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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

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Integrated Rapid Test Platforms Appropriate for the Developing World

David KelsoNorthwestern UniversityEvanston, Illinois, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
1 Aug 2006

In the developing world, many people with health problems never receive an accurate diagnosis or appropriate treatment because clinicians lack tools to detect and diagnose diseases and conditions quickly, accurately, and inexpensively. Sophisticated medical tests that could help improve care are not only often unaffordable, they require extensive laboratory facilities and deliver results days later – a hardship for people who may live many miles from the nearest health clinic. Dr. Kelso's team is developing rapid, affordable, point­-of-­care systems for both immunological and molecular tests. The project's objective is to design low­-cost delivery platforms that can perform assays in resource­-poor settings.

Finding Solutions to Thrive After Birth Asphyxia in Africa

Pia WintermarkResearch Institute of the McGill University Health CentreMontreal, Quebec, Canada
Grand Challenges
Annual Meeting Call-to-Action
1 Mar 2019

Pia Wintermark of McGill University in Canada and Cally Tann of the London School of Hygiene & Tropical Medicine in the United Kingdom will establish a pilot cohort in Uganda of term newborns who suffered from asphyxia at birth, which means that their brain and other organs did not receive enough blood or oxygen, and conduct a clinical test of a novel neurorestorative agent (i.e., to repair brain injuries) to see if it can improve early brain development in this setting. Birth asphyxia and the resulting neonatal encephalopathy is the third leading cause of mortality in infants under five and leads to significant brain damage and long-term neurodevelopmental morbidities. In a rat model of term neonatal brain damage, they found that a compound, sildenafil, reduced brain damage and inflammation, and increased nerve cell growth. This compound has already proven safe for use in humans for other purposes. They will first assemble a pilot cohort of 100 neonates with neonatal encephalopathy in Uganda, and clinically evaluate them over the first three months of age to better characterize the disease in this setting. From this cohort, 30 newborns will be selected to test whether daily treatment of sildenafil from day 2 to day 9 of life can improve brain growth and development and is a feasible and acceptable neurorestorative treatment strategy in this setting.

WRKY This Way: A New Way to Tackle Biotic and Abiotic Stress

Alison BentleyNational Institute of Agricutltural BotanyCambridge, United Kingdom
Grand Challenges
Annual Meeting Call-to-Action
1 Mar 2019

Alison Bentley of the National Institute of Agricultural Botany and Ari Sadanandom of the University of Durham both in the United Kingdom will examine whether a new molecular link that they found explaining the increase in plant diseases (biotic factors) associated with high nutrient levels (abiotic factors) can be exploited to maximize wheat crop yield with minimal negative impact on the environment. Wheat, one of the first domesticated food crops, has been grown for over 10,000 years and is critically important to global food supply. Traditionally, crop yields are maximized by applying nitrogen fertilizer to stimulate growth, and fungicides and pesticides to prevent disease. These approaches are expensive and can harm the environment. Another complication is that increasing amounts of nitrogen fertilizer also increases the occurrence of disease. They have identified a group of transcription factors (TFs) - proteins that control expression of specific genes – that appear to protect plants against the fungus Septoria specifically under varying nitrogen levels. To investigate this, they will create transgenic wheat to increase or decrease each TF and explore the effect on disease resistance and growth in different concentrations of nitrogen. Understanding this relationship will allow them to boost plant resistance to disease under high growth conditions, and thereby optimize crop yield with maximal economic gain and minimal environmental impact.

Lactoferrin for Neuroprotection of the Developing Brain

Anne CC LeeBrigham and Women's HospitalBoston, Massachusetts, United States
Grand Challenges
Annual Meeting Call-to-Action
1 Mar 2019

Anne CC Lee and Mandy Brown Belfort of Brigham and Women's Hospital in the U.S. along with Stéphane Sizonenko and Petra Huppi of the University of Geneva in Switzerland will test whether lactoferrin, a breast milk nutrient, can promote growth and reduce injury in the developing infant brain. Of the 15 million annual preterm births, almost a million of the surviving babies have severe neurological defects such as cerebral palsy. However, there are limited treatments available. Breast milk has a positive effect on the infant brain, but the mechanisms for this are unclear. Their preliminary data showed that lactoferrin, a glycoprotein found in breast milk, has a neuroprotective effect in several rat models of neonatal brain injury. They will build on this to study the effect of different concentrations of lactoferrin in the rat models, as well as assaying candidate inflammation, cell death, and neurotrophic factors to identify the molecular mechanisms involved. They will perform a human observational study to associate the different levels of lactoferrin found in breast milk samples from a cohort of mothers of preterm infants at Brigham and Women's Hospital with the infant's brain development as assessed by magnetic resonance imaging. They will also measure lactoferrin levels in samples collected from 100 mothers in Bangladesh to see how they compare. Together, they will generate essential data on lactoferrin for future human clinical trials in low- to middle-income countries.

Virtual Reality High-Resolution Expansion Imaging of Infectious Disease

Caroline StefaniBenaroya Research Institute at Virginia MasonSeattle, Washington, United States
Grand Challenges
Annual Meeting Call-to-Action
5 Mar 2019

Caroline Stefani of the Benaroya Research Institute at Virginia Mason and Yongxing (Leon) Zhao of Carnegie Mellon University both in the U.S. will build an imaging platform combining expansion microbiology and confocal virtual reality to visualize complex host-pathogen interactions in infected tissues to help develop new diagnostics and therapeutics. It is the molecular interactions between the host and the pathogen, both in tissues and inside cells, that ultimately dictate whether an infection takes hold or is destroyed. Identifying these interactions could help develop new treatments. However, they remain difficult to study in sufficient resolution. They have developed a new method for three-dimensional visualization of confocal microscopy images using commercial virtual reality technology to pinpoint the subcellular localization of host-pathogen interactions. They will combine this with a new technique, expansion microscopy optimized for microbiology (ExMicro), which visualizes nanoscale details of dozens of different molecules in infected tissue by embedding it in a polyacrylate-based polymer that can be expanded in pure water to improve resolution. They will develop protocols and software to optimize both methods for studying host-pathogen interactions, and build a platform to share their new toolset with the scientific community.

Minimal Genomics Lab for AMR Surveillance and Diagnostics in Provincial Low-income Settings

Iruka OkekeUniversity of Ibadan, College of MedicineIbadan, Nigeria
Grand Challenges
Annual Meeting Call-to-Action
8 Mar 2019

Iruka Okeke of the University of Ibadan, College of Medicine in Nigeria and Kat Holt of Monash University in Australia will set-up a remote laboratory that uses nanopore sequencing as a low-cost, portable method to monitor the spread of antimicrobial resistance in rural areas of Africa and combine it with genome editing tools for more rapid diagnosis and improved treatment. Antimicrobial resistance (AMR) occurs when pathogens are able to survive treatments that previously would have killed them. Infection persists in these patients and spreads to others in the community, increasing both the risk of serious complications and the economic costs. To combat AMR, it needs to be tracked locally and quickly enough to inform treatment. However, traditional tracking methods are slow, and difficult to use in rural settings because of limited resources. Nanopore sequencing technology is a highly portable method of sequencing DNA that is suitable for resource-poor settings. They will setup a prototype minimal bacterial genomics lab at a provincial hospital laboratory in Africa, and use nanopore sequencing to catalog pathogens collected from patients and monitor AMR. They will also combine the sequencing with a genome editing tool - CRISPR-Cas - to enrich for known resistant pathogens and enable much faster diagnosis directly from blood or stool samples. Once optimized in the initial location, the remote lab can be recreated in other areas of Africa.

Global Burden of Crop Pests and Disease (GBCrop)

Cambria FinegoldCAB InternationalWallingford, United Kingdom
Grand Challenges
Annual Meeting Call-to-Action
13 Mar 2019

Cambria Finegold, Richard Shaw and Roger Day of the Centre for Agriculture and Bioscience International in collaboration with Katherine Derby of the University of York and Sarah Gurr of the University of Exeter all in the United Kingdom, will design a platform - GBCrop - to collect, analyze and disseminate data on the global impact of crop pests and disease. The fact that 40% of crops are lost to pests impacts both the global food supply and local economies. Despite this, little is known about why and how crop pests and diseases occur. The extent of the problem was acknowledged by the UN declaring 2020 the Year of the Plant. They will design GBCrop to collect large quantities of high-quality data and apply advanced analytical methods to generate results that can then be used to direct research and policy development, and to predict the impact of emerging diseases. The program is modeled after Global Burden of Disease, which has transformed health policy agendas over the last 25 years. They will begin by consulting with key experts, and then include policy makers, private industry representatives, government organizations, potential funders and scientific experts. Together they will decide what data to collect and how it can best be used to accurately predict the impact of emerging crop diseases. They will launch their plan-of-action in the Year of the Plant and aim to make their first recommendations in 2023 on how to maximize crop gains.

Investigating NETosis-Associated Proteins in Human TB Granulomas as Targets for Host-Directed Therapies and Prediction of Disease Progression

Mohlopheni MarakalalaAfrica Health Research InstituteDurban, South Africa
Grand Challenges
Annual Meeting Call-to-Action
13 Mar 2019

Mohlopheni Marakalala of the Africa Health Research Institute in South Africa will study the role of specific proteins associated with immune cell death in tuberculosis patients to better understand how the disease progresses and help develop new diagnostics and therapies. Tuberculosis (TB) is a bacterial disease that causes 1.5 million deaths per year, mostly in poor countries. Understanding how the human immune system responds to TB infection could help develop more effective, host-targeted treatments. Granulomas - tissues that form as a result of inflammation - are commonly seen in the lungs of TB patients. Their characteristics change as the disease progresses and they can cause severe lung damage. Granulomas are thought to be formed by the death of white blood cells called neutrophils, which are also abundant in the airways of patients. He will study granulomas isolated from patients at different stages of the disease to identify proteins linked to neutrophil cell death and see if they are linked with lung damage and disease progression. He will then determine whether the levels of these proteins in the blood can be used as disease biomarkers for the early detection of TB. Lastly, he will use molecular genetic techniques to reduce the level of these proteins in neutrophils and evaluate the effect on TB infection to see if the approach could be exploited as a potential therapy.

Establishing a Maker Space Co-Creation Program in Bahir Dar, Ethiopia

Sophie MowerThe Centre for Global Equality LimitedCambridge, United Kingdom
Grand Challenges
Annual Meeting Call-to-Action
15 Mar 2019

Sophie Mower of The Centre for Global Equality in the United Kingdom will establish a collaborative program for technology students at Bahir Dar University in Ethiopia using expertise and support from a number of other centers in Africa and beyond to provide training and financial resources for them to research and develop their own innovative solutions to local challenges. Students at the university work on creative solutions such as mapping applications particularly in areas of agriculture and health. However, advancing their ideas is limited by the lack of professional networks and material resources. They will provide a dedicated space at the university and work with the Centre for Global Equality (CGE) and companies in the Cambridge Cluster, both in the United Kingdom, and an African innovation hub. Together, they will provide training for 30 students on co-creating their solutions with end-users to increase their impact. They will also hold an ideation hackathon to generate design ideas, and award $2000 to the six most competitive projects. These will be supported through to prototype development using methods from an incubator approach established at the CGE.

Genetic Approaches to Malaria Control in Africa

Eric OchomoKenya Medical Research InstituteNairobi, Kenya
Grand Challenges
Annual Meeting Call-to-Action
18 Mar 2019

Eric Ochomo of the Kenya Medical Research Institute (KEMRI) in Kenya and Luc Djogbenou of the University of Abomey (UAC) in Benin will develop a curriculum to teach African scientists how to use genetic approaches to combat insecticide resistance in the fight against malaria. Malaria is a disease that kills almost 500,000 people annually, most in sub-Saharan Africa. People become infected when bitten by mosquitoes that transmit the disease-causing parasites. Insecticide treatment of bed nets and indoor areas are effective methods of disease control, but mosquitoes are becoming resistant. Varying the types of insecticides used and applying them in different combinations can help fight resistance, but it's difficult to know the most effective approach before resistance develops without the help of genetic markers. They will teach African scientists techniques to identify genetic resistance markers including sample collection and preservation, transcriptomic and whole-genome sequencing, and bioinformatics using online and hands-on approaches. This will ensure timely changes to insecticide application to better combat resistance. They will also encourage local scientists to establish industry partnerships to ensure that resistance monitoring can continue long-term.

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