Anna Casalme of Novelly in the U.S. will develop a mobile phone application that combines young adult fiction about social issues with learning tasks and international discussion forums to encourage young people to become global citizens and spark their interest in issues such as gender equality and health. Building on their existing program, they will design and develop the application with specific features, add one novel, and pilot test it, before refining the design and opening it to the public. After three months, they will evaluate their approach by collecting user data such as number of users, their reading progress, and participation in discussion groups.

Eric Dawson of Peace First Inc. in the U.S. will develop a digital platform that provides tools, online mentors, resources, and funding to help young people aged between 13 and 25 in the Middle East solve critical issues in their communities. Their Youth Challenge Platform approach has already shown initial success for over a hundred projects proposed and run by international youth in the U.S. They will adapt their platform for the Middle East by including different languages and tools, particularly to foster cross-cultural collaborations. They will partner with youth organizations in five to 10 Middle Eastern countries and recruit 50 teams of young people who are interested in solving problems related to the UN sustainable development goals. These teams will be supported through the platform to help them design and implement innovative solutions. Surveys and interviews will be used to evaluate the success of their approach in this region.

Lucy Kathuri-Ogola of Kenyatta University in Kenya will train young people to be outreach youth champions to support local smallholder farming households with low food security in Kenya by teaching them new agricultural practices and building financial and social support networks. They will develop a mobile phone application and training platform and test their approach in selected rural and urban areas in Kenya where many smallholder farming families rely heavily on food relief. Sixteen young people who are leaving university will be recruited as outreach youth champions and intensively trained over three weeks on best agricultural practices, and financial and support services such as farmer saving groups. The trained youths will then each go back into their own communities and work with ten households to improve overall social and economic status. They will use surveys to evaluate the effect of their approach on food security.

Romeo Rodriguez of World Possible in the U.S. will use their massive open online courses (MOOC) to provide teachers with advanced practical skills and tools such as inquiry, teamwork, and self-directed learning, to transform teaching and improve student performance in developing countries. The online course also works offline using their low-cost community hotspot. They will implement the courses over twelve months across 15 offline public middle schools in Guatemala and evaluate its impact on teaching methods and whether this can be enhanced by offering additional three-day in-person training. They will also partner with the Ministry of Education and a respected local university to create a digital certification to further motivate teachers to take the course.

Sara-Christine Dallain of iACT in the U.S. will train refugee men and women to become skilled and empowered teachers who deliver early childhood care and education to support the social-emotional, cognitive, and physical development of children in refugee camps. Over 11 million children have been forced to flee their homes, challenging their ability to reach their full potential. Many lack the tools needed to adapt to the uncertainty of their present and future. Their program, Little Ripples, is a refugee-led, culturally-inspired, and cost-effective early childhood education program. It provides training for teachers to incorporate skills of empathy, leadership, teamwork, and creative problem-solving when teaching pupils to create an environment that fosters peace, imagination, and connection-to-culture for refugee children. The curriculum has been developed by experts and is adaptable to different contexts, and the program can be led and expanded to other regions by the teachers themselves. They will implement and test their program in refugee communities in eastern Chad, Cameroon, and Greece to evaluate the impact on refugee children.

Yen Verhoeven of the Paragon Learning Research Group in the U.S. will create a digital platform for massive open online courses (MOOCs) and a supportive online community of professionals for kindergarten to sixth grade teachers to transform their teaching practices and bring STEM and 21^st century skills to their schools. MOOCs were developed as a means to provide free education to everyone. However, their content is typically restricted to videos and reading with little interactive learning, which is inadequate for teaching life skills such as critical thinking and creativity. And encouraging teachers to adopt new teaching practices requires additional professional support from peers and mentors. To address these issues, they will work with teachers and teaching experts to formulate a new MOOC design containing a variety of instructional resources and free professional development classes and develop a beta version of the online community platform. They will evaluate the course by teaching it to local K-6 teachers and gathering feedback to refine the content.

Hans Brunner of Value Spring Technology, Inc. in the U.S. will build and test an artificial intelligence (AI) tutor to teach the scientific method and critical thinking skills to individual students at their pace and level. All children learn differently but one-on-one lessons are often prohibitively expensive or unavailable. To address this, in collaboration with two non-profit teaching institutions, they will adapt their AI software for education, and build and train an AI tutor, Ali. Ali will be designed to produce natural sounding language to engage students in conversation involving open-ended questions and answers that stimulate critical thinking, which is based on the Socratic method. Students will be taught at their own pace and level of understanding, and Ali will be built to ensure each topic is fully understood before starting the next. They will engage teachers to test and critique their AI tutor approach and to evaluate its teaching performance.

Saurabh Agarwal of Deeper Learning Innovations Private Limited in India will build an interactive, digital teaching platform using advanced data analytics and artificial intelligence algorithms to enable teachers across the globe to more effectively teach life skills to every child. Teaching standards in developing countries suffer from limited access to quality content, restricted teaching methods for teachers, and a lack of ways to transfer knowledge and skills to other teachers and parents. Life skills such as problem solving and communication that are needed to address 21^st century challenges such as health, wellness, and gender equality are far better learned by experience and reflection, rather than reading and lectures. They will build the platform and incorporate life skills modules designed by learning experts and teachers containing multi-lingual and contextualized content for global access, a teacher's discussion forum, and a module designed by teachers to help parents support their child's education. The goal is to make the platform freely available and accessible to all teachers across the globe.

Ann Vinckier and colleagues at QIAGEN in the U.S. propose to further improve their commercially available small fluorescence tube scanner for its use at the point-of-care in developing countries, and also investigate probe-­based isothermal amplification technologies for the development of fast, sensitive, specific and robust detection of nucleic acids in point­-of-­care diagnostic tools.

Robert Moritz and colleagues at the Institute for Systems Biology and Seattle Biomed in the U.S. will use ultra­-sensitive targeted assay technology to identify, quantify, and validate a library of biomarker candidates specific to both active and latent TB infection. Moritz and his team hope to discover highly specific proteins that could help determine disease status at the point of care and inform appropriate treatment.

John Belisle of Colorado State University in the U.S. will assess the feasibility of using small molecules created by the metabolic processes of host or pathogen cells, as well as lipids and fatty acids produced by the TB bacterium, as biomarkers of active disease.

Karen Dobos of Colorado State University in the U.S., along with Jeff Schorey of the University of Notre Dame and their partners at the University of San Francisco, seek to identify and validate protein signatures on exosomes, which are small vesicles secreted by M. tuberculosis-­infected host cells, for use as biomarkers to diagnose TB. These protein signatures seem to be concentrated by exosomes in such a way that they could be used as highly sensitive indicators of disease in diagnostic tests.

David Anderson of the Macfarlane Burnet Institute in Australia will examine a unique aspect of the host antibody response that may better differentiate current and past tuberculosis infections. If successful, this approach could be readily incorporated in simple, disposable blood test formats that are currently used for diagnosis in resource-poor settings.

Robert M. Kennedy of the Vestaron Corporation in the U.S. will develop synthetic chemical mimics of selectively insecticidal natural peptides.

Barry Beaty of the Colorado State University in the U.S. will develop an innovative and robust, platform-­based approach for sustainable insecticidal control of Anopheline mosquitoes.

Luke Lee of the University of California, Berkeley in the U.S. proposes to develop a microfluidic sample preparation module using electrical and physical methods that will be compatible with different sample inputs and downstream analytical techniques to provide both plasma and cellular biomarkers for the parallel diagnoses of infectious diseases such as HIV, tuberculosis, and malaria. The device will not require external reagents, will have low power consumption, and can be operated on­-site with minimal training.

Robert (Bruce) Cary of Mesa Tech International, Inc. in the U.S. proposes to develop nucleic acid purification systems that use a novel configuration of lateral flow materials to bind and wash nucleic acids to yield amplification-­ready samples. These devices could provide purified samples from clinical specimens within minutes without user intervention, instrumentation, electricity or costly materials.

Donald Chickering and a team at Seventh Sense Biosystems in the U.S. are developing its Touch Activated Phlebotomy (TAP) platform to enable one­-step blood collection in a safe, painless, and convenient manner. The device uses an integrated system of microneedles and vacuum capture of a blood sample for downstream analysis. TAP has the potential to expand access to diagnostic testing into underserved and hard-­to-­sample populations, while also improving safety and ease of collection.

Ross Durland and colleagues at AM Biotechnologies, LLC in the U.S. propose to develop X-­aptamers for detecting and quantifying protein biomarkers for neglected diseases. X­-aptamers are modified nucleic acids that tightly bind to specific targets and remain stable at high temperature and humidity. AM Biotech will enhance its process for rapidly identifying X-­aptamers that will be integrated into a point­-of-­care platform for diagnosing many diseases.

Rebecca Richards-­Kortum and Tomasz Tkaczyk of Rice University in the U.S. propose to develop a plug­-and-­sense read-out and signal transduction (ROST) component for point­-of-­care devices that will be palm­-sized, producible for under $10, and with new interrogation units can be rearranged within the universal fixture to accommodate new sample platforms.

Axel Scherer of the California Institute of Technology in the U.S., along with collaborators at Dartmouth, will develop a prototype quantitative PCR (qPCR) amplification/detection component module that can rapidly detect a wide range of pathogens with low cost, low internal and outward complexity, low power consumption, a small size, and a rugged design.

Bananas are the major staple food in Uganda, where the average person consumes more than 1 kilogram of the fruit each day. Banana-based diets, however, are deficient in vitamin A and iron, as well as in vitamin E. A promising long-term solution to this problem may be to genetically modify crops, including bananas, so that they contain high levels of essential nutrients. Dr. Dale is leading a team of scientists in Australia, Uganda, and the United States who are attempting to genetically modify bananas raised in Uganda so that their content of vitamin A, vitamin E, and iron is equal to or exceeds the required daily allowance. Dale, Tushemereirwe (Grand Challenges in Global Health: 2005-2015 retrospective)

A subset of women who apparently are resistant to HIV infection may provide scientists with the genetic and immune system information they need to advance vaccine and drug development. Since 1985, investigators have tracked groups of commercial sex workers in Kenya who do not become infected with HIV despite repeatedly having sex without condoms. If investigators can understand what constitutes and results in protective immunity against HIV, they may be able to replicate it through vaccines. Dr. Plummer's team is conducting an exhaustive analysis of the immunologic and genetic factors that mediate HIV resistance in the women, with the goal of gaining a more complete understanding of what constitutes protective immunity against HIV infection.

Vaccines are urgently needed to slow the spread of HIV and hepatitis C virus (HCV), which together infect an estimated 240 million people, most of them in developing countries. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Deng and his colleagues are working to improve techniques for creating mouse models with immune systems and livers that are similar enough to humans to allow testing of potential HIV and HCV vaccines. The team is working to create chimerical mouse models with hematopoietic cells (HSCs) and hepatocytes differentiated from human embryonic stem (hES) cells.

To stop the spread of tuberculosis, scientists are working to develop methods that prevent new infections and also eliminate infection in the huge reservoir of people who already are infected with MTB. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent MTB from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr. Andersen’s is leading a collaborative team of international researchers who are studying Mycobacterium tuberculosis to identify the mechanisms that, in some people, allow it to escape natural immune system responses. The project's ultimate goal is to develop vaccines that target latent TB, either before or after an individual is infected.

Hepatitis C virus (HCV) is a major cause of liver diseases, including cirrhosis and liver cancer. Treatment for chronic hepatitis C is often out of financial reach for people in developing countries, and there is no vaccine against the virus. To prepare a human vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. Dr. Balling's team, partnering with Dr. Di Santo's group at the Institut Pasteur in France, is working toward the development of mice with livers and immune systems that are similar to those of humans. These animals might be used to test vaccines for HCV, and potentially, other human pathogens.

Although rice is a primary source of food for much of the world's population, it is a poor source of many essential micronutrients, as well as protein. As a result, widespread reliance on rice is the primary cause of micronutrient malnutrition throughout much of the developing world. Dr. Beyer is leading an international, collaborative effort called the ProVitaMinRice Consortium. The consortium's members are developing new varieties of rice with increased levels or bioavailability of pro-vitamin A, vitamin E, iron, and zinc as well improved protein quality and content. As their platform, the consortium's researchers are using Golden Rice, which has been genetically engineered to produce and accumulate pro-vitamin A in the grain, and are working with novel transgene-based technologies to enhance the availability of the target nutrients.

Dr. Shattock and collaborators in the U.K. and South Africa will attempt to develop an HIV vaccine that stimulates immunity to the virus in the lining of the vagina. The investigators hypothesize that an HIV vaccine will be most effective at the site where the virus enters the body. Innovative combinations of vaccine antigen formulas and delivery technologies will be used to develop a potentially potent and effective vaccine. The vaccine will be designed to be delivered via low-cost vaginal gels or via silicone rings that fit inside the vagina and can be self-administered.

The inability to ensure that newly introduced genes will become established within regional mosquito populations has been a major roadblock to the advancement of genetic strategies for vector control. Dr. Burt and his colleagues are investigating homing endonuclease genes (HEGs), so-called "parasitic" genes that can spread rapidly through mosquito populations even if they harm the host insect. This gives HEGs the potential to move newly introduced traits, such as sterility or inability to transmit disease, through a population quickly. The project's ultimate goal is to develop HEGs as a flexible, robust, powerful, and safe system to drive useful traits through populations of mosquitoes that transmit malaria. Burt (Grand Challenges in Global Health: 2005-2015 retrospective)

The current vaccine against bacterial pneumonia (pneumococcus) requires a regimen of four injections given at specific intervals. In developing countries, this not only complicates the vaccination process for health workers and children, but it also is a serious obstacle for families who must travel long distances to the nearest health clinic. Dr. Curtiss and his colleagues are working to develop new vaccines against bacterial pneumonia that require only a single dose, can be delivered orally, and are safe for newborns, infants, and people who are malnourished or whose immune systems are compromised.

To maintain stability and viability, most childhood vaccines must be kept cool – both heat and freezing can ruin them. That means many must be refrigerated at the correct temperature throughout transportation, storage, and delivery. This cold chain is difficult and costly to maintain, especially in developing countries. Dr. Gardner and his colleagues are adapting high-throughput formulation technology developed by TransForm Pharmaceuticals, Inc. that can quickly screen different formulations of vaccines to identify those that are most likely to be stable, safe, and effective. The team's initial work focuses on reducing refrigeration requirements for the existing live attenuated vaccine for measles, a freeze-dried vaccine that must be stored at between 2° and 8° Celsius and is very sensitive to heat and light once it is reconstituted.

In the developing world, infections in the respiratory and intestinal tracts are major causes of sickness and death, especially among children. Vaccine delivery systems that can target respiratory or intestinal mucosal tissue and stimulate immune response there have the potential to be particularly effective against these infections. Dr. Lo's project addresses two needs: the development of vaccine delivery systems that do not require needles and the design of systems that target specific tissues in the body. Using influenza vaccination as a model, Dr. Lo and his team are working to bind vaccine to specially designed molecules that target mucosal tissue.

Many serious infections, such as the measles virus, can enter the body through inhalation. Vaccine delivery systems that can target respiratory mucosal tissue and stimulate immune response there have the potential to be particularly effective against these types of infections. Collaborating with an international group that includes the Serum Institute of India (SII), the U.S. Centers for Disease Control and Prevention (CDC), the University of Colorado, and private companies, Dr. Sievers and his colleagues at Aktiv-Dry, LLC (AD) are developing a dry-powder version of the measles vaccine that can be inhaled through a disposable plastic device. Sievers (Grand Challenges in Global Health: 2005-2015 retrospective)

To develop new vaccines against some of the world's biggest killers, including HIV, malaria, and tuberculosis, scientists must be able to evaluate promising candidates. Some of the most promising potential vaccines, are made from weakened live versions of the infectious agent. As a result, they cannot be studied in human trials unless researchers can be confident that the weakened vaccines will be safe. Dr. Flavell and his colleagues are working to genetically engineer laboratory mice whose immune systems are similar enough to humans to permit testing of vaccines against diseases that disproportionately affect people in the developing world. Flavell (Grand Challenges in Global Health: 2005-2015 retrospective)

Dr. Steinman’s team is developing vaccines that stimulate the immune system’s dendritic cells, which are known to play an important role in stimulating protection against infectious diseases. One approach is to engineer vaccine antigens into monoclonal antibodies against receptors on the surface of dendritic cells. A secondary approach involves engineering genes for the antigens of interest into the yellow fever virus. The project will focus on creating experimental vaccines for a range of diseases, including HIV and malaria. If successful, this technology could identify a better way to create vaccines that stimulate multiple components of the body’s immune response, including those that have been difficult to target with existing vaccine approaches.

More than a million people die of malaria each year — most of them infants, young children, and pregnant women, and most of them in Africa. Although severe malaria has a high mortality rate, some children in areas where the disease is endemic might experience only one or two episodes of severe illness before they become resistant to further bouts of the disease. Dr. Duffy's team is attempting to identify the antibodies and other immunological responses that protect children from severe illness and death due to the malaria parasite Plasmodium falciparum, the most deadly of the four parasite species of human malaria.

Approaches to controlling disease-carrying insects might include inhibiting the development of virus in the mosquito or altering the insects' lifespan so that they die before they can transmit disease. A major challenge to this approach, however, is ensuring that such strategies are effective, safe, and socially and environmentally acceptable. Dr. James is leading an international team of scientists that is seeking to develop methods of controlling the transmission of dengue viruses using genetic techniques, including those that may block virus transmission by mosquitoes and reduce or eliminate populations of mosquitoes that transmit the virus.

Efforts to control the spread of malaria face serious challenges, including the parasite’s increased resistance to both medications and insecticides and environmental concerns about the use of traditional insecticides. Mosquitoes that spread malaria parasites use their sense of smell to find human hosts, most often by cueing in on the scent of human sweat and the carbon dioxide present in breath. Drs. Axel and Vosshall and their colleagues are seeking to develop a new generation of insect repellents that work by disrupting the olfactory system of the Anopheles mosquito, the primary vector in Africa. Axel, Vosshall (Grand Challenges in Global Health: 2005-2015 retrospective)

Poor nutrition is a major global health problem, contributing to half of the nearly 10 million deaths that occur each year in children younger than 5 and much of the death disease and suffering impacting sub-Saharan Africa. A starchy root crop called cassava is the major source of calories for more than 250 million Africans in this region, but cassava has the lowest protein-to-energy ratio of any staple crop. Dr. Sayre is leading a multidisciplinary team of scientists, brought together as BioCassava Plus, that is working to create nutritious cassava for sub-Saharan Africa. Team members are screening additional transgenic plants and expect that complimentary genetic strategies currently underway will soon yield plants that achieve their targeted levels of iron, zinc, and protein.

Dr. Baltimore’s team is exploring a new way of stimulating the immune system to fight infectious diseases, focusing on HIV. The premise of this project is that for some infections, including HIV, the immune system’s natural responses are inherently inadequate, and the traditional approach of using vaccines to stimulate and boost these responses is likely to be ineffective. As an alternative, Dr. Baltimore and his colleagues propose to "engineer immunity," that is, use genetic engineering methods to produce immune cells that will make specific antibodies to fight off infection. Baltimore (Grand Challenges in Global Health: 2005-2015 retrospective)

Each year, about a half-million women, 80 percent of them living in low-income countries, develop cancer of the cervix. The disease kills 250,000 women annually, and is the second leading cause of cancer deaths among women living in less developed countries. Nearly all cases of cervical cancer are caused by infection with human papillomavirus (HPV), the most common viral infection of the reproductive tract. Dr. Garcea's team is working to develop an inexpensive therapeutic vaccine against HPV that will not only protect people from developing new infections, but could potentially trigger an immune system response to cure those who are already infected.

In the developing world, lack of convenient and accurate tools that can detect and diagnose diseases and other health problems means that many health risks remain undetected or receive inappropriate treatment. Dr. Yager's team, in collaboration with research groups from private industry as well as the nonprofit sector, is working to develop a low­-cost, easy-­to-­use device that will rapidly test blood for a range of health problems prevalent in developing countries, such as bacterial infections, nutritional status, and HIV­-related illnesses.