an inflammatory marker that is routinely tested by doctors in blood samples of patients with suspected infection or inflammation. Much research has been performed to understand the role of SAP in numerous diseases especially protein folding conditions (such as systemic amyloidosis), and amyloid-related diseases that principally affect the brain, such as Creutzfeld-Jacob disease (CJD) and Alzheimer's, however we know very little about the normal function of SAP. A major discovery was that SAP binds to DNA - the component of our cells that contains our genetic information. However, because SAP is normally found in our blood rather than inside cells where the DNA is normally located, it is believed that SAP scavenges DNA that is released into our blood from diseased or damaged cells. This is of critical importance, because it prevents the immune system from attacking our normal DNA, which can have disastrous consequences (such as in the disease systemic lupus erythematosus (SLE)). As well as binding to DNA, the applicant and others have shown that SAP binds to a number of important targets including RNA - another critically important molecule normally found in our cells. Other important binding targets of SAP include bacteria, the extracellular matrix (a supporting scaffold for cells and tissues) and a wide range of immune proteins and cells. The full significance of these other interactions is yet to be determined. The aim of this project is to determine how SAP binds to DNA at the molecular level. The applicant has successfully performed preliminary experiments making initial mutants of SAP in collaboration with the Oxford Protein Production Facility (OPPF). Now, in pilot studies with colleagues in Portsmouth who are experts in DNA-protein interactions, the applicant has determined how tightly SAP binds to DNA sequences and, for the first time, to RNA. We are poised to identify the sections of SAP responsible for binding to the various targets by mutating parts of the SAP molecule. This fundamental research work will help us understand various human conditions linked to ageing. Furthermore, by understanding more about how this protein works, we can determine whether it is a suitable drug target for diseases such as Alzheimer's, SLE and rheumatoid arthritis. Perhaps even more exciting is the possibility that by acting as a DNA scavenger, SAP prevents DNA vaccination working in humans. By understanding more about how SAP recognizes DNA, this work could significantly contribute towards the development of new and safer vaccines.

  • Funder: UKRI Project Code: BB/L000288/1
    Funder Contribution: 313,936 GBP
    Partners: SRUC

    The 54 billion chickens produced each year for their meat (broilers) provide a third of global meat consumption. Chicken provides high quality protein, preventing human malnutrition and with the global demand for meat growing as people become richer, chicken meat plays an important role in food security. Chicken is also efficient to produce requiring lower food inputs per kg produced, reducing its carbon footprint compared to other meats. Because of scientific breeding methods, broiler chickens now grow 3 times faster than they did 50 years ago, reaching their 2.5 kg slaughter weight as juveniles at just 6 weeks old. This success has come at a welfare cost to the parents of broilers, known as broiler breeders (estimated 350 million birds per year globally). Broiler breeders reach sexual maturity at 20 weeks and reproduce until 60 weeks of age. Because they have almost the same potential for rapid growth as broilers, they must be food restricted to control their growth, otherwise they become obese, infertile, and unhealthy and many would die. But with their food ration restricted to one-third of what they could eat, broiler breeders finish their food in minutes and then pace, forage and peck at non-food objects, and will work hard to get more food. All of which suggests they are suffering negative welfare in terms of hunger. The fact that both generous and restricted feeding result in welfare problems creates an ethical dilemma known as 'the broiler breeder paradox'. One potential solution is to restrict growth ensuring good health but reduce hunger by providing a more 'filling' food. Adding dietary fibre makes food less energy-dense, so a larger volume of food results in the same total energy intake. This food takes longer to eat and digest, and behaviour appears more normal, but does it reduce hunger and improve welfare? This project aims to help us answer this question. As well as watching how behaviour is changed by different diets, we will use two new approaches to measure the welfare impact of broiler breeder hunger: 1) A foraging motivation test which measures how much the bird wants to forage (peck and scratch) in a new location without providing food. Because no food is provided, this test measures hunger without affecting it. 2) Measuring the body's systems in the gut (nerve signals and hormones) and in a part of the brain which control eating behaviour (the hypothalamus), where our focus will be on a substance called agouti-related protein (AGRP). We have shown that AGRP can be used as a measure of hunger in chickens: AGRP depends on the amount of food eaten in both the long-term (over several weeks) and the short term (in the last few days). We also suspect, based on a small experiment, that restricting growth using a high fibre diet might reduce AGRP compared to the usual rationed food. We will apply these measures in combination to ask the following questions: 1) How do our different measures of hunger vary, meal to meal and over the day? 2) How is hunger affected by adding dietary fibre to reduce energy density? 3) How are different signals about 'fullness' from the chickens' gut integrated by the brain? In the final part (4) we will apply what we have learnt. We will test whether new broiler breeder diets developed by an international poultry breeding company can reduce hunger and improve welfare. Our project will therefore help the chicken industry to respond to the ethical concerns in society over a difficult aspect of animal welfare. Finally, as food intake regulation is largely similar in birds and mammals, our findings will be of interest to those aiming to reduce obesity in humans. In particular, our investigation of dietary changes to reduce energy intake while promoting 'fullness' and reducing hunger, is relevant to 'dieting' for weight loss in humans.

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1,222 Projects, page 1 of 123
  • Funder: UKRI Project Code: BB/L001187/1
    Funder Contribution: 210,407 GBP
    Partners: University of Essex

    Stomata are pores that provide for gaseous exchange across the impermeable cuticle of plant leaves. They open and close to balance the requirement for CO2 entry for photosynthesis against the need to reduce the transpiration of water vapour and prevent leaf drying. Stomatal transpiration is at the centre of a crisis in water availability and crop production that is expected to unfold over the next 20-30 years: globally, agricultural water usage has increased 6-fold in the past 100 years, twice as fast as the human population, and is projected to double again before 2030. Thus stomata represent an important target for breeders interested in manipulating crop performance. Stomatal movements are driven by solute transport - and consequent uptake/loss of water - across the cell membrane of the guard cells which surround the stomatal pore. Significantly, stomatal responses are slow compared to photosynthesis in the face of environmental fluctuations, especially of light. Improving water use efficiency (=amount of carbon fixed in photosynthesis/amount of water transpired) should be possible, without a cost to carbon assimilated in photosynthesis, if the speed of stomatal responses, especially to light, can be enhanced. However, the complexity of guard cell transport and its coupling to gas exchange and transpiration has presented a formidable barrier to systematic reverse-engineering aimed at enhancing stomatal responses through genetic manipulation and other means. Quantitative systems analysis offers an effective approach in silico to exploring the link between microscopic gene function and the macroscopic characteristics of assimilation and transpiration. As a first step to bridging this gap in understanding, we developed previously the OnGuard software for quantitative dynamic modelling of the guard cell. OnGuard models build explicitly on the wealth of molecular, biophysical and kinetic knowledge for guard cell transport and metabolism that drive stomatal movement; they accommodate stomata of different plant species, over the full range of conditions studied in the laboratory to date; and they have been shown to incorporate the real predictive power needed to guide experiments at the cellular and physiological levels that start with molecular manipulations in silico. The next major step towards establishing in silico strategies for crop design, based on our deep knowledge of stomatal guard cells, will be to establish and validate this computational link to incorporate carbon assimilation and water use efficiency at leaf and whole-plant levels. We propose now to develop such a strategy in models of the leaf, and scaling to the crop in the field, that capture CO2 uptake and transpiration. We will build the next-generation OnGuard models that incorporate CO2 uptake and transpiration, and we will incorporate computational statistical methods to accelerate model construction. Most important, the models will provide the essential micro-macro link to connect molecular function with physiological traits of the whole plant in water use and photosynthetic carbon assimilation and will enable scaling to the crop in the field. We will test this second generation of OnGuard models and validate their outputs to examine the longstanding hypothesis that significant erosion in the efficiency of water use by plants arises because of the mismatch in dynamic environmental responses between stomata and photosynthesis. Additionally, we will explore the connection of these traits with oscillations known to occur in stomatal aperture and in the signalling events (e.g. cytosolic-free [Ca2+]) previously documented at the cellular level in single guard cells. All studies will focus on the crop plant Vicia for which there is much data at the single-cell and whole-leaf levels, and on Arabidopsis for which we have mutants with well-defined effects on stomatal kinetics.

  • Funder: UKRI Project Code: BB/L003198/2
    Funder Contribution: 259,443 GBP
    Partners: JIC, Syngenta Ltd

    The European seed market is worth around £5 billion annually. Seed quality summarises the desirable characteristics of seeds sold on the market: they should germinate swiftly and evenly across a broad range of germination conditions, leading to a homogeneous stand of robust seedlings in the minimum length of time. These seedlings should establish a vigourous crop stand. Seed companies produce hybrid seeds in multiple sites globally, each subject to environmental variation between and within sites that can negatively impact seed quality. Across all species temperature variation during seed production is a major driver of variable seed quality, and breeding new varieties with robust seed quality in a range of production environments in now a key strategic goal of seed companies. A core goal of our research is to understand signalling pathways through which environmental variation during seed production affects seed quality traits, such as dormancy, germination and establishment vigour. Based on our recently published research and preliminary data we show that temperature during seed production has a major affect on seed behaviour through a signalling pathway that operates in the mother plant. This is a major new discovery as previously it has not been clear whether the developing seed itself is sensing the environment, or whether the mother plant senses the environment and somehow passes this information to the progeny seeds. We identify that the well known cold-sensing pathway that regulates tolerance to freezing also controls gene expression and physical properties of the seed coat that are known to be linked to changes in seed behaviour. The first part of the proposal aims to understand how temperature sensing leads to the plastic development, biochemistry and permeability of the seed coat, and how seed coat properties control seed behaviour. A major focus here is to understand how elements of the cold acclimation pathway and control of phenylpropanoid pathway gene expression known from experiments in vegetative tissues operate in maternal seed coat tissues and the nature of their targets in seeds. This requires intergrating knowledge from genetics molecular signalling and transcriptional control of secondary metabolism in seed coats. The second key section is to transfer this new knowledge from model to crop species, and for this we have developed a collaboration with Syngenta to assess and improve Brassica seed quality, a species where germination and establishment of seedlings varies according to seed production sites and seasons. We will examine control of seed quality in a panel of Brassica varieties with varying seed quality responses to maturation environmental conditions, and relate these to gene expression and the developmental, physical and biochemical properties of the seed coat. Finally we will delete genes in Brassica that we have shown control the transduction of temperature signals affecting seed quality in Arabidopsis. The goal here is to evaluate this technology for use in product development in seed companies, and collaboration with Syngenta will ensure exploitation of commercially useful germplasm. A key feature of our new seed technology is that seed quality of seed for sale can be controlled in hybrid seed from the genome of the mother plant rather than the zygote. This means that the properties of the seed sold and the crop seed can be independently controlled: in the future this will be useful in the many instances when high germination propensity of the crop is undesirable, such as to control sprouting in cereals, of fruit quality in glasshouse crops.

  • 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/J012157/1
    Funder Contribution: 1,930,310 GBP
    Partners: University of Exeter

    Rice provides 23% of calories consumed by mankind, and this figure is even higher in many developing countries. In fact, rice is the primary dietary staple for at least 70% of the world's poorest people. In Sub-Saharan Africa, most countries have adopted rice as a strategic crop in their food security policies in order to meet the needs of their growing urban populations. One of the biggest constraints on rice production in Sub-Saharan Africa is a devastating disease called rice blast. This disease can cause losses of up to 50% of the rice harvest in these regions, causing severe economic problems for farmers and leading to rice shortages and a greater need for importation of rice at high prices. This project aims to characterise populations of the pathogen that causes rice blast using genome sequencing, in order to determine its variability and capacity to cause disease on the most widely grown rice varieties. We then aim to use this knowledge to identify novel sources of resistance from world-wide rice stocks and, in particular, rice varieties especially bred to thrive in African growing conditions. We will then use modern, marker-assisted plant breeding approaches to create durably resistant rice varieties for use by growers in Sub-Saharan Africa. During the course of the project we will carry out training of four post-doctoral research fellows, who will spend significant amounts of time working in the region, and who will disseminate skills in molecular genetics, genomics and bioinformatics. We will also train two PhD students from Sub-Saharan Africa who will work in each member laboratory and receive training in modern genetic and genomic techniques applied to controlling one of the world's most devastating plant diseases.

  • Funder: UKRI Project Code: BB/K021168/1
    Funder Contribution: 30,612 GBP
    Partners: Imperial College London, Yale University

    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/K011502/1
    Funder Contribution: 93,520 GBP
    Partners: University of Southampton

    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: BB/L009846/1
    Funder Contribution: 692,419 GBP
    Partners: University of Oxford

    Proteins are polymers that are crucial to all aspects of life. Proteins are biologically produced polymers that are synthesised by polymerisation of monomeric amino acids. The template for the polymerisation process is messenger ribonucleic acid (mRNA), which in turn is encoded for by DNA, which is used for relatively long-term storage of information in the cells of all living organisms. However, once they have been synthesised, proteins can be further modified in processes that are often crucial for their physiological function. One such process is reaction with atmospheric oxygen, a small and high diffusible molecule. We are interested in defining how and why proteins react with oxygen from the atmosphere. In pioneering work it was found that atmospheric oxygen reacts with collagen, a material which helps cells to stick together in animals, in a reaction catalysed by oxygenases. Oxygenases are types of enzymes (or biological catalysts), that incorporate atmospheric oxygen into their reaction products. Many oxygenases use a metal, such as iron, to help capture oxygen. Subsequent to the discovery of its role in collagen biosynthesis, it was found that oxygenases play key roles in the production of antibiotics, such as the penicillins. More recently, we have found that oxygenases also catalyse the hydroxylation of proteins. Some of the protein targets of oxygenases are important from biological and medicinal perspectives. A breakthrough was the discovery that the physiological mechanism by which cells in animals respond to limiting oxygen is actually regulated by oxygenase catalysed hydroxylation of proteins, involved in regulating the conversion of DNA to mRNA. Following this discovery we, and others, have found other protein-hydroxylases, acting on a range of protein-residues. We are now in an exceptionally good position to work out how these enzymes work, including developing an understanding of how they bind their protein substrates. We will use crystallographic and other techniques, that will provide detailed information on how the enzymes work as machines. The structural and mechanistic studies will lay the groundwork in order to exploit the basic science to artificially alter the activity of the oxygenases, using them for the production of high-value modified proteins, and to provide knowledge that will be useful for the pharmaceutical industry in targeting them for diseases. Overall the work will enable the United Kingdom to remain at the forefront of basic science research on oxygenases and the exploitation of this research for the development of new medicines and catalysts for high value chemical production.

  • Funder: UKRI Project Code: BB/L019442/1
    Funder Contribution: 356,371 GBP
    Partners: University of Portsmouth

    The human immune system plays a vital role in protecting our bodies from disease. It is a complex combination of specialized cells and proteins that recognize and kill bacteria and viruses. It is also extremely effective in recognizing and eliminating normal cells that may be sick or damaged. A key protein that we all have in our blood is called serum amyloid P component (SAP). A closely related protein (CRP) is better known as an inflammatory marker that is routinely tested by doctors in blood samples of patients with suspected infection or inflammation. Much research has been performed to understand the role of SAP in numerous diseases especially protein folding conditions (such as systemic amyloidosis), and amyloid-related diseases that principally affect the brain, such as Creutzfeld-Jacob disease (CJD) and Alzheimer's, however we know very little about the normal function of SAP. A major discovery was that SAP binds to DNA - the component of our cells that contains our genetic information. However, because SAP is normally found in our blood rather than inside cells where the DNA is normally located, it is believed that SAP scavenges DNA that is released into our blood from diseased or damaged cells. This is of critical importance, because it prevents the immune system from attacking our normal DNA, which can have disastrous consequences (such as in the disease systemic lupus erythematosus (SLE)). As well as binding to DNA, the applicant and others have shown that SAP binds to a number of important targets including RNA - another critically important molecule normally found in our cells. Other important binding targets of SAP include bacteria, the extracellular matrix (a supporting scaffold for cells and tissues) and a wide range of immune proteins and cells. The full significance of these other interactions is yet to be determined. The aim of this project is to determine how SAP binds to DNA at the molecular level. The applicant has successfully performed preliminary experiments making initial mutants of SAP in collaboration with the Oxford Protein Production Facility (OPPF). Now, in pilot studies with colleagues in Portsmouth who are experts in DNA-protein interactions, the applicant has determined how tightly SAP binds to DNA sequences and, for the first time, to RNA. We are poised to identify the sections of SAP responsible for binding to the various targets by mutating parts of the SAP molecule. This fundamental research work will help us understand various human conditions linked to ageing. Furthermore, by understanding more about how this protein works, we can determine whether it is a suitable drug target for diseases such as Alzheimer's, SLE and rheumatoid arthritis. Perhaps even more exciting is the possibility that by acting as a DNA scavenger, SAP prevents DNA vaccination working in humans. By understanding more about how SAP recognizes DNA, this work could significantly contribute towards the development of new and safer vaccines.

  • Funder: UKRI Project Code: BB/L000288/1
    Funder Contribution: 313,936 GBP
    Partners: SRUC

    The 54 billion chickens produced each year for their meat (broilers) provide a third of global meat consumption. Chicken provides high quality protein, preventing human malnutrition and with the global demand for meat growing as people become richer, chicken meat plays an important role in food security. Chicken is also efficient to produce requiring lower food inputs per kg produced, reducing its carbon footprint compared to other meats. Because of scientific breeding methods, broiler chickens now grow 3 times faster than they did 50 years ago, reaching their 2.5 kg slaughter weight as juveniles at just 6 weeks old. This success has come at a welfare cost to the parents of broilers, known as broiler breeders (estimated 350 million birds per year globally). Broiler breeders reach sexual maturity at 20 weeks and reproduce until 60 weeks of age. Because they have almost the same potential for rapid growth as broilers, they must be food restricted to control their growth, otherwise they become obese, infertile, and unhealthy and many would die. But with their food ration restricted to one-third of what they could eat, broiler breeders finish their food in minutes and then pace, forage and peck at non-food objects, and will work hard to get more food. All of which suggests they are suffering negative welfare in terms of hunger. The fact that both generous and restricted feeding result in welfare problems creates an ethical dilemma known as 'the broiler breeder paradox'. One potential solution is to restrict growth ensuring good health but reduce hunger by providing a more 'filling' food. Adding dietary fibre makes food less energy-dense, so a larger volume of food results in the same total energy intake. This food takes longer to eat and digest, and behaviour appears more normal, but does it reduce hunger and improve welfare? This project aims to help us answer this question. As well as watching how behaviour is changed by different diets, we will use two new approaches to measure the welfare impact of broiler breeder hunger: 1) A foraging motivation test which measures how much the bird wants to forage (peck and scratch) in a new location without providing food. Because no food is provided, this test measures hunger without affecting it. 2) Measuring the body's systems in the gut (nerve signals and hormones) and in a part of the brain which control eating behaviour (the hypothalamus), where our focus will be on a substance called agouti-related protein (AGRP). We have shown that AGRP can be used as a measure of hunger in chickens: AGRP depends on the amount of food eaten in both the long-term (over several weeks) and the short term (in the last few days). We also suspect, based on a small experiment, that restricting growth using a high fibre diet might reduce AGRP compared to the usual rationed food. We will apply these measures in combination to ask the following questions: 1) How do our different measures of hunger vary, meal to meal and over the day? 2) How is hunger affected by adding dietary fibre to reduce energy density? 3) How are different signals about 'fullness' from the chickens' gut integrated by the brain? In the final part (4) we will apply what we have learnt. We will test whether new broiler breeder diets developed by an international poultry breeding company can reduce hunger and improve welfare. Our project will therefore help the chicken industry to respond to the ethical concerns in society over a difficult aspect of animal welfare. Finally, as food intake regulation is largely similar in birds and mammals, our findings will be of interest to those aiming to reduce obesity in humans. In particular, our investigation of dietary changes to reduce energy intake while promoting 'fullness' and reducing hunger, is relevant to 'dieting' for weight loss in humans.

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