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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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.
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.
David Hughes of Pennsylvania State University, John Corbett of aWhere, and Rhiannan Price of DigitalGlobe, in the U.S. will develop a software platform comprising prediction algorithms that leverage artificial intelligence to predict where and when plant diseases and pests will occur from weather and satellite data to alert farmers to check their crops. Pests and diseases are moving targets, however most current surveillance methods monitor only their presence or absence. Predicting when and where they are likely to occur would be more valuable for preventing them. This has recently been made possible by studies on how environmental factors influence the emergence and behaviour of crop pests and diseases. They will use a systems approach that incorporates these new predictors along with historical data and couples them with an artificial intelligence component that learns from ground observations recorded using smartphones to improve accuracy. They will combine their existing agricultural intelligence platform and smartphone application with their prototype predictive model and test their approach with maize and cassava crops on farms across seven different counties in Kenya. The platform will produce location-specific forecasts that can be acted upon immediately by farmers.
David Aanensen from the University of Oxford and the Wellcome Sanger Institute in the United Kingdom and Maria van Kerkhove of the World Health Organization in Switzerland will combine next generation DNA sequencing technology with a simple, web-based data collection, processing, and distribution platform to better track the global spread of deadly infectious diseases including Middle East Respiratory Syndrome (MERS-CoV). MERS - also known as camel flu - is a viral disease that causes fever, cough, diarrhea, and shortness of breath, and is transmitted from camels to humans. One third of people diagnosed with the disease die. Next generation sequencing (NGS) technology allows rapid, inexpensive detection of pathogens as they spread. However, laboratories in different member states use different formats for sequencing data, and there is no mechanism for sharing it in real time. This limits the value of the technology for stopping outbreaks. To address this, they will establish routine sequencing protocols for both human and camel samples, and develop an interactive web platform on which the sequencing and epidemiological data can be shared. This will help develop more effective, real-time medical and non-medical interventions at local, national, and international levels. Once established, the protocols developed here may be applied to outbreaks of other diseases.
Achim Hoerauf of IMMP in Germany will apply artificial intelligence (AI) to speed the development of treatments for onchocerciasis, which is an infectious disease commonly known as River Blindness caused by a parasitic worm. The parasites are spread by affected blackflies, and the worm larvae accumulate in the skin and eyes, causing irritation and sometimes blindness. Nearly 21 million cases occur each year, and 99% of affected people live in Africa. The drug currently used for treatment kills only worm larvae, and studies are ongoing to identify more effective drugs that target adult worms. However, evaluating these drug candidates requires manual analysis using microscopy of samples of irritated skin from patients after treatment. This process is time consuming and slows drug development. To address this, they will use samples that have already been manually annotated to train an AI system to automatically analyze future samples to recognize worm body parts, gender, vitality, and stage of development. Once established, the AI system will be tested with samples from a new clinical trial - tissues from patients treated with the new drug will be analyzed in parallel by human and computer. Once optimized, the AI system will take over the analysis, and the much slower human analysis will only be needed as a quality control system.
Yingda Xie of Rutgers, The State University of NJ and JoAnne Flynn of the University of Pittsburgh, both in the U.S., will develop a non-invasive approach for testing candidate anti-tuberculosis compounds in animal models and patients using positron emission tomography-x-ray computed tomography (PET/CT). Tuberculosis (TB) is a leading cause of death in developing countries, and rates are sustained by the causative bacterium, Mycobacterium tuberculosis, developing resistance to current drugs. To circumvent this, new drugs are being designed to target human cells and proteins rather than those of the bacteria. To test these drugs, new tools are also needed to monitor TB in patients. 18 Fluorodeoxyglucose (FDG)-PET/CT is a non-invasive imaging tool that uses radioactively-labelled glucose to light up areas of metabolic activity in the body such as the lesions formed by M. tuberculosis and immune cells that play a critical role in infection. They have histopathological sections and cell and chemical data of TB lesions from non-human primate models and will use them to quantify the different lesions. Then, by using the available PET-CT scans of the lesions, they will search for quantitative signatures that can predict a specific type of lesion. The accuracy of these PET/CT signatures will be tested in a separate group of animals. Their study will reveal details of the TB immune response across different lesions, which could help design new treatments, and the signatures can be used to test the activity of new drug candidates in animal models and humans.
Alain Labrique of Johns Hopkins Bloomberg School of Public Health in the U.S. and Meghan Azad of the University of Manitoba in Canada will study the impact of prelacteals - fluids or solids given before breastfeeding is established - on the populations of bacteria in the newborn gut (the microbiome), and how it may affect development. Immediate and exclusive breastfeeding helps maintain healthy growth in infants and protects them against infections, which are also influenced by their gut microbiome. However, in Bangladesh and many other low-resource countries, it is common practice to give newborns ritual foods, like honey or sugar water, before breastfeeding begins, which may impede development. They hypothesize a link between prelacteal use and newborn development mediated by the gut microbiome. To test this, they will use an ongoing population-based study in rural Bangladesh and compare the types and amounts of bacteria in the gut using stool samples of 300 prelacteal-fed and exclusively breastfed infants at 7 days, 28 days and 3 months of life. They will also analyze the composition of the prelacteals being used, including the presence of any toxic contaminants, and of the breastmilk of the mothers, for correlating with any changes in gut microbial populations. The study will enable them to quantify the potentially negative impact of this widespread cultural practice, common to over a billion people across the Gangetic floodplain.
Eric Kaduru of KadAfrica Estate Limited and John Onekalit of the Kitgum Concerned Women's Association both in Uganda will provide a 12-month, integrated life skills and agricultural training program along with land and seedlings to young refugee women out of school in Uganda to begin their own sustainable passion fruit farming cooperatives. Uganda has accepted many refugees, but also has the world's youngest population and very high unemployment. As a result, particularly girls have very limited employment opportunities if they even manage to finish school, and instead often work in the sex industry or immediately get married. This in turn leads to increased teenage pregnancies and rates of HIV. They will provide a cooperative start-up kit including training in sustainable passion fruit farming, which has a guaranteed market, access to land through a community-based land lease model, and passion fruit seedlings. The girls will also be taught about finance, nutrition, and sexual and reproductive health. They will test their approach in two refugee camps with 180 adolescent girls between 14- and 22-years old who are out of school. The success of the project will be assessed in terms of the effect on poverty and health.
Ruth Müller of the Institute of Tropical Medicine in Belgium and Meghnath Dhimal of the Nepal Health Research Council will provide entomological training for health science students and medical professionals and increase community awareness of vector-borne diseases (VBDs) in Nepal to better equip the population to deal with disease outbreaks. VBDs like those caused by the dengue, zika, or chikungunya viruses cause more than 700,000 deaths annually, mostly in poor countries with limited public health resources and tropical climates. Climate change has expanded the affected areas as warmer temperatures facilitate survival of the insect vectors. They will establish the EntoCAP team to enhance entomological capacity to fight these diseases. The team will hold five-day workshops for 300 health science students and health care professionals on surveillance and control of vector populations, and monitoring of disease outbreaks. They will also increase community interest in VBDs by hosting science labs for children to teach them how to recognize mosquitoes at various developmental stages and understand the dangers of VBDs. In addition, they will begin building a reference collection using DNA barcoding technology to catalog insect vectors by species for studying biodiversity and microevolution of disease vectors.
Elena Levashina of the Max Planck Institute for Infection Biology in Germany and Kelly Lee of the University of Washington in the U.S. will use cryoelectron tomography to image the three-dimensional ultrastructure of a protein on the surface of the malaria-causing parasite Plasmodium falciparum to help design better vaccines. Malaria kills half a million people annually, but there are still no highly effective vaccines available. One of the parasite's coat proteins, CSP, is a prime target for vaccine development. However, not much is known about its natural structure on the live parasite, which is how inhibitory antibodies produced in response to a vaccine will be able to recognize and destroy it. One of the best ways to observe the natural structure of a protein at high resolution is to immobilize it in non-crystalline ice and image it under very low (< −150 °C) temperatures. They will develop protocols to isolate large numbers of highly pure parasites directly from mosquitoes and carefully cryopreserve them on grids to maintain their natural form and enable clearer imaging. They will also use this high-resolution imaging technique to study how antibody binding affects the parasite. Their results will help design new vaccines that can produce highly active, inhibitory antibodies.