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54 Projects

  • Canada
  • 2020
  • 2022

10
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  • Funder: UKRI Project Code: EP/V043811/1
    Funder Contribution: 497,214 GBP

    Coronaviruses are transmitted from an infectious individual through large respiratory droplets generated by coughing, sneezing or speaking. These infectious droplets are then transmitted to the mucosal surfaces of a recipient through inhalation of the aerosol or by contact with contaminated fomites such as surfaces or other objects. In healthcare settings, personal protective equipment (PPE) plays a crucial role in interrupting the transmission of highly communicable diseases such as COVID19 from patients to healthcare workers (HCWs). However, research has shown that PPE can also act as a fomite during the donning and doffing process as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive on these surfaces for up to three days. This creates a need for more effective PPE materials that can provide antiviral protection. In this proposal we aim to develop a dual action antiviral/antifouling coating to lower the risk of transmission of the SARS-CoV-2 to HCWs from COVID19 patients. This project will deliver antiviral/antifouling coatings that can be readily applied to PPE surfaces such as faceshields that are likely to encounter a high level of viral load and would be of great benefit to the health of clinical staff. Furthermore, this project has embedded into its planning a rapid pathway for optimisation, translation, and upscaling of manufacture to deliver a low-cost technology within a short timescale.

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  • Funder: UKRI Project Code: NE/V010131/1
    Funder Contribution: 7,776 GBP

    NERC: Jennifer Watts: NE/S007504/1

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  • Funder: NSF Project Code: 1907243
    Funder Contribution: 138,000 USD
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  • Funder: UKRI Project Code: NE/V010034/1
    Funder Contribution: 9,100 GBP

    NERC : Zoe Melvin : NE/L002604/1 Global wildlife is increasingly subject to human-induced disturbance, such as habitat loss and land-use changes. Some species are able to cope with these changes while others are not, leading to species declines and extinctions. One of the most important ways that animals cope with human disturbance is by using flexible coping strategies in new situations created by disturbance. Social grouping is one strategy that animals adapt according to the situation that they are in. The goal for any animal is to maximise the amount of food you eat while reducing your risk of death so that you can pass on your genes to the next generation. Group-living animals can reduce their risk of death by sharing the time spent looking for danger, but they also need to share food with other group members. Being flexible in the size of your group would allow you to maximise the benefits and minimise the costs of group-living given your situation. For example, animals could group together in areas with many predators to allow them to eat while sharing the time spent looking for danger and split apart in areas of low risk to reduce competition for food with other group members. Similarly, animals could group together more at times of the day or the year when their chances of encountering a predator is higher. As more and more habitat is lost or degraded, animals are forced to feed in areas that present a higher risk of encountering human predators, such a farmland. Being able to group together flexibly in risky habitats and split up in low-risk habitats may allow species to cope better with human induced-change. In this project, we aim to investigate the effect that grouping together has on where and when animals choose to feed. I will address this question using 18 female elk in one herd in Manitoba that lives in a mostly agricultural landscape. These elk wear Global Positioning System (GPS) collars that have been collecting data on their locations at regular intervals for two years. I will use a combination of tests to investigate what is driving elk to choose certain habitats and whether the distance between each animal and its closest neighbour changes in more in risky areas (i.e. agricultural land) and more risky times of day (i.e. hunting season and daytime when humans are more active). This research will give us a better understanding of how animals cope with habitat disturbance and the potential for social grouping to be used as a coping strategy. Elk populations in Manitoba are generally in decline which could have negative impacts on livelihoods of people that depend on the hunting industry. The information gained in this study will help local stakeholders to make decisions about land-use changes and hunting quotas in their area to promote the sustainable population growth of elk and support local livelihoods.

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  • Funder: UKRI Project Code: NE/V009982/1
    Funder Contribution: 8,150 GBP

    Throughout Earth's geological history, hydrothermal systems have provided habitats for the most ancient forms of life known on Earth. The warm water in these systems reacts with the local rocks and accelerates chemical reactions. As a result, different chemical compounds are released and can be exploited by microorganisms that utilize chemicals from the bedrock for metabolic energy to form a viable habitat. The geological record of Mars suggests that sulphur-rich hydrothermal systems were widespread during the Hesperian Period, around 3.8 billion years ago and possibly could have supported life as we know it on Earth. This happened shortly after the Late Heavy Bombardment (LHB), when Mars was exposed to extensive impact events. The study of the habitability of these environments is done by researching Mars analogues on Earth. The predominant heat supply of these environments on Earth comes from a magmatic source, either from a volcanic eruption or through a magmatic intrusion into the local rock. On extraterrestrial bodies such as Mars, impacts are the main heat source. The chemical difference between these hydrothermal systems are dependent on the original bedrock and the newly introduced magmatic material. The chemical potential to support microbial life and form a viable habitat between the two different environments will be studied. This will be done by studying relic hydrothermal environments, through analysing rock samples from the sulphur-rich Haughton impact crater in the high Arctic, Canada, and comparing them to magmatic intrusions from the San Raphael Swell, USA. The samples will be collected along a reaction path of unaltered rock to altered rock and analysed for their different mineralogy and chemistry. This will then be used to make a thermodynamic chemical model to understand the reaction path forming the altered rock and the past fluid composition. From the modelled data, the free energy released from the reduction-oxidation reactions will be used to evaluate the different potential of each environment to support microbial life through time and space.

    more_vert
  • Funder: UKRI Project Code: NE/T014326/1
    Funder Contribution: 9,182 GBP

    BBSRC : Laura May Murray : BB/T508330/1 Antibiotics are used to treat infections caused by bacteria. However, bacteria can become resistant to antibiotics, meaning they are still able to grow in the presence of antibiotics. For this reason, infections caused by antibiotic resistant bacteria are becoming more difficult to treat. Infections caused by antibiotic resistant bacteria are also extremely costly, for example, due to increased length of stay in hospital. Overuse and misuse of antibiotics is driving the evolution of antibiotic resistant bacteria, and it has been predicted that by 2050, someone will die every three seconds from an antibiotic resistant infection. However, there is also evidence that other antimicrobial compounds can result in the evolution of antibiotic resistance. Antimicrobials are chemicals or compounds that kill bacteria, but cannot be used for treatment of infections in humans or animals because they are too toxic. Furthermore, there is new research indicating that other chemicals, which are not used as antimicrobials (for example, human medicines) may also lead to the development of antibiotic resistance. How mixtures of antibiotics, antimicrobials and other chemicals may interact and drive the evolution of antibiotic resistance is poorly understood. Antibiotics are not just used to treat and prevent infections in humans and animals; they are also applied to agricultural soils as plant protection products (PPPs). PPPs are used globally to increase crop yields. There are many types of PPPs currently in use, such as herbicides (used to prevent growth of unwanted plants) or insecticides (used to kill pest insects). No research to date has investigated if non-antibiotic PPPs can drive evolution of antibiotic resistance. This research placement will complement work being undertaken in the BBSRC/AstraZeneca iCASE PhD studentship entitled "Investigating selection and co-selection for antimicrobial resistance by non-antibiotic drugs and plant protection products". Laboratory experiments and a variety of culture based and molecular microbiology methods will be used to determine if exposing soil bacterial communities to non-antibiotic PPPs results in increased levels of antibiotic resistance. This placement provides a unique opportunity to study exposure to PPPs in well-established experiment field plots, which are treated with PPPs annually. This will aid interpretation of laboratory experiments and provide an environmentally realistic aspect to the PhD research. The findings from this novel research may be useful for influencing regulation of PPPs, food safety policy and human health risk assessment of exposure to antibiotic resistant bacteria from environmental sources.

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  • Funder: SNSF Project Code: 194473
    Funder Contribution: 92,800
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  • Funder: UKRI Project Code: NE/T014202/1
    Funder Contribution: 9,177 GBP

    Mountain glaciers are melting at an increased rate due to climate change; this is leading to decreasing water resources for the surrounding communities, which is becoming of increasing importance in western Canada as glacier volume is expected to reduce by 70% by 2100. As a glacier melts, a lake can be formed in front of the glacier. This lake is formed due to a depression (herein called 'overdeepenings') in the landscape which has been scraped out by glacial erosion, this then fills with the generated melt water once the glacier retreats out of it and can then become dammed by deposited moraines. As these lakes continue to develop and grow, while the glacier continues to shrink, they have the potential to become hazardous, if a sudden release of water occurs, while they can become opportunities for economic benefits - such as hydroelectric dams and tourism - when the glacier disappears. Research on the formation and development of these glacial lakes has been discussed at length within the literature and is well understood. The vast majority of the research at present has focused on these glacial lakes as hazards, focusing on negative impacts such as; decreasing water resources, and the effects on downstream communities. A question which has received very little attention in the literature - and that shall be answered by this study - is that of where these glacial lakes will develop in the future as global warming causes glaciers to disappear and what these locations will look like as these, now relic, lakes dominate the environment? A limited number of studies have been trying to answer this question in to where these glacial lakes will be in the future, with a primary focus on locations of relatively important consequence, for example the Himalaya-Karakoram region. Another study, taking a more global perspective, looked into the possibility of these lakes for hydroelectric dams, which would be important contributions to national energy supplies in many countries. Both studies used estimated glacial ice thicknesses to predict where these overdeepenings have been located. Although these studies provide an understanding on the formation of future lakes, and how they will evolve, no study has tried to describe or understand what these locations will look like once these glaciers disappear and the lakes are all that remain. This study shall be working in British Columbia and Alberta in western Canada, where we shall predict where these glacial overdeepenings are under the present-day glacial ice. This shall be done by using already created estimations on global glacial ice thicknesses, and digital elevation models. These shall be used to estimate the depth and volume of lakes which maybe created in the future. We shall then compare what these future landscapes shall look like using modern day locations which are either transitioning from a glaciated to deglaciated environment with glacial lakes dominating the landscape (Cordillera Blanca, Peru), and locations that are entirely deglaciated and that the once glacial lakes, now remain (e.g. The Lake District, UK). In these localities, mapping of the moraine dams will aid in providing an understanding of where future lakes may develop. The output of this research will aid in giving an understanding on the location of future lakes within western Canada, which will assist in future decision making of the local government into water availability in an unpredictable climate.

    more_vert
  • Funder: UKRI Project Code: NE/V009958/1
    Funder Contribution: 9,854 GBP

    BBSRC : Andra-Maria Ionescu : BB/M011208/1 Back pain has long been recognised as the most significant cause of 'years lived with disability' in countries around the world, including in both the UK and Canada. Degeneration of the intervertebral disc (IVD) is the leading cause of back pain. The healthy IVD a soft, hydrated tissue located between the vertebrae in the spine which allows flexibility and protects the spine from damage during loading. The tissue is protein-rich, with relatively few cells. With degeneration the function of the cells changes, leading to a change in the tissue including a loss of hydration and disc height that ultimately causes back pain. Despite the enormity of the problem there are no long-term successful treatments and hence new areas of collaborative research are required in order to better understand the disease processes and develop novel therapies. This project will allow a new collaboration to be formed in order to investigate an important unstudied area of IVD research; whether they way in which cells handle amino acids might cause disease and whether 'rescue' of amino acid handling might have potential as a treatment for IVD degeneration and back pain. To initiate this area of research the current project will investigate amino acid handling in skeletal muscle, a tissue in which the mechanisms of amino acid handling are better understood. Amino acids are the main 'building blocks' of proteins and have an important role in the maintenance of skeletal muscle mass. Of these, the essential amino acid leucine, is particularly responsible for the activation of new muscle protein production. Therefore, it is thought that the transport of leucine into skeletal muscle may be pivotal role in the activation of muscle protein gain and thus, these could be essential for maintaining skeletal muscle mass and function with ageing and disease. Leucine transport is coordinated predominantly by two transporters, called LAT1 (L-Type Amino Acid Transporter 1) and SNAT2 (sodium-coupled neutral amino acid transporter 2); however the full importance of these transporters to skeletal muscle size and protein production is unknown. As well as leucine, other amino acids, such as arginine, glycine and methionine are also believed to activate the processes which increase muscle protein production. Therefore, if leucine transport is impaired, or leucine availability is low, these amino acids may have a compensatory effect on muscle protein production and cell size. Thus, the aim of this project will be to determine how inhibiting the leucine transporters LAT1 and SNAT2 affects leucine transport, cell size and protein production in muscle cells. Furthermore, we will then aim to understand whether high amounts of glycine, arginine and/or methionine can rescue any damaging effects of LAT1/SNAT2 inhibition. The results of this investigation will provide vital information on how leucine transport and protein production are controlled in skeletal muscle cells. It would also advise on what nutritional strategies to use to enhance muscle protein production in cases where there is a lack of leucine or reduced leucine transport. The knowledge gained from the study will also then be translated across from Canada to the UK to initiate a new area of collaborative international research into study of amino acid handling in the IVD which has the potential ultimately to revolutionise treatment of back pain and thereby alleviate the associated impact of the disease to both countries.

    more_vert
  • Funder: WT Project Code: 215695
    Funder Contribution: 835,847 GBP

    We are proposing a new and innovative precision approach to the identification of severe infections and sepsis in children. This data-driven approach to diagnosis will overcome many of the limitations of current expert opinion-based triage guidelines. Smart technology has the potential to overcome the barrier of limited clinical expertise in the identification of the child at risk. This mobile health platform, with sensors and data-driven applications, will provide real-time individualised risk prediction to facilitate timely and effective targeted treatment at first contact, regardless of location. This low-cost technology will provide rapid triage in remote areas globally where specialists are not regularly available. We will trigger rapid, highly effective and low-cost interventions such as antibiotics, fluid, oxygen therapy and other special investigations to children determined to be most at risk of sepsis, based on data-driven prediction. Thus, these innovations will improve timely access to life-saving treatments for children in the poorest countries where deaths from infection and sepsis are common. Children in poor families or in populations marginalized by health and social inequities are especially vulnerable to infections. In these children, infection is a major contributor to disability and years of life lost and has a great economic and social cost. Sepsis is the leading cause of death and disability in children, every hour of delay in treatment is associated with greater organ damage and ultimately death. The challenges, especially in poor countries, are the delays in diagnosis and the inability to identify children in urgent need of treatment. To circumvent these challenges, we propose the implementation and evaluation of a trigger tool that will reduce the time to diagnosis and prompt the timely initiation of life-saving treatment. The key innovations are 1) a data-driven approach to rapid diagnosis of sepsis severity and 2) a low-cost digital tagging system to track the time to treatment. The tool will require minimal cost, clinical expertise and training or time to use. The tool will identify high risk children and reduce time to treatment. Our mobile platform (mobile device and dashboard) will create a low-cost, highly scalable solution for children with sepsis.

    more_vert
54 Projects
  • Funder: UKRI Project Code: EP/V043811/1
    Funder Contribution: 497,214 GBP

    Coronaviruses are transmitted from an infectious individual through large respiratory droplets generated by coughing, sneezing or speaking. These infectious droplets are then transmitted to the mucosal surfaces of a recipient through inhalation of the aerosol or by contact with contaminated fomites such as surfaces or other objects. In healthcare settings, personal protective equipment (PPE) plays a crucial role in interrupting the transmission of highly communicable diseases such as COVID19 from patients to healthcare workers (HCWs). However, research has shown that PPE can also act as a fomite during the donning and doffing process as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can survive on these surfaces for up to three days. This creates a need for more effective PPE materials that can provide antiviral protection. In this proposal we aim to develop a dual action antiviral/antifouling coating to lower the risk of transmission of the SARS-CoV-2 to HCWs from COVID19 patients. This project will deliver antiviral/antifouling coatings that can be readily applied to PPE surfaces such as faceshields that are likely to encounter a high level of viral load and would be of great benefit to the health of clinical staff. Furthermore, this project has embedded into its planning a rapid pathway for optimisation, translation, and upscaling of manufacture to deliver a low-cost technology within a short timescale.

    visibility35
    visibilityviews35
    downloaddownloads21
    Powered by Usage counts
    more_vert
  • Funder: UKRI Project Code: NE/V010131/1
    Funder Contribution: 7,776 GBP

    NERC: Jennifer Watts: NE/S007504/1

    more_vert
  • Funder: NSF Project Code: 1907243
    Funder Contribution: 138,000 USD
    more_vert
  • Funder: UKRI Project Code: NE/V010034/1
    Funder Contribution: 9,100 GBP

    NERC : Zoe Melvin : NE/L002604/1 Global wildlife is increasingly subject to human-induced disturbance, such as habitat loss and land-use changes. Some species are able to cope with these changes while others are not, leading to species declines and extinctions. One of the most important ways that animals cope with human disturbance is by using flexible coping strategies in new situations created by disturbance. Social grouping is one strategy that animals adapt according to the situation that they are in. The goal for any animal is to maximise the amount of food you eat while reducing your risk of death so that you can pass on your genes to the next generation. Group-living animals can reduce their risk of death by sharing the time spent looking for danger, but they also need to share food with other group members. Being flexible in the size of your group would allow you to maximise the benefits and minimise the costs of group-living given your situation. For example, animals could group together in areas with many predators to allow them to eat while sharing the time spent looking for danger and split apart in areas of low risk to reduce competition for food with other group members. Similarly, animals could group together more at times of the day or the year when their chances of encountering a predator is higher. As more and more habitat is lost or degraded, animals are forced to feed in areas that present a higher risk of encountering human predators, such a farmland. Being able to group together flexibly in risky habitats and split up in low-risk habitats may allow species to cope better with human induced-change. In this project, we aim to investigate the effect that grouping together has on where and when animals choose to feed. I will address this question using 18 female elk in one herd in Manitoba that lives in a mostly agricultural landscape. These elk wear Global Positioning System (GPS) collars that have been collecting data on their locations at regular intervals for two years. I will use a combination of tests to investigate what is driving elk to choose certain habitats and whether the distance between each animal and its closest neighbour changes in more in risky areas (i.e. agricultural land) and more risky times of day (i.e. hunting season and daytime when humans are more active). This research will give us a better understanding of how animals cope with habitat disturbance and the potential for social grouping to be used as a coping strategy. Elk populations in Manitoba are generally in decline which could have negative impacts on livelihoods of people that depend on the hunting industry. The information gained in this study will help local stakeholders to make decisions about land-use changes and hunting quotas in their area to promote the sustainable population growth of elk and support local livelihoods.

    more_vert
  • Funder: UKRI Project Code: NE/V009982/1
    Funder Contribution: 8,150 GBP

    Throughout Earth's geological history, hydrothermal systems have provided habitats for the most ancient forms of life known on Earth. The warm water in these systems reacts with the local rocks and accelerates chemical reactions. As a result, different chemical compounds are released and can be exploited by microorganisms that utilize chemicals from the bedrock for metabolic energy to form a viable habitat. The geological record of Mars suggests that sulphur-rich hydrothermal systems were widespread during the Hesperian Period, around 3.8 billion years ago and possibly could have supported life as we know it on Earth. This happened shortly after the Late Heavy Bombardment (LHB), when Mars was exposed to extensive impact events. The study of the habitability of these environments is done by researching Mars analogues on Earth. The predominant heat supply of these environments on Earth comes from a magmatic source, either from a volcanic eruption or through a magmatic intrusion into the local rock. On extraterrestrial bodies such as Mars, impacts are the main heat source. The chemical difference between these hydrothermal systems are dependent on the original bedrock and the newly introduced magmatic material. The chemical potential to support microbial life and form a viable habitat between the two different environments will be studied. This will be done by studying relic hydrothermal environments, through analysing rock samples from the sulphur-rich Haughton impact crater in the high Arctic, Canada, and comparing them to magmatic intrusions from the San Raphael Swell, USA. The samples will be collected along a reaction path of unaltered rock to altered rock and analysed for their different mineralogy and chemistry. This will then be used to make a thermodynamic chemical model to understand the reaction path forming the altered rock and the past fluid composition. From the modelled data, the free energy released from the reduction-oxidation reactions will be used to evaluate the different potential of each environment to support microbial life through time and space.

    more_vert
  • Funder: UKRI Project Code: NE/T014326/1
    Funder Contribution: 9,182 GBP

    BBSRC : Laura May Murray : BB/T508330/1 Antibiotics are used to treat infections caused by bacteria. However, bacteria can become resistant to antibiotics, meaning they are still able to grow in the presence of antibiotics. For this reason, infections caused by antibiotic resistant bacteria are becoming more difficult to treat. Infections caused by antibiotic resistant bacteria are also extremely costly, for example, due to increased length of stay in hospital. Overuse and misuse of antibiotics is driving the evolution of antibiotic resistant bacteria, and it has been predicted that by 2050, someone will die every three seconds from an antibiotic resistant infection. However, there is also evidence that other antimicrobial compounds can result in the evolution of antibiotic resistance. Antimicrobials are chemicals or compounds that kill bacteria, but cannot be used for treatment of infections in humans or animals because they are too toxic. Furthermore, there is new research indicating that other chemicals, which are not used as antimicrobials (for example, human medicines) may also lead to the development of antibiotic resistance. How mixtures of antibiotics, antimicrobials and other chemicals may interact and drive the evolution of antibiotic resistance is poorly understood. Antibiotics are not just used to treat and prevent infections in humans and animals; they are also applied to agricultural soils as plant protection products (PPPs). PPPs are used globally to increase crop yields. There are many types of PPPs currently in use, such as herbicides (used to prevent growth of unwanted plants) or insecticides (used to kill pest insects). No research to date has investigated if non-antibiotic PPPs can drive evolution of antibiotic resistance. This research placement will complement work being undertaken in the BBSRC/AstraZeneca iCASE PhD studentship entitled "Investigating selection and co-selection for antimicrobial resistance by non-antibiotic drugs and plant protection products". Laboratory experiments and a variety of culture based and molecular microbiology methods will be used to determine if exposing soil bacterial communities to non-antibiotic PPPs results in increased levels of antibiotic resistance. This placement provides a unique opportunity to study exposure to PPPs in well-established experiment field plots, which are treated with PPPs annually. This will aid interpretation of laboratory experiments and provide an environmentally realistic aspect to the PhD research. The findings from this novel research may be useful for influencing regulation of PPPs, food safety policy and human health risk assessment of exposure to antibiotic resistant bacteria from environmental sources.

    more_vert
  • Funder: SNSF Project Code: 194473
    Funder Contribution: 92,800
    more_vert
  • Funder: UKRI Project Code: NE/T014202/1
    Funder Contribution: 9,177 GBP

    Mountain glaciers are melting at an increased rate due to climate change; this is leading to decreasing water resources for the surrounding communities, which is becoming of increasing importance in western Canada as glacier volume is expected to reduce by 70% by 2100. As a glacier melts, a lake can be formed in front of the glacier. This lake is formed due to a depression (herein called 'overdeepenings') in the landscape which has been scraped out by glacial erosion, this then fills with the generated melt water once the glacier retreats out of it and can then become dammed by deposited moraines. As these lakes continue to develop and grow, while the glacier continues to shrink, they have the potential to become hazardous, if a sudden release of water occurs, while they can become opportunities for economic benefits - such as hydroelectric dams and tourism - when the glacier disappears. Research on the formation and development of these glacial lakes has been discussed at length within the literature and is well understood. The vast majority of the research at present has focused on these glacial lakes as hazards, focusing on negative impacts such as; decreasing water resources, and the effects on downstream communities. A question which has received very little attention in the literature - and that shall be answered by this study - is that of where these glacial lakes will develop in the future as global warming causes glaciers to disappear and what these locations will look like as these, now relic, lakes dominate the environment? A limited number of studies have been trying to answer this question in to where these glacial lakes will be in the future, with a primary focus on locations of relatively important consequence, for example the Himalaya-Karakoram region. Another study, taking a more global perspective, looked into the possibility of these lakes for hydroelectric dams, which would be important contributions to national energy supplies in many countries. Both studies used estimated glacial ice thicknesses to predict where these overdeepenings have been located. Although these studies provide an understanding on the formation of future lakes, and how they will evolve, no study has tried to describe or understand what these locations will look like once these glaciers disappear and the lakes are all that remain. This study shall be working in British Columbia and Alberta in western Canada, where we shall predict where these glacial overdeepenings are under the present-day glacial ice. This shall be done by using already created estimations on global glacial ice thicknesses, and digital elevation models. These shall be used to estimate the depth and volume of lakes which maybe created in the future. We shall then compare what these future landscapes shall look like using modern day locations which are either transitioning from a glaciated to deglaciated environment with glacial lakes dominating the landscape (Cordillera Blanca, Peru), and locations that are entirely deglaciated and that the once glacial lakes, now remain (e.g. The Lake District, UK). In these localities, mapping of the moraine dams will aid in providing an understanding of where future lakes may develop. The output of this research will aid in giving an understanding on the location of future lakes within western Canada, which will assist in future decision making of the local government into water availability in an unpredictable climate.

    more_vert
  • Funder: UKRI Project Code: NE/V009958/1
    Funder Contribution: 9,854 GBP

    BBSRC : Andra-Maria Ionescu : BB/M011208/1 Back pain has long been recognised as the most significant cause of 'years lived with disability' in countries around the world, including in both the UK and Canada. Degeneration of the intervertebral disc (IVD) is the leading cause of back pain. The healthy IVD a soft, hydrated tissue located between the vertebrae in the spine which allows flexibility and protects the spine from damage during loading. The tissue is protein-rich, with relatively few cells. With degeneration the function of the cells changes, leading to a change in the tissue including a loss of hydration and disc height that ultimately causes back pain. Despite the enormity of the problem there are no long-term successful treatments and hence new areas of collaborative research are required in order to better understand the disease processes and develop novel therapies. This project will allow a new collaboration to be formed in order to investigate an important unstudied area of IVD research; whether they way in which cells handle amino acids might cause disease and whether 'rescue' of amino acid handling might have potential as a treatment for IVD degeneration and back pain. To initiate this area of research the current project will investigate amino acid handling in skeletal muscle, a tissue in which the mechanisms of amino acid handling are better understood. Amino acids are the main 'building blocks' of proteins and have an important role in the maintenance of skeletal muscle mass. Of these, the essential amino acid leucine, is particularly responsible for the activation of new muscle protein production. Therefore, it is thought that the transport of leucine into skeletal muscle may be pivotal role in the activation of muscle protein gain and thus, these could be essential for maintaining skeletal muscle mass and function with ageing and disease. Leucine transport is coordinated predominantly by two transporters, called LAT1 (L-Type Amino Acid Transporter 1) and SNAT2 (sodium-coupled neutral amino acid transporter 2); however the full importance of these transporters to skeletal muscle size and protein production is unknown. As well as leucine, other amino acids, such as arginine, glycine and methionine are also believed to activate the processes which increase muscle protein production. Therefore, if leucine transport is impaired, or leucine availability is low, these amino acids may have a compensatory effect on muscle protein production and cell size. Thus, the aim of this project will be to determine how inhibiting the leucine transporters LAT1 and SNAT2 affects leucine transport, cell size and protein production in muscle cells. Furthermore, we will then aim to understand whether high amounts of glycine, arginine and/or methionine can rescue any damaging effects of LAT1/SNAT2 inhibition. The results of this investigation will provide vital information on how leucine transport and protein production are controlled in skeletal muscle cells. It would also advise on what nutritional strategies to use to enhance muscle protein production in cases where there is a lack of leucine or reduced leucine transport. The knowledge gained from the study will also then be translated across from Canada to the UK to initiate a new area of collaborative international research into study of amino acid handling in the IVD which has the potential ultimately to revolutionise treatment of back pain and thereby alleviate the associated impact of the disease to both countries.

    more_vert
  • Funder: WT Project Code: 215695
    Funder Contribution: 835,847 GBP

    We are proposing a new and innovative precision approach to the identification of severe infections and sepsis in children. This data-driven approach to diagnosis will overcome many of the limitations of current expert opinion-based triage guidelines. Smart technology has the potential to overcome the barrier of limited clinical expertise in the identification of the child at risk. This mobile health platform, with sensors and data-driven applications, will provide real-time individualised risk prediction to facilitate timely and effective targeted treatment at first contact, regardless of location. This low-cost technology will provide rapid triage in remote areas globally where specialists are not regularly available. We will trigger rapid, highly effective and low-cost interventions such as antibiotics, fluid, oxygen therapy and other special investigations to children determined to be most at risk of sepsis, based on data-driven prediction. Thus, these innovations will improve timely access to life-saving treatments for children in the poorest countries where deaths from infection and sepsis are common. Children in poor families or in populations marginalized by health and social inequities are especially vulnerable to infections. In these children, infection is a major contributor to disability and years of life lost and has a great economic and social cost. Sepsis is the leading cause of death and disability in children, every hour of delay in treatment is associated with greater organ damage and ultimately death. The challenges, especially in poor countries, are the delays in diagnosis and the inability to identify children in urgent need of treatment. To circumvent these challenges, we propose the implementation and evaluation of a trigger tool that will reduce the time to diagnosis and prompt the timely initiation of life-saving treatment. The key innovations are 1) a data-driven approach to rapid diagnosis of sepsis severity and 2) a low-cost digital tagging system to track the time to treatment. The tool will require minimal cost, clinical expertise and training or time to use. The tool will identify high risk children and reduce time to treatment. Our mobile platform (mobile device and dashboard) will create a low-cost, highly scalable solution for children with sepsis.

    more_vert