NIHRDataInsights/HRCSData huggingface dataset:
Title: Examining the effectiveness and acceptability of the use of bio-fortified crops in alleviating micronutrient deficiencies in Pakistan
Funder: Arts and Humanities Research Council

Abstract: Dietary Zinc deficiency affects 17% of the world's population. In Pakistan, over 40% of women are zinc deficient (compared with less than 15% in Europe and North America). The health consequences of zinc deficiency are profound and long lasting, including stunted growth and impaired cognitive development in children, poor immune function in adults, ultimately limiting socioeconomic development. In order to address the Strategic Development Goals, it is imperative that a sustainable solution to zinc deficiency is found. Attempts to alleviate this problem include supplementation and food fortification, however both are inhibited by significant problems with compliance and efficacy. Another alternative is biofortification of staple crops which are widely consumed including by those with low purchasing power or social status. Recently, HarvestPlus scientists in Pakistan have been able to generate a "high Zn" variety of wheat using traditional breeding techniques that is adapted to Pakistan conditions. The variety (zincol/NARC421) contains up to 40 ug/g of Zn in the grain compared to traditional varieties that contain 23 ug/g of Zn in grains, on an average. This may be enhanced by the use of fertilizers. We propose to examine the potential of consuming this grain on improving zinc status in a resource poor community in northwest Pakistan. Using a double blind cross over design, grain will be provided to a total of 40 families (20 in each arm of the study). Control or biofortified grain will be made into flour, and consumed for a period of 16 weeks, with a crossover at 8 weeks. The impact on zinc status will be assessed using established (plasma and hair zinc concentration) and novel techniques (DNA fragmentation, nail zinc by laser ablation). The cultural acceptability of biofortification in Pakistan will be explored through dialogue with consumers, community leaders and farmers.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: GENERIC HEALTH RELEVANCE
Title: Traits and technologies to boost North African protein self-sufficiency (BEANS4N.AFRICA)
Funder: Arts and Humanities Research Council

Abstract: Uncontrolled spread of the parasitic weed, Orobanche crenata, across North Africa has led to a long-term decline in production of faba bean - a staple protein source - that impacts economic and nutritional welfare of smallholders and urban poor across the region. We propose a multi-disciplinary research program focused on this key legume, together with partners in Egypt and Tunisia, to simultaneously address: 1. the need for an efficient, high-throughput genotyping platform to make rapid progress in quantitative genetics, 2. The opportunity to exploit new discoveries and genetic resources that promise to deliver major breakthroughs in our understanding of the genetics of host tolerance to Orobanche, 3. the desire of well-trained geneticists in our partner institutes in Egypt and Tunisia to partner directly with the UK to deploy existing traits and technologies and 4. the recognition that adoption of new traits and varieties can be improved through a better understanding of barriers to uptake. Specifically, we will design and validate a 50K SNP genotyping array and use it do develop a high resolution genetic map based on a new multi-parent mapping population. High resolution genotyping and precision phenotyping of the Orobanche-faba interaction under controlled conditions will be combined to genetically dissect two distinct tolerance mechanisms - low strigolactone exudation and greater post-attachment competitive ability. Beside these mapping studies, we will also initiate a capacity-building breeding pipeline with our Egyptian and Tunisian partners to introgress two traits of immediate value - resistance to a sulfonylurea herbicide and low vicine-convicine (anti-nutritional) content - into locally adapted backgrounds. Finally, a socio-economic study of the agri-innovation systems in Tunisia and Egypt will ensure a better understanding by project participants of end user needs and involvement of stakeholders in designing ways to increase adoption rates and impact.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: GENERIC HEALTH RELEVANCE
Title: Development of a Bacteriophage Product to Control Campylobacter Contamination in Kenya
Funder: Arts and Humanities Research Council

Abstract: Kenya has the highest case fatality rate of campylobacteriosis, with 8.8% of infected people dying, mostly children. As in many other countries, poultry sources are the primary source of Campylobacter infection in Kenya, with studies demonstrating contamination in up to 77% of retail poultry samples in the capital city of Nairobi. The bacteria frequently reside in the intestinal tracts of chickens then spread to the surface of meat products during slaughter. Campylobacter-specific bacteriophage will be isolated in Kenya and characterised in preparation for their application against Campylobacter contaminating chicken meat in Kenya. While phages in North America are currently sold in liquid formats, a liquid phage product would be disadvantageous in Kenya due to the requirement for refrigeration and the bulk shipping and storing of liquid products is costly. A spray dried product will be developed that can incorporate a cocktail of phages for rehydration at the site of use. These studies will be undertaken in parallel with stakeholder engagement research.


Research activity codes: 3.4 VACCINES
Health categories: GENERIC HEALTH RELEVANCE
Title: Valuing Nature Programme Coordination Team
Funder: Arts and Humanities Research Council

Abstract: The concepts behind Valuing Nature are coming of age, emerging from the Millennium Assessment, and in the UK the subsequent UK National Ecosystem Assessment and the Natural Environment & Water White Papers published in 2011. Valuing Nature necessitates the bringing together of a wide range of disciplines: including the natural and social sciences, economics and the humanities. It also requires engagement from a broad range of business and policy interests. This presents significant challenges in cross disciplinary working. Building on lessons learnt in the first phase of the Valuing Nature Network (and through our Programme Advisory Goard, the RELU and BESS programmes and the HOPE initiative), this proposal aims to provide an innovative set of activities that will extend beyond the more traditional conference formats to include a) interactive sessions that build a shared understanding of concepts and vocabularies; and b) themed activities in partnership with other major consortia and initiatives in this field (e.g. NW+) (WP 1). We will also engage with key business and policy stakeholders designing events using interactive formats such as a) surgery sessions; b) dialogue sessions and c) 'unconference' events. The emphasis here is on mutual information exchange and learning, and will again be delivered in partnership with such organisations as NCI, Eftec and the KTN (WP2). Finally, our last work package (WP3) provides the behind the scenes building blocks to deliver such an interdisciplinary programme, including programme management, communications, data management, web site, monitoring and evaluating programme activies, and establishing a longer term legacy for Valuing Nature. The overarching aim of this programme is to provide the interdisciplinary science needed to put the value of nature at the core of the economy. This requires a truly integrated response to the research challenges posed involving the full range of constituents outlined in our proposal. If this is successfully implemented, then the impact of this research programme will be very significant in terms of the societal benefits it will bring.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Synthetic biology (SB) is defined in the UK Synthetic Biology Roadmap1 as 'the design and engineering of biologically based parts, novel devices and systems as well as the re-design of existing natural biological systems.' SB is both a platform technology and a translational technology (providing the link between a wide range of underpinning disciplines - ranging from biochemistry to systems biology - and practical applications in a wide range of different market sectors). We aim to pioneer the development of the underpinning tools and technologies needed to implement engineering principles and realise the full potential of synthetic biology in mammalian systems. We will 1. Establish a robust pipeline for the production and screening of synthetic transcription factors (sTFs) and synthetic chromatin editors (sCEs) based on the DNA binding domains of TAL effectors (TALEs) and the CRISPR/Cas system fused to transcriptional activators, repressors or chromatin modifiers e.g. histone deacetylases. 2. Create an in silico tool for designing small-molecule control of engineered protein and demonstrate the utility of this tool by producing novel drug-controlled proteins. 3. Assemble synthetic chromosomes and chromosomal safe harbors for introduction of synthetic genetic circuits. 4. Reduce contextual effects by building predictive models through characterizing circuit-chassis interactions at the single-cell level. 5.Engineer memory and computation synthetic genetic circuits in mammalian cells to a) deliver mechanistic information on the cell state, and responses to perturbations, e.g. drug treatments and count cell divisions. Underpinning this will be the development of standards for mammalian synthetic biology in collaboration with our partners NPL and take the concept of RRI in new directions to include: the politics of standardisation; the use of strategic mapping methodologies; and new approaches to engagement informed by speculative design.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Atomistic and Systems-level Modeling of Phosphate Catalysis
Funder: Biotechnology and Biological Sciences Research Council

Abstract: We will carry out computational studies of BRAF kinase and Ddl catalytic reactions using novel enhanced sampling algorithms, building on our recently developed accurate free energy calculation method that coupled Hamiltonian replica exchange with the finite temperature string method. We will continue to use MD and QM/MM calculations to study phosphate cleavage and transfer reactions that occur together with rate determining proton transfer processes. We will analyse the results from biased and unbiased dynamical trajectories using our newly developed Markov chain-based kinetic analysis method, DHAM. We will focus on the role of Mg2+ ions in the active site, and identify general features of this essential Mg2+ cofactor - using a systems-level approach - to better understand why magnesium is ubiquitously involved in the catalysis of phosphate cleavage and transfer catalytic reactions. We will use our calculated structures and mechanism to develop and test novel inhibitor design strategies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Novel enzyme diversity for improving cleaning and hygiene
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The technical approach is to use both bioinformatics mining and the screening of existing genomic libraries from the large DNA resource from thermophilic organisms and metagenomes accumulated from the recently completed EU Hotzyme project and other 'in house' resources available. The human sebum which is secreted daily from our bodies in not completely removed with the existing detergent enzymes. With knowledge of the human sebum composition the project will focus on the identification of the following 4 enzyme activities: (1) Novel carboxyl esterases and lipases since the conversion of triglycerides (TGs) to fatty acids found in sebum is only 70 % complete since the remaining 30% of TGs are non-saturated fatty acids that have poor affinity for the active site of the currently characterised TG lipases that are currently used in detergents. This is due to conformational restrictions of the cis-double bonds hindering the TG removal since the fatty alcohols do not carry a charge, which reduces the enzymes affinity for carboxylic acid products, which are likely to stay in the enzyme active site. (2) Cholesterol esterases - the Exeter group has previously solved a 3D structure of a novel potentially related esterase (Bourne et al.,2000). New novel cholesterol esterases will be mined from the genomic and metagenomics database. (3) Perhydrolases converting the available free fatty acids or carboxylic ester into an organic per-acid in the presence of hydrogen peroxide. This alpha/betahydrolase family member will contribute to the removal of superior sebum remnants and an improved hygiene by generating per-acetic acid for stain bleaching and will support the oxidation of the unsaturated fatty acids and triglycerides. (4) Squalene-hopene cyclase - converting squalene that is widely present in the human sebum into the sterol-like compound hopene.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: ELIXIR-UK Coordination Office
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The ELIXIR-UK Coordination Office will provide strategic and administrative leadership and support to the UK ELIXIR Node. ELIXIR-UK coordinates a wide range of activities across training in bioinformatics, data integration, and provision of tools and data involving 16 UK Universities and Research Institutes and expects to expand its activities further over time.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Direct Site Selective 19F- and 18F-labelling of Peptides and Proteins Towards "Zero Size - Zero Background" Bioimaging
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Postranslational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. In this context, access to precisely fluorine-modified proteins is incredibly useful for application in 19F NMR/MRI and in 18F PET bioimaging. Current methods towards fluorine-labelling of peptide and proteins employ often bulky prosthetics that could affect in a detrimental way the function of the biologics under investigation. Moreover, some fluorine markers suffer from stability problems, poor physicochemical properties, and long retention times of degradation products in the body, largely due to the instability issues of current fluorine labeling methods. The proposed research consists of developing novel F-labeling technologies that can serve both to label and to fine-tune the properties of 'biologics' both for superior bioimaging and function. We have designed a "zero-size zero background" method that will allow for direct precise and site-selective protein-CF3 bond construction. Validation studies will use readily available 19F prior to 18F radiochemistry enabling at each stage the generation of diversely applicable tools (NMR, MRI, PET). Our trifluoromethylation strategy targets cysteine or dehydroalanine residue, and will control both chemical reactivity and site-selectivity; these stringent conditions will be met with the availability of 18F-trifluoromethylation reagents of tunable reactivity. The novelty of our approach is the development of a linker-free technology that modifies peptide and proteins with the unnatural CH2SCF3 and CH2CF3 side-chains for application in bioimaging as the minimal symmetrical multi-fluorine group that is possible: CF3. The proposed late stage 19F- and 18F-trifluoromethylation of peptide and proteins with CF3-reagents, if successful, would represent a new departure in imaging science.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Structural data-mining of high-resolution 3DEM maps in EMDB
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The proposed research aims to develop methods and corresponding software for selection and validation of a set of reliable, high-resolution cryo-EM maps and corresponding atomic models, segment maps with the help of atomic coordinates and identify sections of the maps corresponding to small fragments. Segmented map fragments will be aligned and resolution-dependent classification will be carried out. Developed methods and derived data will be implemented in user-friendly software tools. The main methods to be used are advanced tools from modern statistics as well as from image processing and analysis. These methods include multivariate data analysis including multi-dimensional scaling, principal component analysis, alignment in rotational groups (special orthogonal groups in three-dimension - SO3 groups), procrustes analysis and classification techniques. The objectives of the proposed project are: 1) To develop methods for selecting EMDB entries with fitted atomic models, segmenting the EM density using the fitted model as a guide and aligning, classifying and averaging the segmented densities to obtain 3D density-motif libraries. 2) To explore variations in motifs as a function of resolution and environment to better understand the information content of EM structures. 3) To exploit the motif libraries to develop validation metrics based on the comparison of atomic models and motif densities. 4) To develop a production process to periodically update motif libraries as new entries are added to EMDB, and to provide versioned, open, public access to the motif libraries.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Hybrid 1H/19F Magnetic Resonance Imaging at 7T
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Non-1H MRI suffers from low signal to noise ratio (SNR) due to the lower concentration in the tissue and/or the lower gyromagnetic ratio of non-1H nuclei. Because of this, dedicated and optimized RF hardware solutions are often not available for non-proton MRI, but multi-nuclear MRI is becoming more attractive with the advent of ultra high field (UHF) scanners. Pre-clinical studies have shown that 19F imaging using perfluorocarbons has potentially many applications such as non-invasive oximetry in tumours, or the monitoring and diagnosing inflammatory process. In addition, 19F MRI does not suffer from background interference because 19F is not endogenously present. However, 19F MRI has not found application in humans because of the lack of a clinically approved fluorinated contrast agent and the low SNR of 19F MRI methods. We propose to design and build a novel design for a hybrid 19F/1H RF coil to address the challenge of low SNR in 19F MRI. A perfluorocarbon emulsion developed in Glasgow is currently undergoing clinical trials and can potentially address the problem of the lack of a clinically approved 19F contrast agent. We propose the development of a novel RF coil design that will allow hybrid 1H/19F MRI to take advantage of the increased SNR of our soon to be installed (early 2017) state-of-the art UHF scanner. Compared to conventional dual tuned design approach which compromises coil performance, we use a combination of a novel switchable coil for 1H/19F transmit and a 24-channel 19F receive array for increased SNR. Furthermore, due to the dual-frequency operation, the subject does not need to be repositioned on a different coil for co-registration and B0 shimming; improving patient comfort, reducing scan time and improved image quality. The coil performance will be validated using phantom models and the complete RF hardware will be validated for human use as per the guidelines of the local ethics committee.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: 'Gel-to-Grid' cryoEM of membrane proteins using SMALP technology
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Membrane protein structural biology has remained frustratingly challenging with only 1 atomic structure of a membrane protein being produced for every 50 soluble protein structures. This is in a background where more than 50% of therapeutics are targeted at a membrane protein. The lack of progress in membrane protein biology has resulted from a number of technical challenges in the production and structure solution process. Over the last 10 years these technical challenges have been addressed one by one. In 2009 we solved one of these technical challenges by developing the first detergent free method for extracting membrane proteins for purification. The method uses a low cost polymer based on Styrene Maleic Acid (SMA) that can insert into membranes and excise a 10 nm diameter disc (SMALP) that contains a membrane protein solvated by its local lipid environment. We have shown that the method can successfully extract a range of active, stabilised membrane proteins from a range of membranes. We have used these SMALP solubilised membrane proteins in single molecule electron microscopy studies to produce structures of these proteins. In the last 5 years atomic resolution EM has shown that atomic resolution structures can be produced from < 1,000,000 particles. Our SMALP method has the potential to complement this new method but our current protocols are suited to proteins that can be expressed at a reasonably high level. In this project we aim to exploit a recent observation that SMALP proteins can be separated intact on native PAGE. We have also shown that the resulting SMALP-rich band can be directly transferred to an EM grid and used for imaging. We will explore whether this technique can be extended to drastically reduce the amount of membrane required to generate a structure by EM thereby removing one of the remaining technical technical challenges that have limited our knowledge of membrane protein structure.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: GENERIC HEALTH RELEVANCE