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.

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.

Anthony Kolozetti of My School ROCKS in Canada will develop an educational music application for schools that combines collaborative technology with the universal medium of music to help young people succeed academically and acquire 21^st century skills such as mindfulness, stress management, resilience and empathy. Growing numbers of students are suffering from unhappiness at school, experiencing daily anxiety and stress. To address this, they will exploit the synergy between music, education, and mental wellness by creating a platform where students can easily write, record, mix, and share curriculum-based music projects. They will consult with professionals working on neuroplasticity to identify lesson types that have optimal effects on the brain. They will then bring together artists, mental health professionals, technology experts, students, parents, and educators to identify goals and use them to create lesson plans and resources for social emotional learning, song-writing and artistic performance, that can be digitalized in an application. They will also integrate modules that enable students to create their own music-based projects, which can become school-wide performances, without the need for trained music teachers, to showcase songwriting, musicianship, and collaboration. They will pilot test the project over five months in diverse school communities and measure its academic and social impact using surveys and interviews.

Hira Zainab of Knowledge Platform Limited in Pakistan will develop a 'Birds and Bees' program to enable teachers and students from underprivileged schools in Islamabad, Pakistan to design and build bird feeders and bee colonies in order to nurture birds and bees and to market honey. Pakistan is home to over 700 species of birds and fauna that can support substantially increased national honey production. They will recruit pilot schools and work together with the teachers and students to research the local bird species in order to design effective bird feeders. They will also design online and printed material that teaches students about nature and science and how to nurture and attract birds and bees and extract and market honey under a social enterprise brand. They will also produce videos to build a community of nature lovers and problem solvers to help teach others about the program.

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. Hill and his colleagues are exploring a novel approach to enhancing the ability of plasmid DNA, pox, or adenoviral vectored vaccines to stimulate strong immune responses. Building on recent advances in understanding of pattern recognition molecules as well as intracellular signaling pathways, investigators are working to add intracellular adjuvants (molecular signals that have the potential to enhance immunogenicity) to the vaccine vectors. Also being explored is the effect of adding molecules designed to inhibit regulatory pathways that may be limiting protective immune response. The team is focusing on improving vectors for vaccines against malaria, HIV, and tuberculosis. Hill (Grand Challenges in Global Health: 2005-2015 retrospective)

Due to differences in their immune systems, individuals respond to malaria in different ways. While some die, others survive, and still others are infected without becoming ill. Understanding how and why some people naturally resist malaria may help lead to the development of an effective vaccine against the disease. Dr. Kwiatkowski is leading the Malaria Genomic Epidemiology Network, or MalariaGEN, an international partnership of malaria research groups. MalariaGEN partners in 20 countries, including in 14 countries where malaria is endemic, are combining genomic technology with large-scale epidemiological analyses to identify mechanisms of protective immunity against malaria in humans. Their ultimate goal is to guide the development of tools and markers to facilitate the design and testing of vaccines against malaria. Kwiatkowski (Grand Challenges in Global Health: 2005-2015 retrospective)

An estimated 2 billion individuals - a third of the world's population - have been exposed to Mycobacterium tuberculosis (MTB) and carry the infection in its latent form, retaining a lifelong risk of developing TB disease. Programs to control tuberculosis now focus on childhood vaccination and treatment for people with active disease. Reversing TB's spread, however, requires an intervention that will prevent disease in those who are already infected. The lack of knowledge about the biology of latent TB infection stands in the way of the development of such an intervention. Dr. Young is leading an international team of researchers from the U.K., U.S., Singapore, Korea, and Mexico that is attempting to further elucidate the fundamental biology of latency and use this knowledge to develop drugs against latent TB. Young (Grand Challenges in Global Health: 2005-2015 retrospective)

To maintain stability and viability, most childhood vaccines must be kept cool - both heat and freezing can ruin them. That means they 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. Sonenshein and his team are working to create childhood vaccines for diphtheria, tetanus, and pertussis (the DTP combination vaccine), and rotavirus-related diarrhea that can withstand a wide range of temperatures without refrigeration by encapsulating them in harmless bacterial spores that are naturally heat-resistant.

To maintain stability and viability, most childhood vaccines must be kept cool – both heat and freezing can ruin them. Drs. Sarkari and Coeshott and their colleagues are working to identify Pluronic polymer-based formulations that stabilize vaccines from -10°C to 45°C. Their aim is to develop vaccines that are resistant to freezing and form protective matrices at elevated temperatures. Investigators are evaluating formulations based on Pluronic F127 using vaccines for measles and hepatitis B.

Vaccines that can be delivered without needles have the potential to be simpler to administer and less prone to spreading infection. Dr. Baker's team is developing a new way of preparing vaccines so that they can be given as nasal drops. These nanoemulsion-based vaccines use non-toxic lipid droplets less than 200 nanometers in diameter that are absorbed through the mucosal surfaces of the nostrils. They can be easily produced using an extrusion process available worldwide and are antimicrobial, eliminating the need for preservatives or refrigeration. The team is performing proof-of-concept, feasibility, and toxicology studies for a nanoemulsion-based vaccine for hepatitis B surface antigen. Baker (Grand Challenges in Global Health: 2005-2015 retrospective)

Vaccine delivery systems that target specific areas of the body have the potential to be especially effective against some types of infection. For example, inhaled vaccines may better guard against respiratory diseases, such as tuberculosis, and those that commonly infect the tissues of the nose and throat, such as diphtheria. Dr. Edwards is leading a multidisciplinary team using materials science technologies combined with infectious disease, device, and toxicology expertise to reformulate tuberculosis and diphtheria vaccines into aerosol sprays that can be inhaled. The team's ultimate objective is to develop a cell-based BCG vaccine for tuberculosis and a protein antigen CRM 197 vaccine for diphtheria in the form of novel porous nanoparticle aggregate (PNAP) aerosols.

Attenuated vaccines, composed of weakened organisms incapable of causing disease, provide prolonged exposure to antigens and have proven effective against several viral or bacterial diseases. Dr. Kappe's team is attempting to extend this concept to a malaria vaccine. In the case of malaria, disease develops when the malaria sporozoite – the form of the parasite that is transmitted from mosquitoes to humans – enters the bloodstream and moves to the liver. There, it grows and divides into thousands of parasites that invade and destroy red blood cells, causing disease. Dr. Kappe's team is working toward development of a malaria vaccine using a malaria sporozoite that has been weakened by gene deletion to stimulate immune response. Kappe (Grand Challenges in Global Health: 2005-2015 retrospective)

Dr. Shaw is leading a consortium of investigators from clinical and laboratory research sites in Africa, the Caribbean, and the United States. They are conducting a comprehensive, integrated analysis of humoral and cellular responses to HIV-1 in people in early and acute stages of infection. Investigators are basing their work on the hypothesis that HIV-1 leads to chronic, persistent infection rather than a rapidly lethal disease because elements of the human immune system partially constrain viral replication over long periods. Ultimately, the project's goal is to contribute to the development of vaccines for HIV and AIDS through better understanding of natural immune response to the virus. Shaw (Grand Challenges in Global Health: 2005-2015 retrospective)

Dr. Fraser's team is working to develop and test new approaches to suppressing the replication of dengue virus in the cells of its primary vector, Aedes aegypti mosquitoes. The team is using genetic strategies to introduce a molecular mechanism that uses the dengue virus' own genetic make-up to initiate a process that results in the death of infected cells in the mosquitoes, limiting their ability to transmit disease. In addition, investigators are working on tools to enhance the application of this and other genetic strategies in mosquitoes.

Mosquitoes that spread malaria parasites use their sense of smell to find human hosts. Dr. Zwiebel is leading an international consortium of investigators that seeks to understand and ultimately interfere with the molecular basis of the insects' sense of smell. Their work seeks to develop safe, effective and low-cost products that would either repel mosquitoes or attract them to traps. Zwiebel (Grand Challenges in Global Health: 2005-2015 retrospective)

The malaria parasites’ increased resistance to both medications and insecticides and environmental concerns about the use of traditional insecticides pose major challenges to decreasing the rate and breadth of infection. Dr. Bloomquist and his colleagues are using advanced molecular modeling and a novel chemical synthesis method called "click chemistry" in an effort to produce insecticides specifically targeted to the primary malaria vector mosquitoes, Anopheles gambiae. The insecticides would work by inhibiting the essential enzyme acetylcholinesterase (AChE) in mosquitoes. They could be used as a potentially safer and more effective alternative to existing insecticides used in treating bed nets.

More than 300 million people in arid and semi-arid regions of Africa rely on sorghum as their primary source of food. The grain is one of the few crops that grow well in arid climates, but it is deficient in most essential nutrients and is difficult to digest. The African Bio-fortified Sorghum (ABS) Project, a consortium of nine institutions led by Africa Harvest Biotech Foundation International, is working to develop new varieties of sorghum that are easier to digest and contain higher levels of vitamins A and E, iron, zinc, and the essential amino acids lysine, threonine, and tryptophan.

People infected with many serious illnesses, including tuberculosis and hepatitis C, may show no symptoms of disease for long periods of time. These inactive, or "latent," infections, however, can develop into active disease without warning, and also can be passed on to others. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent them from causing disease have the potential to significantly reduce illness, death, and disease transmission. Dr. Ahmed and his team are working to create safe and effective immunological therapies for chronic hepatitis C infection and other viral infections such as HIV by developing methods to reactivate “exhausted” immune cells that are thought be unable to clear the infection.

In the developing world, major gaps in methods and technologies to measure health status make it difficult to address inequities in health through changes in policy. Dr. Murray is leading an international team of investigators that is working to develop new technologies and methods for assessing health status in the developing world. Combining epidemiology, biomedical research, and population health assessment, the team hopes to produce new measurement tools that are science-based, standardized, and applicable to different resource-poor settings.