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      "title_narrative":["Identification of novel mechanisms of fetal-haemoglobin induction by common genetic variation in patients with sickle cell disease"],
      "description_narrative":["We aim to discover the molecular mechanisms by which benign common DNA variants at two genetic sites, BCL11A and HBS1L-MYB, influence fetal haemoglobin levels in adults. Fetal haemoglobin (HbF) is the oxygen-carrying molecule dominating red blood cells in the unborn. It is switched off around the time of birth and replaced with the adult form of haemoglobin. Since in patients with sickle cell disease (SCD) adult haemoglobin is defective, the ability of some adult patients to produce the fetal form will make the disease significantly milder. Much knowledge has been accumulated regarding the structure and function of the BCL11A and HBS1L-MYB sites. The HbF-affecting genetic variants reside in gene-regulating elements called 'super-enhancers' that control the activity of neighbouring genes in red blood cell precursors and thus affect their development and haemoglobin content. Little is known about how the naturally-occurring DNA changes affect the function of these 'super-enhancers'. Here, we aim to uncover novel regulatory pathways and identify transcription factors binding to genetically-variable enhancer elements. This will add to the arsenal of targets for new therapeutic approaches aiming at reactivating HbF in patients. In addition to guiding new gene therapy strategies, our results will help laying the groundwork for the development of new affordable drugs to benefit the patients suffering from SCD mainly in low-and-middle income countries, especially Africa, where more than 200,000 affected children are born annually. In the UK, the disease is present mostly through the African diaspora and shows significant clinical diversity, partially driven by the variable, genetically-determined presence of HbF.  Our experimental strategy will build on three major resources generated through collaboration: (1) four ethnically-diverse groups of well-characterised patients (n > 3,000) from the UK, Tanzania and Nigeria, where we will assemble extensive genetic data; (2) access to 2,000 genetically and haematologically characterised subjects from the TwinsUK cohort, where we will be able to obtain progenitor cells from 16 individuals with specific genetic profiles at BCL11A and HBS1L-MYB and (3) red blood cell producing cell lines carrying individual critical DNA variants generated through genome editing of the red blood cell-producing cell line BEL-A in collaboration with its creator, Prof Jan Frayne. Our principal goals are: (1) to genetically and functionally dissect common genetic variability at the two major quantitative trait loci for fetal-haemoglobin levels, BCL11A and HBS1L-MYB in order to unravel potentially novel molecular mechanisms through which genetic variation controls gene expression, determines HbF levels and influences the generation of red blood cells. A post-doctoral researcher recruited from our collaborators in Tanzania or Nigeria will investigate transcription factor binding (the techniques used will be EMSA - 'electrophoretic mobility shift assays', ChIP - 'chromatin immunoprecipitation') and chromatin looping (a folding of the DNA that occurs in active cells to position regulatory elements next to their target genes, the technique we will use is called '4C-seq') and gene activity in relationship with the genotype of the cells studied. (2) to identify the causal DNA changes at three independent subloci (HMIP-1, HMIP-2B, BCL11A-2) of the above through a combination of genetic mapping and functional studies. From these we will create a genetic score that can be calculated for each patient, aimed at predicting HbF levels and clinical severity in sickle cell disease. This score will become a parameter ascertained in genetic and clinical studies, including drug trials, helping to make such studies more informative; (3) to help build capacity and expertise for sickle cell research in Tanzania and Nigeria through training of researchers and building of extensive genetic datasets for their patient cohorts.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Implementing  innovative technology to tackle barriers in utilising human waste derived fertilisers in Sub Saharan African agriculture"],
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      "description_narrative":["For the more than 200 million farmers in Africa who depend on rain-fed agriculture, drought is a matter of life and death. Their vulnerability is often aggravated by a lack of access to risk management tools such as insurance, which also limits their ability to take productive risks on their farms. Index insurance, where compensation is based on weather or area yield metrics, rather than on measured losses, is an affordable alternative to traditional insurance. However, index insurance will only increase resilience to climate shocks if the index insured fairly reflects the risk for both farmers and insurers.   Index design processes are becoming increasingly sophisticated, utilizing multiple data-sources and models. A certain degree of basis risk (where compensation doesn't match observed losses) is, however, inevitable as insurance is not designed to target every risk. Anticipating basis risk that ensues from the complexity in the relationship between meteorological drought (rainfall deficit) and agricultural drought (soil moisture deficit) is a key challenge for the agricultural insurance sector.   We propose a new system, SatWIN-ALERT, which can be deployed in real time to detect and predict basis risk events as they happen. As such, it could unlock in-season actions (such as increased monitoring), or allow timely post-season index assessment or action, enabling aid agencies and governments to anticipate basis risk events, and take action to support farmers who are facing uncompensated agricultural losses. In effect, the facility to predict pay outs and losses bridges the gap between post hoc index insurance and forecast-based finance. SatWIN-ALERT provides a means of combining the data issued by existing platforms into integrated assessments of droughts and subsequent compensation. As such, it can be integrated into well-established and trusted insurance design systems, such as the ARC risk viewer (ARV) or the IRI Social Network for Index Insurance Design (SNIID).   SatWIN-ALERT builds on existing state-of-the-art practices to take a sophisticated approach to basis risk management, allowing index insurance to play an improved role within climate risk management and development. We also bring together novel existing participatory and meteorological research to build systems that are suitable for operational use in ODA countries. To do this, we draw on fundamental research on monitoring of environmental conditions, and on recent improvements in forecasts - especially on sub-seasonal to seasonal time scales, working with established partners to bring results to hundreds of thousands of farmers. We will focus on countries identified as important to our partners, specifically Malawi for our participatory research, plus Nigeria, Senegal, Malawi, Zambia and Ethiopia (amongst others) for our basis risk case studies.  In summary, the proposed project will develop a novel operational system (SatWIN-ALERT), which empowers farmers to benefit from robust financial instruments, based on state-of-the-art models, observations and forecasts. Partnership with leading practitioners in Africa will enable SatWIN-ALERT to sit within existing insurance systems to revolutionise basis risk management and build the resilience of millions of farmers to weather-related hazard.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "description_narrative":["The UKRI COVID-19 Grant Extension Allocation (CoA) provided organisations with resources to sustain UKRI grant-funded research during the period of pandemic disruption and its immediate aftermath. Some of the funding was directly used supporting the following ODA-eligible grants at Brunel University London: InnovateUK 105316 - Tassou; \nBB/R012695/1; \nBB/R012695/1; \nInnovateUK 42088 Singh  (SOFTS); \nInnovateUK  41760   Singh    (C-SPEL); \nInnovateUK 105669 Singh (INset4KTI); \nBB/P024149/1; \n InnovateUK 48979 Singh (SolCos).","Research and development activity contributing to the UK’s strategy to address key development challenges."],
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