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      "title_narrative":["Analysing the policy and governance environment for NCD control, and identifying potential policy options."],
      "description_narrative":["The Non-Communicable Diseases (NCDs) have emerged as the most important global threat to human health and wellbeing. Four major NCDs - heart disease, cancers, diabetes, respiratory diseases - cause the deaths of 38 million people every year, of whom 16 million die prematurely (under the age of 70 years). These diseases cause chronic illness and disability and are a source of suffering and financial hardship for individuals, families, communities and health systems struggling to provide continuous care for people with long-term health problems. The NCDs affect populations across the globe - and they are now the leading cause of death in many low and middle income countries.   Many of these diseases are driven by exposure to commercial products - tobacco, alcohol, highly processed foods (including the so-called 'junk foods') which have high levels of salt, sugar and/or trans-fats. Evidence shows that limiting exposure to these products is likely to bring health benefits, but it is often very difficult for individuals to sustain 'healthy behaviours' over their lifetime. Evidence-informed prevention strategies most likely to bring benefit to the largest numbers of people include: regulating exposure, e.g. taxation on products known to be health-reducing, such as sugary drinks; restricting access, e.g. no sales of tobacco to children, non-smoking zones in public spaces; or reformulating products to make them less likely to cause harm, e.g. lowering the salt content of processed foods. Such strategies, when implemented well, can have a significant impact on improving population health.   However, Governments face many challenges in implementing these policies - for example, there may be resistance from strong and powerful commercial companies that have a vested interest in selling their products. Moreover, in many countries, there is little policy experience in tackling the NCDs.   In this project we propose to undertake detailed policy analyses to identify acceptable and feasible options for Governments in both low- and middle-income countries to tackle the growing burden of NCDs in their countries. Our work will focus on three policy areas - control of sugar, salt and trans-fats in processed foods. We will work with researchers in Afghanistan, Bangladesh, Iran, Nepal, Pakistan, Tunisia and Vietnam to identify how the Government in each country is currently tackling NCDs. We will then map out the influences on policy options operating in each country. Such influences are likely to include the role of powerful stakeholders such as the food producing and selling industries, the media, the medical establishment, the Ministry of trade, etc. We will also identify whether any civil society groups (in some countries this might mean, for example, groups of parents concerned about junk-food marketing to children; in other countries it will include groups of patients suffering from diet-related NCDs such as diabetes) are working on policy issues. We will conduct interviews with key stakeholders to better understand the opportunities for seeing effective policy implemented for controlling sugar, salt and/or trans-fats, as well as identifying the challenges and barriers to putting effective policy options into operation.   This kind of health analysis requires a specific skill set which is not common in many countries. As part of our project we will therefore establish and strengthen the capacity of a network of researchers from all 8 countries (including the UK), who will support each other to carry out the analyses and interpret the findings. We will foster cross-learning of policy successes between different countries. In addition, we will promote engagement and dialogue with a wide variety of stakeholders in each country throughout the lifetime of the project in order to ensure that the findings of the research carry meaning and weight in policy decisions to improve population health both in the 7 research countries and beyond.","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":["Capacity building in dietary monitoring and public health nutrition in the Eastern Mediterranean Region Countries"],
      "description_narrative":["In common with many Western countries, the Eastern Mediterranean Region (EMR) has a major problem with obesity and the associated public health issues. The World Health Organization (WHO) has been developing new health policies to lower intakes of sugar, saturated fats, trans fats and salt with the aim of reducing the risk of non-communicable diseases (diabetes, cardiovascular disease and obesity) in children and adults. To implement these policies successfully it is essential to have high quality food composition and food intake data to underpin research into the links between diet and health and to enable effective dietary monitoring and policy development. Most EMR countries use international food composition tables that include foods consumed in western diets with different nutrient composition, especially for mixed and traditional dishes. Some of these data from other countries are outdated and do not reflect the composition of foods currently consumed in EMR countries, meaning that calculated nutrient intakes are inaccurate. Methods of measuring dietary intake also need to be up-to-date and use appropriate food information. This project intends to provide technical and scientific support for researchers (mainly food and nutrition experts) in LMIC countries in the EMR, and will also provide training in the use of improved standardized methods for production and management of food composition and food intake data and also identify appropriate biological markers of food nutritional value and measurements of health outcomes. A review will be undertaken of food and nutrient intakes in the LMICs to develop strategies for reducing sugary and fatty foods in these diets based on new WHO guidelines. The Quadram Bioscience Institute, that aims to develop solutions to worldwide challenges in human health, food and infectious disease and non communicable disease, will lead the project in partnership with the WHO EMR office. The latter will help to coordinate and co-align regional activities to ensure public health priorities are targeted effectively. Three main activities will underpin capacity building in the EMR with a focus on 10 target LMICs (Morocco, Tunisia, Egypt, Jordan, Palestine, Sudan, Lebanon, Pakistan, Iran & Afghanistan). The project will build on existing links with the WHO EMR and will develop and extend activities with LMIC in the EMR. Four main activities are planned: (1) Training and knowledge exchange workshops; (2) Short-term exchanges of researchers; (3) Development and application of harmonised protocols for pilot sample collection, food analysis, data generation and creation of online regional food composition datasets; (4) Development of possible dietary and other strategies to support reduction in intake of sugary and fatty foods. The main outcomes will be to build capacity and practical skills in the LMIC to improve production, management and use of food composition and dietary intake data, and biomarkers. Knowledge of European and International standards will be disseminated, with support from WHO, to experts across the region. Networks of expertise within the region will also be an important outcome leading to increased collaboration and effective data sharing. The project will enable more efficient use of better quality, region specific, food composition and intake data that can be used for research, monitoring and policy development. This will benefit LMICs in the region by providing data and tools that can encourage reduction of sugar, saturated fat, trans fats and salt and thereby reduce the incidence of diet related disease.","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":["Neglected tropical diseases are a diverse group of diseases that thrive mainly among the poorest of the world's populations. Three of the World Health Organisation's 10 most significant neglected tropical diseases - African trypanosomiasis (also known as sleeping sickness), leishmaniasis, and Chagas' disease - are caused by closely-related single-celled parasites. Human infection with African trypanosomes is brought about when an infected tsetse fly takes a blood meal. Without treatment the disease progresses through general ill health to coma and death. Current drugs in use against trypanosomes are old, toxic and failing due to emergence of resistance. Urgent new research is needed to identify potential new therapeutic options.  An unusual aspect of African trypanosomes is that they multiply in the human blood in full view of the body's defence systems. They do this by periodically changing their cell surface to escape recognition by the host. However, many molecules on the parasite surface perform essential functions and cannot be changed. Trypanosomes place these in a special, protected domain on the cell surface. Identifying surface-exposed invariant molecules and understanding how this protective segregation is maintained are of major scientific interest, as well as of practical utility in uncovering ways in which trypanosomes may be vulnerable to new therapies.  Using a combinatorial approach funded by the MRC, I have previously identified the composition of the African trypanosome cell surface. I now aim to exploit this knowledge to single out those invariant surface molecules that are essential to the survival of the parasite during infection. For this, I propose to harness some of the power of modern DNA sequencing technologies to test which cell surface genes, when silenced, cause the parasite to die inside the host. A similar method will be used to identify not only cell surface genes, but any genes that the parasite uses to maintain the cell surface organisation, which is so critical to escaping the host immune attack.   Finally, I propose to test those surface-exposed molecules for their potential as vaccines. My pilot experiments show that I can use genetically-modified parasite to screen for molecules on the parasite surface that are accessible to the immune system. I propose to develop this assay and test the most promising candidates in an animal model of human disease. The proposed work will increase our understanding of the fundamental biology of a significant human parasite, and also, by exposing essential surface molecules, provide the first steps in developing new treatments.","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":["G-quadruplex biology in the human malaria parasite Plasmodium falciparum"],
      "description_narrative":["The proposed research concerns the most important human malaria parasite, Plasmodium falciparum. Malaria is one of the world's most debilitating infectious diseases, killing over half a million people every year and affecting several hundred million. Most of the deaths occur in young children in sub-Saharan Africa, but adults can also suffer from malaria throughout their lives, reducing quality of life and retarding economic development in endemic countries. The lack of an effective vaccine and the emergence of drug-resistant parasites mean that there is now an urgent need for research leading to a better understanding of the malaria parasite, and hence to new vaccine targets and treatment strategies for this disease.  The malaria parasite causes illness via the infection of red blood cells. It multiplies inside these cells and modifies their surfaces with proteins called PfEMP1s that bind to the walls of blood vessels. This is crucial for parasite survival as it removes infected cells from the circulating blood and protects them from passing through the spleen, which might recognize and destroy them. It also contributes to disease, with severe malaria being particularly associated with the accumulation of infected cells in vessels of the brain and placenta. It is therefore of great interest to malaria biologists to understand the mechanisms that control the expression of these adhesive PfEMP1 proteins. PfEMP1s are not expressed uniformly by all malaria parasites: instead, individual parasites regularly switch between different variants. This allows them to stay ahead of the immune system and sustain a chronic infection for months or even years. The parasites have a large, variable family of 'var' genes for different PfEMP1 proteins and they vary the expression of these genes by so-called 'epigenetic switching'. Furthermore, var genes recombine very readily to generate new variants, so each parasite strain - of which there are many hundreds circulating in endemic areas - has a unique repertoire of possible surface proteins. This is one reason why immunity to repeated malaria infections is slow to develop in humans: every new parasite strain looks different to the immune system, so people can be re-infected repeatedly throughout their lives.  Understanding and ultimately interfering with the expression, switching and recombination of var genes, and thus the variant expression of PfEMP1 proteins, could be a key to more effective immune control of malaria. Therefore, this research focuses on a new biological mechanism that the parasite may use for switching between var genes and for generating new variants. Our recent work has showed that an unusual DNA structure called a G-quadruplex that is concentrated around var genes seems to affect both these processes. To investigate this further, we now propose to map the G-quadruplexes throughout the Plasmodium genome, both in DNA and also in the messenger molecule, RNA. We will use a range of cutting-edge genome-wide technologies to do this, and will then check whether the distribution of the structures changes when the enzymes that unwind them are removed.  These studies will lead to a better understanding of the mechanisms underlying var gene dynamics, and may ultimately inform new strategies to combat malaria, since var genes - and the adhesive proteins that they encode - are central to malarial disease. The outcomes of the research will be published in open-access scientific journals and presented at international conferences. They will be communicated to the general public via summaries on appropriate websites and via science writing in magazines and/or online. Work such as this remains vital as long as the malaria parasite continues to cause an immense burden of human disease.","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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