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  • UK Research and Innovation
  • 2008
  • 2012

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  • Funder: UKRI Project Code: G0601295
    Funder Contribution: 1,222,890 GBP

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

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  • Funder: UKRI Project Code: BBS/E/C/00004947
    Funder Contribution: 569,194 GBP

    Most insects respond to each other and to other organisms within their environment. Many of these interactions are mediated by volatile chemicals which act as signals without having a direct physiological effect. Such semiochemicals may elicit a specific response in the same species, for example the sex, alarm and aggregation pheromones produced by many insect species. Other signal chemicals are produced by one species and cause a response in another (allelochemicals), for example chemicals from host organisms which attract insect pests and chemicals from non-hosts which are repellent. Such allelochemicals are responsible for the location of hosts by both crop pests and insect vectors of animal/human diseases. We are studying the genes and proteins involved in the interaction between insects and semiochemicals. This involves cloning and characterising genes encoding insect odorant-binding proteins (OBPs), chemosensory proteins (CSPs) and odorant receptors (ORs). The OBPs (and possibly CSPs) are involved in the initial binding of signal molecules within the antennae and transfer of the odours to the ORs and there is good evidence that these proteins confer some of the specificity of the insects' response to the signals. Using bioinformatic techniques we have identified genes encoding OBPs and CSPs from fruit flies, mosquitoes, moths and aphids and are determining which are expressed in antennae (using quantitative RT-PCR) and could therefore be involved in olfaction. The candidate genes are then cloned and expressed into recombinant proteins and these can be purified for ligand-binding studies. A range of techniques to identify which semiochemicals interact with which OBP are being developed and we are also developing new ways to study ligand/OBP/OR interactions. The functionality of the genes identified can be determined by gene silencing techniques combined with electrophysiological/behavioural assays.

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  • Funder: UKRI Project Code: EP/G010420/1
    Funder Contribution: 155,137 GBP

    In England, approximately 110,000 patients suffer a stroke each year, and at least 300,000 people live with moderate to severe disabilities as a result. The direct cost to the NHS of stroke is estimated to be 2.8 billion per year, with additional costs of informal care around 2.4 billion. Stroke accounts for about 11% of deaths, and around half of the survivors depend on others for everyday activities. Further research to reduce the incidence and long-term consequences of strokes on patients' lives is clearly called for. The brain requires a constant supply of blood to ensure that sufficient oxygen and nutrients are always available, and waste products produced by active cells are rapidly removed. A complex control system that dilates and constricts small arteries in the brain achieves this efficiently in healthy humans. This system, which is still poorly understood, responds to changing blood pressure (e.g. during exercise or when standing up), changes in breathing pattern, and variations in brain activity (e.g. waking / sleeping or responding to sensory stimuli). If the control system fails (e.g. following trauma or in premature babies), the subject may suffer from insufficient or excessive blood flow, either of which can lead to temporary or permanent brain damage, provoking strokes or aggravating their consequences. It is important to detect impairment of the control system early, in order to ensure appropriate care for the patient, such as keeping their blood pressure constant to avoid further brain damage. However, it is very difficult to measure whether a patient's blood flow is adequately regulated. Techniques that are currently used may require the patients' blood pressure to be changed quite considerably, but this cannot be done safely in vulnerable subjects. Procedures used are often uncomfortable and results not very reliable.We are proposing new experimental methods that are less aggressive and therefore might in the future be used in a wider group of patients. These methods use a variety of repeated small random changes in blood pressure (and also inhaled carbon dioxide concentrations), rather than larger swings. Extending previous work carried out by our teams in Southampton, Leicester and Norwich, we will simultaneously record blood pressure (using non-invasive methods) and blood flow in two arteries in the brain (using Doppler ultrasound applied on the outside of the head over the temples), together with CO2 in breathed air. From the small fluctuations in the prolonged recordings of these signals, we will estimate the characteristics of the system controlling blood flow, and in particular whether it is operating adequately, or is impaired. We will only carry out the experiments on healthy adult volunteers, and will provoke temporary impairment of the control system, by inhalation of air with increased levels of CO2, a procedure that is quite safe in the controlled laboratory conditions.In addition to developing new experimental methods, we will also develop and apply novel mathematical and computational techniques for signal-data analysis, which we believe will be more effective for the data we are investigating. Advanced statistical methods will be used to analyse results, and distinguish the known random variations between subjects (and also in repeated test in the same subject), from significant changes. In this joint project, we will be able to compare a number of different experimental methods and data processing techniques, in order to identify the ones with the best performance.In summary, the aims of the project are to investigate and develop new experimental protocols and data analysis methods, in order to provide new techniques that can be used to assess patients' brain blood flow control. We also expect this work to help understand better, how the control system works in healthy human subjects. As outcome we expect to recommend one or more new methods for future use in hospitals.

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  • Funder: UKRI Project Code: NE/F004753/1
    Funder Contribution: 270,485 GBP

    Rivers have (rather controversially) been described as 'simply outcrops of groundwater'. Many of the rivers in the UK are supplied mainly from groundwater sources, especially during the summer months when rainfall is characteristically low. The hyporheic zone is a critical interface between surface and subsurface waters in groundwater catchments. Here, the mixing of groundwater and surface water and the resulting biological and chemical reactions, may exert a lot of control on the water quality of the river and also its ecology: so much so that the hyporheic zone has been ascribed pollutant attenuating properties by some. Groundwater abstraction, effluent disposal and diffuse nutrient pressures - especially nitrogen - may all compromise the capacity of the hyporheic zone to influence the water quality of a river. Although quite a few researchers have recognised that the hyporheic zone has some special control on the river habitat, most have looked at it only from the perspective of the relationship between river water and the upper few centimetres of the sediments of the riverbed. They have ignored the fact that as well as downward flux from the river into the sediments of the riverbed there will also be upward flows from groundwater through the hyporheic zone and into the river. We are especially interested in what happens to the chemistry of groundwater as it moves through the hyporheic zone. We will look in detail at the relationship between different nitrogen species, such as nitrate and ammonium and chemical reactions known collectively as 'redox' or reduction-oxidation reactions. Redox reactions use electron acceptors other than oxygen for organic carbon oxidation as the amount of oxygen in the riverbed sediments is exhausted. These reactions and their relationship with nitrogen are important because the hyporheic zone has been proposed as a zone in which nitrogen attenuation occurs. This has led to the proposition that the movement of groundwater through this zone will reduce the concentration of nitrogen reaching the river water. In this project, we will investigate further the claim that the hyporheic zone can attenuate groundwater contaminants such as nitrate. We want to look much more carefully at the pattern of flow from groundwater through the hyporheic zone. We propose that groundwater flux is influenced by the permeability of the river bed and this is in turn influenced by the physical structure and topography of the riverbed. We believe that where the permeability of the riverbed is high and flux from groundwater towards the river is high, we will find different patterns of biogeochemical activity in the hyporheic zone compared to where the permeability is low. We like to think of the riverbed rather like a cheese grater with fast and slow flow pathways corresponding to 'holes' in the riverbed. We expect these holes to be quite dynamic as winter storms change the superficial topography of the riverbed sediments and rearrange the patterns of pool-riffle and fast-slow flow features in the underlying sediments of a river. The reason why these flow pathways are important is they may allow 'hotspots' of biogeochemical activity within the hyporheic zone that could be important controls on the ecology of groundwater-fed rivers because they either release or transform nitrogen through processes such as nitrification or denitrification. The latter converts nitrate, which can damage the ecology of a river where it is present at high concentrations, into nitrogen gas, which is harmless. If we are able to show clearly how important the hyporheic zone is in influencing the water quality in rivers that are groundwater-fed, we will be able to provide evidence that can be used to protect this zone, and can also be used in helping the UK meet the requirements of critical European legislation such as the Water Framework Directive.

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  • Funder: UKRI Project Code: G0800250
    Funder Contribution: 450,000 GBP

    In vitro fertilisation (IVF) and associated technologies remain relatively inefficient and costly and the problems worsen with increasing maternal age. One of the main reasons for these low success rates is poor oocyte (egg) quality, as we know very little about the biology of mammalian egg development and the factor(s) which make eggs fertile. This issue is exacerbated by the limited available of human eggs for research. In order to improve the success of assisted conception treatments we need to maximise the number of good quality eggs we collect from a woman?s ovaries but we must be careful that egg quality does not suffer at the expense of egg quantity. The current momentum in assisted conception is therefore to produce a small number of good eggs from each patient and so maximise their change of a pregnancy. However, this goal can only be achieved if we can identify the best eggs for IVF and use this information to improve patient treatments and so maximise egg quality. The objective of this project is therefore to measure egg quality in healthy women and to use this information to establish a cellular and molecular signature of egg health from patients with defined causes of infertility. The project aims to: (1) define and link biochemical and metabolic markers of egg quality; (2) investigate a number of key genes which may contribute to egg health; and (3) measure the impact of different assisted reproduction treatment regimes on egg quality. Some aspects of the research will be conducted using cow eggs as these tissues are a good model for human egg development; other components of the project will be conducted using human eggs which have been donated for research by infertility patients. We have already developed and validated the molecular biology methods and assays of egg protein turnover and energy metabolism which will be utilised on this project to measure egg quality. The data generated by the proposed studies will significantly advance our understanding of human egg biology and will ultimately help reduce the cost and improve the success rates of assisted conception treatments.

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  • Funder: UKRI Project Code: EP/F007426/1
    Funder Contribution: 3,148,360 GBP

    The first phase of the SUE Programme has focused necessarily on the present, assessing current solutions and their application in the near future, thus providing a strong empirical base on which to build. There now exist both the need and a sufficient body of work to extrapolate the findings to establish and test alternative urban futures: to create a variety of scenarios, building on prior and new work, and predicated on different fundamental assumptions and priorities; to assess those scenarios in terms of design, engineering implementation and measurement of performance; to refine them, in terms of mitigation and adaptation measures, incorporating novel solutions; and ultimately to provide alternative solutions with an associated evidence base and strategies for their implementation. This bid seeks to integrate the outputs of three current SUE consortia (Birmingham Eastside, VivaCity 2020 and WaND) and complementary research on the use of trees to mitigate the effects of atmospheric pollution. The team will work across disciplines to envision and establish alternative futures (using extensive literature on this subject and prior WaND consortium work) and construct scenarios that might flow from each alternative future. The various work packages will then focus on testing specific dimensions of each alternative future vis a vis their design, implementation and performance in the context of case history sites. Each project will engage an expert panel of influential stakeholders who will meet six-monthly to test and help shape new ideas, the chairs of each of the expert panels forming the higher level project steering committee. Panel consultation will be followed by interviews of stakeholders on motivations and the decision-making process, and specific empirical research and modelling. The following high level questions will be addressed via this process: - How does the ab initio conceptualization of sustainability influence design outcomes (e.g. form, density)? How would outcomes change if urban renewal were predicated on either environmental or social or economic overriding drivers? - How does development impact on its environs, and vice versa (e.g. is a 'sustainable' site good for the city / region / country and, if so, in what ways?) and is there an optimum development size to yield optimally sustainable outcomes? - Push versus pull to achieve sustainable outcomes. Much of what is done is thought good (for individuals, society, the environment), what might be wanted (push). Thus decisions are made and people must decide whether or not to take ownership. Might more sustainable outcomes follow if those who must take ownership dictate what is created (pull)? Birmingham Eastside will be used both to develop sustainability ideas and to test them on sites at various stages of planning and development (the research team has unparalleled access via its partnerships with key stakeholders involved in Eastside). Lancaster (with Morecambe, population 96k) and Worcester (94k) will be used to test the outcomes at the scale of smaller urban areas (e.g. market towns) but no attempt will be made to build comprehensive databases as at Eastside. Several other UK and international urban areas (including Sao Paulo, Singapore and an urban area in India) will be used to test a sub-set of the project's findings to assess the transferability of the scenarios to a variety of contexts and thus their general applicability.

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  • Funder: UKRI Project Code: NE/F002971/1
    Funder Contribution: 326,620 GBP

    The ocean plays a central role in the global carbon cycle. Uptake of carbon dioxide by the oceans has reduced the increase in atmospheric carbon dioxide that has arisen from fossil fuel burning and deforestation. It has long been know that the ocean biota play a major role in sequestering carbon dioxide on very long time scales (>1000 years). Recent evidence also suggests that the ocean biota play an important role on shorter time scales (10-100 years) as well. The balance between phytoplankton photosynthesis and community respiration determines the ability of the oceans to take up carbon dioxide. Nitrogen is generally considered to be the nutrient that limits phytoplankton photosynthesis. But what limits the amount of N in the ocean? Unlike most phytoplankton, which are N-limited, nitrogen fixing cyanobacteria have an unlimited supply of N. This is the N2 gas that is dissolved in seawater. Nitrogen-fixing cyanobacteria play a significant role in ocean nutrient and biogeochemical cycles as they are a major source of N, providing N for up to 50% of primary productivity in the most nutrient impoverished regions of the ocean. Nitrogen fixation is a key process that modulates the ability of the oceans to sequester carbon dioxide on time scales of 10 to 10,000 years. Limitation of nitrogen fixation results in lowered N availability for other primary producers reducing the potential of oligotrophic oceans to sequester carbon. This brings us to the issue of 'What limits the amount of nitrogen fixation in the ocean?' Amongst the environmental factors that may limit nitrogen fixation are temperature, light, carbon dioxide concentration and P- or Fe-limitation. It is argued that whereas N is the proximate limiting nutrient for phytoplankton photosynthesis in the sea, the ultimate limiting nutrient is either P (or Fe) because this nutrient limits the amount of nitrogen fixation. This proposal will examine the effects of light, carbon dioxide, P-limitation and Fe-limitation on photosynthetic properties and nitrogen fixation of nitrogen-fixing cyanobacteria. Research will be conducted under defined culture conditions in two species. One of these species, Trichodesmium, is documented to be of global significance. In addition, nitrogen fixation by unicellular cyanobacteria has recently been recognized to be significant. Therefore, the second species is one of these unicellular nitrogen fixers, Crocosphaera. The outcomes of this study will provide new insights into the mechanisms by which phosphorous and iron limit photosynthesis and nitrogen fixation in cyanobacteria. It will also provide new insights into the interaction with environmental factors such as light and carbon dioxide. This research will ultimately assist with several aspects of oceanographic studies on nutrient cycling and modeling the future importance of the oceans as C sinks.

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  • Funder: UKRI Project Code: EP/F064802/1
    Funder Contribution: 1,312,770 GBP

    The challengeHuman error and systemic failure lead to unnecessary harm and suffering for patients, including permanent impairment and loss of life. Research indicates that in up to 10% of all hospitals admissions some kind of adverse incident occurs, more than half of which are believed to be avoidable. The effect on staff and the 2billion+ consequential costs further increase the need to improve all aspects of patient safety. A significant contributory factor is that healthcare processes have undergone many revisions in recent years, while the design of much non-surgical equipment remains largely unchanged. Modern healthcare involves a combination of processes and procedures supported by a broad range of equipment and products that have to co-exist within the 'patient cubicle' or ward treatment space. Few of these have been designed to ensure safe integration within the context of use, be it ward, theatre, or community, nor is this a purchasing requirement within NHS Trusts. In short, current treatments are not properly and effectively supported by available equipment. Research aimsThe outcomes of this research will be both patient and system aware. The aims are to enhance patient safety in hospital by designing out medical error, to ensure that medical products and equipment are fit for purpose, and to contain risks associated with the introduction of new designs into a system of great complexity. The Chief Medical Officer recognises the potential of a design-led approach to patient safety and wishes to see it adopted more widely across the NHS. To design out medical error it is necessary to: (i) understand healthcare process demands with regard to diagnostic, monitoring and treatment routines, in particular in terms of the consistency and usability of interfaces and other features, and in light of the progressive introduction of 'smart' products and equipment; (ii) translate that understanding into a knowledge base for the design of medical products and equipment that support safer and more effective healthcare processes; (iii) establish a best-practice, evidence-based approach to the design, equivalent to that underpinning the development of treatments, procedures and medication regimes in modern medicine. Research approachWe will use both global and candidate approaches in the project. The global approach will follow a systematic methodology to capture the broader system of healthcare process and ensure there are no gaps in our understanding of the patients/system interactions. In addition, we identified from our clinical observations and design perspective, three candidates that require detailed attention in the project: (i) the communication process in the ward; (ii) the patient local environment personal cubicle and (iii) the ward clinical activity.In order to address the broader challenge of equipment and products in use on the hospital ward, a Consultant Surgeon and Clinical Reader at Imperial, Mr George Hanna, who has research interest in ergonomics, instrument design and surgical safety will lead the clinical side of the programme. Professor Charles Vincent will lead on healthcare process and patient safety aspects, and PhDs will be attached to each of these strands to build up a cadre of young researchers in the field.DeliverablesThe project will have the following deliverables (i) a thorough map of healthcare processes both on a ward and within the broader context of the patient journey (ii) comprehensive knowledge of the design requirements for ward equipment; (iii) design proposals for a ward communication system, (iv) design proposals for a ward treatment space or 'patient cubicle' and (v) guidelines for safe ward activities and staffing levels.

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  • Funder: UKRI Project Code: BB/F018193/1
    Funder Contribution: 72,540 GBP

    Fresh produce such as salad crops are generally grown outdoors in soil and irrigated by surface water abstractions. As a consequence crops are exposed to the risk of contamination by a range of pathogenic bacteria. Indeed, numerous outbreaks of gastrointestinal disease have been identified as being caused by ingestion of fresh produce so contaminated. Leading UK salad producers such as Vitacress go to considerable lengths to ensure pathogen-free soil. For example, no animal grazing or manures for 5 years pre cropping; no compost with animal manure for 2 years pre-cropping unless audited and tested batch by batch to prove free of Salmonella and low counts of E. coli etc. Consequently, there are many codes in place to ensure pathogen-free soil. However, it is recognised that outdoor crops will get contaminated, for example by animal intruders, birds, and of course poor quality irrigation water that has been contaminated up stream of abstraction. These vectors may potentially carry zoonotic pathogens such as Salmonella, E. coli O157 and Campylobacter. The risk of infection is much greater than for the majority of other food types because these are cooked or preserved by pickling, fermentation etc. At present, the most important means of sanitising fresh produce is by washing with chlorine post-harvest. However, there are safety and consumer preference concerns connected to the use of chlorine. Alternative technologies are beginning to be advocated, driven by the desire of large multiple retailers to get away from reliance on chlorine. These include the use of ozonation augmented with UV irradiation, hydrogen peroxide and citrox. There is now an urgent need to utilise our knowledge of microbial physiology and genomics to develop new procedures to assess the ability of these newer sanitisation technologies to decontaminate important foodborne pathogens on the fresh produce surface. Indeed, do motile pathogens migrate into stomata and below the leaf outer surface, making them more inaccessible to the currently used sanitisers? Do they interact, structurally or physiologically, with the microflora that is already present on the leaf in ways that might interfere with their removal or sanitation? An Industrial case studentship nearing completion has shown that for motile Salmonella, both of these mechanisms occur, and that these attached pathogens are highly resistant to disinfection and some become sub-lethally stressed by the treatments, making them difficult to recover using conventional culture techniques due to their viable but nonculturable (VNC) state. This VNC state may help explain why agents causing major outbreaks of foodborne disease go undetected at source. New microscopy and resuscitation techniques have been developed to assess the microbial quality of harvested salads, indicating the limitations of the current codes and growing practices in excluding natural biofilms and pathogens from the production chain, as well confirming that existing and novel sanitisation technologies are ineffective in removing any potential pathogen risk. Recent work has indicated that nitric oxide producing systems may have the potential to release biofilms and zoonotic pathogens from the salad leaf phylloplane, probably through interplay with their di-cyclic GMP regulatory pathways for attachment/detachment, and also now render them susceptible to conventional disinfection strategies. These observations will be confirmed for the agents of major salad borne outbreaks of disease, E. coli O157 and Salmonella enterica, and the mechanisms of the nitric oxide response at the phylloplane elucidated. This knowledge will be transferred into the salad processing factory environment to ensure the safe supply of salads to the public. The combination of microbiology, molecular biology and engineering expertise proposed in the project should lead to reduced incidence of disease transmission due to consumption of contaminated fresh produce.

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  • Funder: UKRI Project Code: EP/F040857/1
    Funder Contribution: 1,251,550 GBP

    Technologies associated with looking at the microworld are extremely mature, and include a wide variety of microscopies. By contrast little work has been done to extend our sense of hearing into the micro-world. The purpose of this grant is to develop a basic technology for listening to the micro world, in as sense a micro ear.Just like our own ears, most sound detectors respond to changes in pressure, creating small acoustic forces and corresponding displacement of a sensor. One extremely sensitive way of measuring force is to compare it against the momentum of a light beam. Tightly focused laser beams are now routinely used to form optical tweezers, which can trap micron-sized beads, overcoming both the thermal and gravitation forces. These tweezers systems are typically built around a microscope and manipulate samples suspended in a fluid medium / such that the technology is highly compatible with biological systems. Using a microscope to observe the bead position allows the measurement of piconewton forces and the corresponding displacement of a few nanometres. The subtle movements of these optically trapped beads will form the basis of our micro-ear. We plan to develop, demonstrate and test a number of different micro-ear approaches. All imaging systems based upon focusing are restricted to scales of a wavelength or so. Even in water, acoustic wavelengths are 100s mm, making the concept of focussing irrelevant to microscopic systems. However, as evident by most wind instruments or antique hearing aids, sub wavelength horns still work. In this proposal we plan to use microfabrication techniques to produce structures that channel the fluid flow from the emitting object to the sensor bead, providing a method of guiding the pressure wave, and if necessary amplifying it (e.g. in a flared channel). We will use the optically trapped beads as sensors to measure these forces (as described above). However, it is important to consider that, at the microscale, the movements of the beads due to an acoustic response may be masked by Brownian motion / and hence distinguishing the real signal from this thermal background will be a major challenge challenge.The key to overcoming the Brownian background will be the use of high-speed cameras to measure the position of many beads simultaneously. Rather than the signal being derived from one bead, it is the correlated motion of the beads that distinguishes the sensor response from the uncorrelated background. We envisage two basic configurations. In the first, simplest case, the beads will be positioned at the ends of defined flared microfluidic structures to measure molecular interactions resulting from mechanical biological systems (molecular motors). Alternatively, we will create a circular array around the test object and measure the radial breathing of the ring. In this latter configuration there is the possibility of being able to make new and exciting biological measurements in a non-contact mode, where we will determine both short and long range interactions between cells and surfaces.

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1,167 Projects
  • Funder: UKRI Project Code: G0601295
    Funder Contribution: 1,222,890 GBP

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

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  • Funder: UKRI Project Code: BBS/E/C/00004947
    Funder Contribution: 569,194 GBP

    Most insects respond to each other and to other organisms within their environment. Many of these interactions are mediated by volatile chemicals which act as signals without having a direct physiological effect. Such semiochemicals may elicit a specific response in the same species, for example the sex, alarm and aggregation pheromones produced by many insect species. Other signal chemicals are produced by one species and cause a response in another (allelochemicals), for example chemicals from host organisms which attract insect pests and chemicals from non-hosts which are repellent. Such allelochemicals are responsible for the location of hosts by both crop pests and insect vectors of animal/human diseases. We are studying the genes and proteins involved in the interaction between insects and semiochemicals. This involves cloning and characterising genes encoding insect odorant-binding proteins (OBPs), chemosensory proteins (CSPs) and odorant receptors (ORs). The OBPs (and possibly CSPs) are involved in the initial binding of signal molecules within the antennae and transfer of the odours to the ORs and there is good evidence that these proteins confer some of the specificity of the insects' response to the signals. Using bioinformatic techniques we have identified genes encoding OBPs and CSPs from fruit flies, mosquitoes, moths and aphids and are determining which are expressed in antennae (using quantitative RT-PCR) and could therefore be involved in olfaction. The candidate genes are then cloned and expressed into recombinant proteins and these can be purified for ligand-binding studies. A range of techniques to identify which semiochemicals interact with which OBP are being developed and we are also developing new ways to study ligand/OBP/OR interactions. The functionality of the genes identified can be determined by gene silencing techniques combined with electrophysiological/behavioural assays.

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  • Funder: UKRI Project Code: EP/G010420/1
    Funder Contribution: 155,137 GBP

    In England, approximately 110,000 patients suffer a stroke each year, and at least 300,000 people live with moderate to severe disabilities as a result. The direct cost to the NHS of stroke is estimated to be 2.8 billion per year, with additional costs of informal care around 2.4 billion. Stroke accounts for about 11% of deaths, and around half of the survivors depend on others for everyday activities. Further research to reduce the incidence and long-term consequences of strokes on patients' lives is clearly called for. The brain requires a constant supply of blood to ensure that sufficient oxygen and nutrients are always available, and waste products produced by active cells are rapidly removed. A complex control system that dilates and constricts small arteries in the brain achieves this efficiently in healthy humans. This system, which is still poorly understood, responds to changing blood pressure (e.g. during exercise or when standing up), changes in breathing pattern, and variations in brain activity (e.g. waking / sleeping or responding to sensory stimuli). If the control system fails (e.g. following trauma or in premature babies), the subject may suffer from insufficient or excessive blood flow, either of which can lead to temporary or permanent brain damage, provoking strokes or aggravating their consequences. It is important to detect impairment of the control system early, in order to ensure appropriate care for the patient, such as keeping their blood pressure constant to avoid further brain damage. However, it is very difficult to measure whether a patient's blood flow is adequately regulated. Techniques that are currently used may require the patients' blood pressure to be changed quite considerably, but this cannot be done safely in vulnerable subjects. Procedures used are often uncomfortable and results not very reliable.We are proposing new experimental methods that are less aggressive and therefore might in the future be used in a wider group of patients. These methods use a variety of repeated small random changes in blood pressure (and also inhaled carbon dioxide concentrations), rather than larger swings. Extending previous work carried out by our teams in Southampton, Leicester and Norwich, we will simultaneously record blood pressure (using non-invasive methods) and blood flow in two arteries in the brain (using Doppler ultrasound applied on the outside of the head over the temples), together with CO2 in breathed air. From the small fluctuations in the prolonged recordings of these signals, we will estimate the characteristics of the system controlling blood flow, and in particular whether it is operating adequately, or is impaired. We will only carry out the experiments on healthy adult volunteers, and will provoke temporary impairment of the control system, by inhalation of air with increased levels of CO2, a procedure that is quite safe in the controlled laboratory conditions.In addition to developing new experimental methods, we will also develop and apply novel mathematical and computational techniques for signal-data analysis, which we believe will be more effective for the data we are investigating. Advanced statistical methods will be used to analyse results, and distinguish the known random variations between subjects (and also in repeated test in the same subject), from significant changes. In this joint project, we will be able to compare a number of different experimental methods and data processing techniques, in order to identify the ones with the best performance.In summary, the aims of the project are to investigate and develop new experimental protocols and data analysis methods, in order to provide new techniques that can be used to assess patients' brain blood flow control. We also expect this work to help understand better, how the control system works in healthy human subjects. As outcome we expect to recommend one or more new methods for future use in hospitals.

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  • Funder: UKRI Project Code: NE/F004753/1
    Funder Contribution: 270,485 GBP

    Rivers have (rather controversially) been described as 'simply outcrops of groundwater'. Many of the rivers in the UK are supplied mainly from groundwater sources, especially during the summer months when rainfall is characteristically low. The hyporheic zone is a critical interface between surface and subsurface waters in groundwater catchments. Here, the mixing of groundwater and surface water and the resulting biological and chemical reactions, may exert a lot of control on the water quality of the river and also its ecology: so much so that the hyporheic zone has been ascribed pollutant attenuating properties by some. Groundwater abstraction, effluent disposal and diffuse nutrient pressures - especially nitrogen - may all compromise the capacity of the hyporheic zone to influence the water quality of a river. Although quite a few researchers have recognised that the hyporheic zone has some special control on the river habitat, most have looked at it only from the perspective of the relationship between river water and the upper few centimetres of the sediments of the riverbed. They have ignored the fact that as well as downward flux from the river into the sediments of the riverbed there will also be upward flows from groundwater through the hyporheic zone and into the river. We are especially interested in what happens to the chemistry of groundwater as it moves through the hyporheic zone. We will look in detail at the relationship between different nitrogen species, such as nitrate and ammonium and chemical reactions known collectively as 'redox' or reduction-oxidation reactions. Redox reactions use electron acceptors other than oxygen for organic carbon oxidation as the amount of oxygen in the riverbed sediments is exhausted. These reactions and their relationship with nitrogen are important because the hyporheic zone has been proposed as a zone in which nitrogen attenuation occurs. This has led to the proposition that the movement of groundwater through this zone will reduce the concentration of nitrogen reaching the river water. In this project, we will investigate further the claim that the hyporheic zone can attenuate groundwater contaminants such as nitrate. We want to look much more carefully at the pattern of flow from groundwater through the hyporheic zone. We propose that groundwater flux is influenced by the permeability of the river bed and this is in turn influenced by the physical structure and topography of the riverbed. We believe that where the permeability of the riverbed is high and flux from groundwater towards the river is high, we will find different patterns of biogeochemical activity in the hyporheic zone compared to where the permeability is low. We like to think of the riverbed rather like a cheese grater with fast and slow flow pathways corresponding to 'holes' in the riverbed. We expect these holes to be quite dynamic as winter storms change the superficial topography of the riverbed sediments and rearrange the patterns of pool-riffle and fast-slow flow features in the underlying sediments of a river. The reason why these flow pathways are important is they may allow 'hotspots' of biogeochemical activity within the hyporheic zone that could be important controls on the ecology of groundwater-fed rivers because they either release or transform nitrogen through processes such as nitrification or denitrification. The latter converts nitrate, which can damage the ecology of a river where it is present at high concentrations, into nitrogen gas, which is harmless. If we are able to show clearly how important the hyporheic zone is in influencing the water quality in rivers that are groundwater-fed, we will be able to provide evidence that can be used to protect this zone, and can also be used in helping the UK meet the requirements of critical European legislation such as the Water Framework Directive.

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  • Funder: UKRI Project Code: G0800250
    Funder Contribution: 450,000 GBP

    In vitro fertilisation (IVF) and associated technologies remain relatively inefficient and costly and the problems worsen with increasing maternal age. One of the main reasons for these low success rates is poor oocyte (egg) quality, as we know very little about the biology of mammalian egg development and the factor(s) which make eggs fertile. This issue is exacerbated by the limited available of human eggs for research. In order to improve the success of assisted conception treatments we need to maximise the number of good quality eggs we collect from a woman?s ovaries but we must be careful that egg quality does not suffer at the expense of egg quantity. The current momentum in assisted conception is therefore to produce a small number of good eggs from each patient and so maximise their change of a pregnancy. However, this goal can only be achieved if we can identify the best eggs for IVF and use this information to improve patient treatments and so maximise egg quality. The objective of this project is therefore to measure egg quality in healthy women and to use this information to establish a cellular and molecular signature of egg health from patients with defined causes of infertility. The project aims to: (1) define and link biochemical and metabolic markers of egg quality; (2) investigate a number of key genes which may contribute to egg health; and (3) measure the impact of different assisted reproduction treatment regimes on egg quality. Some aspects of the research will be conducted using cow eggs as these tissues are a good model for human egg development; other components of the project will be conducted using human eggs which have been donated for research by infertility patients. We have already developed and validated the molecular biology methods and assays of egg protein turnover and energy metabolism which will be utilised on this project to measure egg quality. The data generated by the proposed studies will significantly advance our understanding of human egg biology and will ultimately help reduce the cost and improve the success rates of assisted conception treatments.

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  • Funder: UKRI Project Code: EP/F007426/1
    Funder Contribution: 3,148,360 GBP

    The first phase of the SUE Programme has focused necessarily on the present, assessing current solutions and their application in the near future, thus providing a strong empirical base on which to build. There now exist both the need and a sufficient body of work to extrapolate the findings to establish and test alternative urban futures: to create a variety of scenarios, building on prior and new work, and predicated on different fundamental assumptions and priorities; to assess those scenarios in terms of design, engineering implementation and measurement of performance; to refine them, in terms of mitigation and adaptation measures, incorporating novel solutions; and ultimately to provide alternative solutions with an associated evidence base and strategies for their implementation. This bid seeks to integrate the outputs of three current SUE consortia (Birmingham Eastside, VivaCity 2020 and WaND) and complementary research on the use of trees to mitigate the effects of atmospheric pollution. The team will work across disciplines to envision and establish alternative futures (using extensive literature on this subject and prior WaND consortium work) and construct scenarios that might flow from each alternative future. The various work packages will then focus on testing specific dimensions of each alternative future vis a vis their design, implementation and performance in the context of case history sites. Each project will engage an expert panel of influential stakeholders who will meet six-monthly to test and help shape new ideas, the chairs of each of the expert panels forming the higher level project steering committee. Panel consultation will be followed by interviews of stakeholders on motivations and the decision-making process, and specific empirical research and modelling. The following high level questions will be addressed via this process: - How does the ab initio conceptualization of sustainability influence design outcomes (e.g. form, density)? How would outcomes change if urban renewal were predicated on either environmental or social or economic overriding drivers? - How does development impact on its environs, and vice versa (e.g. is a 'sustainable' site good for the city / region / country and, if so, in what ways?) and is there an optimum development size to yield optimally sustainable outcomes? - Push versus pull to achieve sustainable outcomes. Much of what is done is thought good (for individuals, society, the environment), what might be wanted (push). Thus decisions are made and people must decide whether or not to take ownership. Might more sustainable outcomes follow if those who must take ownership dictate what is created (pull)? Birmingham Eastside will be used both to develop sustainability ideas and to test them on sites at various stages of planning and development (the research team has unparalleled access via its partnerships with key stakeholders involved in Eastside). Lancaster (with Morecambe, population 96k) and Worcester (94k) will be used to test the outcomes at the scale of smaller urban areas (e.g. market towns) but no attempt will be made to build comprehensive databases as at Eastside. Several other UK and international urban areas (including Sao Paulo, Singapore and an urban area in India) will be used to test a sub-set of the project's findings to assess the transferability of the scenarios to a variety of contexts and thus their general applicability.

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  • Funder: UKRI Project Code: NE/F002971/1
    Funder Contribution: 326,620 GBP

    The ocean plays a central role in the global carbon cycle. Uptake of carbon dioxide by the oceans has reduced the increase in atmospheric carbon dioxide that has arisen from fossil fuel burning and deforestation. It has long been know that the ocean biota play a major role in sequestering carbon dioxide on very long time scales (>1000 years). Recent evidence also suggests that the ocean biota play an important role on shorter time scales (10-100 years) as well. The balance between phytoplankton photosynthesis and community respiration determines the ability of the oceans to take up carbon dioxide. Nitrogen is generally considered to be the nutrient that limits phytoplankton photosynthesis. But what limits the amount of N in the ocean? Unlike most phytoplankton, which are N-limited, nitrogen fixing cyanobacteria have an unlimited supply of N. This is the N2 gas that is dissolved in seawater. Nitrogen-fixing cyanobacteria play a significant role in ocean nutrient and biogeochemical cycles as they are a major source of N, providing N for up to 50% of primary productivity in the most nutrient impoverished regions of the ocean. Nitrogen fixation is a key process that modulates the ability of the oceans to sequester carbon dioxide on time scales of 10 to 10,000 years. Limitation of nitrogen fixation results in lowered N availability for other primary producers reducing the potential of oligotrophic oceans to sequester carbon. This brings us to the issue of 'What limits the amount of nitrogen fixation in the ocean?' Amongst the environmental factors that may limit nitrogen fixation are temperature, light, carbon dioxide concentration and P- or Fe-limitation. It is argued that whereas N is the proximate limiting nutrient for phytoplankton photosynthesis in the sea, the ultimate limiting nutrient is either P (or Fe) because this nutrient limits the amount of nitrogen fixation. This proposal will examine the effects of light, carbon dioxide, P-limitation and Fe-limitation on photosynthetic properties and nitrogen fixation of nitrogen-fixing cyanobacteria. Research will be conducted under defined culture conditions in two species. One of these species, Trichodesmium, is documented to be of global significance. In addition, nitrogen fixation by unicellular cyanobacteria has recently been recognized to be significant. Therefore, the second species is one of these unicellular nitrogen fixers, Crocosphaera. The outcomes of this study will provide new insights into the mechanisms by which phosphorous and iron limit photosynthesis and nitrogen fixation in cyanobacteria. It will also provide new insights into the interaction with environmental factors such as light and carbon dioxide. This research will ultimately assist with several aspects of oceanographic studies on nutrient cycling and modeling the future importance of the oceans as C sinks.

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  • Funder: UKRI Project Code: EP/F064802/1
    Funder Contribution: 1,312,770 GBP

    The challengeHuman error and systemic failure lead to unnecessary harm and suffering for patients, including permanent impairment and loss of life. Research indicates that in up to 10% of all hospitals admissions some kind of adverse incident occurs, more than half of which are believed to be avoidable. The effect on staff and the 2billion+ consequential costs further increase the need to improve all aspects of patient safety. A significant contributory factor is that healthcare processes have undergone many revisions in recent years, while the design of much non-surgical equipment remains largely unchanged. Modern healthcare involves a combination of processes and procedures supported by a broad range of equipment and products that have to co-exist within the 'patient cubicle' or ward treatment space. Few of these have been designed to ensure safe integration within the context of use, be it ward, theatre, or community, nor is this a purchasing requirement within NHS Trusts. In short, current treatments are not properly and effectively supported by available equipment. Research aimsThe outcomes of this research will be both patient and system aware. The aims are to enhance patient safety in hospital by designing out medical error, to ensure that medical products and equipment are fit for purpose, and to contain risks associated with the introduction of new designs into a system of great complexity. The Chief Medical Officer recognises the potential of a design-led approach to patient safety and wishes to see it adopted more widely across the NHS. To design out medical error it is necessary to: (i) understand healthcare process demands with regard to diagnostic, monitoring and treatment routines, in particular in terms of the consistency and usability of interfaces and other features, and in light of the progressive introduction of 'smart' products and equipment; (ii) translate that understanding into a knowledge base for the design of medical products and equipment that support safer and more effective healthcare processes; (iii) establish a best-practice, evidence-based approach to the design, equivalent to that underpinning the development of treatments, procedures and medication regimes in modern medicine. Research approachWe will use both global and candidate approaches in the project. The global approach will follow a systematic methodology to capture the broader system of healthcare process and ensure there are no gaps in our understanding of the patients/system interactions. In addition, we identified from our clinical observations and design perspective, three candidates that require detailed attention in the project: (i) the communication process in the ward; (ii) the patient local environment personal cubicle and (iii) the ward clinical activity.In order to address the broader challenge of equipment and products in use on the hospital ward, a Consultant Surgeon and Clinical Reader at Imperial, Mr George Hanna, who has research interest in ergonomics, instrument design and surgical safety will lead the clinical side of the programme. Professor Charles Vincent will lead on healthcare process and patient safety aspects, and PhDs will be attached to each of these strands to build up a cadre of young researchers in the field.DeliverablesThe project will have the following deliverables (i) a thorough map of healthcare processes both on a ward and within the broader context of the patient journey (ii) comprehensive knowledge of the design requirements for ward equipment; (iii) design proposals for a ward communication system, (iv) design proposals for a ward treatment space or 'patient cubicle' and (v) guidelines for safe ward activities and staffing levels.

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  • Funder: UKRI Project Code: BB/F018193/1
    Funder Contribution: 72,540 GBP

    Fresh produce such as salad crops are generally grown outdoors in soil and irrigated by surface water abstractions. As a consequence crops are exposed to the risk of contamination by a range of pathogenic bacteria. Indeed, numerous outbreaks of gastrointestinal disease have been identified as being caused by ingestion of fresh produce so contaminated. Leading UK salad producers such as Vitacress go to considerable lengths to ensure pathogen-free soil. For example, no animal grazing or manures for 5 years pre cropping; no compost with animal manure for 2 years pre-cropping unless audited and tested batch by batch to prove free of Salmonella and low counts of E. coli etc. Consequently, there are many codes in place to ensure pathogen-free soil. However, it is recognised that outdoor crops will get contaminated, for example by animal intruders, birds, and of course poor quality irrigation water that has been contaminated up stream of abstraction. These vectors may potentially carry zoonotic pathogens such as Salmonella, E. coli O157 and Campylobacter. The risk of infection is much greater than for the majority of other food types because these are cooked or preserved by pickling, fermentation etc. At present, the most important means of sanitising fresh produce is by washing with chlorine post-harvest. However, there are safety and consumer preference concerns connected to the use of chlorine. Alternative technologies are beginning to be advocated, driven by the desire of large multiple retailers to get away from reliance on chlorine. These include the use of ozonation augmented with UV irradiation, hydrogen peroxide and citrox. There is now an urgent need to utilise our knowledge of microbial physiology and genomics to develop new procedures to assess the ability of these newer sanitisation technologies to decontaminate important foodborne pathogens on the fresh produce surface. Indeed, do motile pathogens migrate into stomata and below the leaf outer surface, making them more inaccessible to the currently used sanitisers? Do they interact, structurally or physiologically, with the microflora that is already present on the leaf in ways that might interfere with their removal or sanitation? An Industrial case studentship nearing completion has shown that for motile Salmonella, both of these mechanisms occur, and that these attached pathogens are highly resistant to disinfection and some become sub-lethally stressed by the treatments, making them difficult to recover using conventional culture techniques due to their viable but nonculturable (VNC) state. This VNC state may help explain why agents causing major outbreaks of foodborne disease go undetected at source. New microscopy and resuscitation techniques have been developed to assess the microbial quality of harvested salads, indicating the limitations of the current codes and growing practices in excluding natural biofilms and pathogens from the production chain, as well confirming that existing and novel sanitisation technologies are ineffective in removing any potential pathogen risk. Recent work has indicated that nitric oxide producing systems may have the potential to release biofilms and zoonotic pathogens from the salad leaf phylloplane, probably through interplay with their di-cyclic GMP regulatory pathways for attachment/detachment, and also now render them susceptible to conventional disinfection strategies. These observations will be confirmed for the agents of major salad borne outbreaks of disease, E. coli O157 and Salmonella enterica, and the mechanisms of the nitric oxide response at the phylloplane elucidated. This knowledge will be transferred into the salad processing factory environment to ensure the safe supply of salads to the public. The combination of microbiology, molecular biology and engineering expertise proposed in the project should lead to reduced incidence of disease transmission due to consumption of contaminated fresh produce.

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  • Funder: UKRI Project Code: EP/F040857/1
    Funder Contribution: 1,251,550 GBP

    Technologies associated with looking at the microworld are extremely mature, and include a wide variety of microscopies. By contrast little work has been done to extend our sense of hearing into the micro-world. The purpose of this grant is to develop a basic technology for listening to the micro world, in as sense a micro ear.Just like our own ears, most sound detectors respond to changes in pressure, creating small acoustic forces and corresponding displacement of a sensor. One extremely sensitive way of measuring force is to compare it against the momentum of a light beam. Tightly focused laser beams are now routinely used to form optical tweezers, which can trap micron-sized beads, overcoming both the thermal and gravitation forces. These tweezers systems are typically built around a microscope and manipulate samples suspended in a fluid medium / such that the technology is highly compatible with biological systems. Using a microscope to observe the bead position allows the measurement of piconewton forces and the corresponding displacement of a few nanometres. The subtle movements of these optically trapped beads will form the basis of our micro-ear. We plan to develop, demonstrate and test a number of different micro-ear approaches. All imaging systems based upon focusing are restricted to scales of a wavelength or so. Even in water, acoustic wavelengths are 100s mm, making the concept of focussing irrelevant to microscopic systems. However, as evident by most wind instruments or antique hearing aids, sub wavelength horns still work. In this proposal we plan to use microfabrication techniques to produce structures that channel the fluid flow from the emitting object to the sensor bead, providing a method of guiding the pressure wave, and if necessary amplifying it (e.g. in a flared channel). We will use the optically trapped beads as sensors to measure these forces (as described above). However, it is important to consider that, at the microscale, the movements of the beads due to an acoustic response may be masked by Brownian motion / and hence distinguishing the real signal from this thermal background will be a major challenge challenge.The key to overcoming the Brownian background will be the use of high-speed cameras to measure the position of many beads simultaneously. Rather than the signal being derived from one bead, it is the correlated motion of the beads that distinguishes the sensor response from the uncorrelated background. We envisage two basic configurations. In the first, simplest case, the beads will be positioned at the ends of defined flared microfluidic structures to measure molecular interactions resulting from mechanical biological systems (molecular motors). Alternatively, we will create a circular array around the test object and measure the radial breathing of the ring. In this latter configuration there is the possibility of being able to make new and exciting biological measurements in a non-contact mode, where we will determine both short and long range interactions between cells and surfaces.

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