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.

Challenges

<h2>Opportunity:</h2><p>Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems.* Synthetic biology is characterized by a bottoms-up approach to designing biological systems for a specific purpose. Synthesis offers opportunities for achieving goals that observation and analysis do not: A synthetic goal forces science to encounter and solve problems that are not easily encountered through analysis, driving the creation of new solutions. The power of synthesis is well illustrated in chemistry, which has long had synthetic tools; biology has more recently developed such tools, synthesizing parts of living systems to test new ideas and create novel products.</p><ul><li><a href="http://www.synberc.org/content/articles/what-synthetic-biology" target="_blank" title="">http://www.synberc.org/content/articles/what-synthetic-biology</a>&nbsp;</li></ul><h2>What We’re Looking For:</h2><p>Synthetic biology techniques may offer valuable alternatives to standard approaches for a variety of human health applications including vaccine and drug creation, diagnostics, or combinations of interventions within a single biological system. The goal of this topic is to examine the potential for synthetic biology to contribute novel and radical approaches to generating new global health solutions. We wish to encourage researchers to harness these emerging tools for the goals of global health, and to support innovation in this emerging field that can be brought to bear on the needs of the developing world.</p><p>To be considered, proposals must closely align with one or more of the foundation’s Global Health priority areas: malaria, HIV, tuberculosis, pneumonia, enteric disease &amp; diarrhea, maternal neonatal &amp; child health, nutrition, polio, and/or family planning. See&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx&nbsp;</a>for information about the foundation’s strategies in our priority Global Health areas.</p><p>Consideration should be given to potential safety concerns; in particular, preventative interventions such as vaccines for global infectious diseases have a high safety bar. Applicants should also anticipate downstream delivery challenges inherent to the proposed idea (e.g., ensuring that an intervention reaches and enters the relevant tissues or cells in a patient) and, where possible, briefly suggest potential approaches to overcoming these challenges and/or factors mitigating the associated risks.</p><h3>A few of the many specific examples to be considered include:</h3><ul><li>Develop a novel intervention to prevent infectious disease using chemicals, materials or organisms engineered via synthetic biology approaches;</li><li>Biofabricate chemicals or materials to improve the efficacy of disease treatment, or to increase the chemical diversity available for new drug discovery/development;</li><li>Create a diagnostic biosensor&nbsp;for a global health indication using genetic circuitry or other approaches for stimulus and response induction;</li><li>Build a synthetic instance of a biological system to accelerate development of global health interventions (e.g. a predictive model for preclinical drug or vaccine testing;</li><li>Build a synthetic instance of a biological system to test and further our understanding of that system, addressing a critical knowledge gap in global health (e.g. a synthetic model of disease pathogenesis).</li></ul><h3>We will not consider funding for:</h3><ul><li>Potential solutions not aligned with the Gates Foundation’s Global Health priority areas and strategies listed above (see&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx</a>);</li><li>Therapeutic interventions in areas other than malaria or TB;</li><li>Approaches that present unacceptable downstream safety risks, e.g., as a barrier to product development;<br>Proposals that do not employ a synthetic biology approach, mindset or toolkit;</li><li>Research intended to expand or improve the basic tools, components or processes of synthetic biology, without a direct link to generating novel global health solutions;</li><li>Basic research without a clear objective to solve a global health problem, either the creation of a novel product / solution OR addressing a critical global health knowledge gap.</li></ul>

Grand Challenges Explorations

Apply Synthetic Biology to Global Health Challenges (Round 8)

<h2>Background:</h2><p>Immunization is one of the world’s most cost-effective health interventions. However, each year approximately 25 million infants are not fully vaccinated, and at least 2.4 million children die from vaccine-preventable diseases.</p><p>Since immunization programs were launched in low- and middle-income countries worldwide in the mid-1970s, most countries have been using the same standard package of six vaccines—measles, tetanus, diphtheria, whooping cough (pertussis), tuberculosis, and polio—in their national immunization schedule. In the last decade, however, as the public health impact of vaccines has become increasingly clear, interest in and funding for new vaccine development and delivery has surged. Throughout the next decade, low- and middle-income countries will have opportunities to introduce many new lifesaving vaccines into their standard immunization programs—in some cases doubling the number of vaccines offered in their programs within ten years.</p><p>The cost of traditional vaccines such as measles, diphtheria-tetanus-pertussis, and polio is low – often between $0.10 USD to $0.25 USD per dose. Due to both the investments made to discover and develop them, and because some of them are complex to manufacture, the cost of newer vaccines is significantly higher, ranging from $1.00 USD up to $15.00 USD.&nbsp; These increasing costs are driving the need to modify vaccine presentations.</p><p>With the introduction of these new vaccines, countries are facing new challenges—both in delivering these vaccines and in ensuring immunization programs reach new target populations. In 2010, a quarter of a million doses of pentavalent vaccine, costing nearly $1M USD, expired in one country’s central store because the system charged with delivering these vaccines was not yet ready to manage it. Another country was forced to delay its plans to introduce new vaccines because adding the new vaccine into the immunization program required a nine-fold expansion of the national storage system. Hence, low- and middle-income countries must find new ways to improve the logistics of national immunization programs to address the increasing burden facing their supply systems.</p><h2>Roadblock:</h2><p>Some of the key challenges facing immunization logistics and supply systems in low- and-middle income countries are as follows:</p><ul><li>New vaccines present multiple challenges to the immunization supply systems of low- and middle-income countries; some of new vaccines can occupy more cold chain space, may be more complex to prepare for administration, and may have a thermostability profile which is not suited to the challenging environment of low- and middle-income countries.</li><li>Current immunization supply systems were designed many years ago. As a result, they are often inefficient and operate in complete isolation from the supply systems of other health interventions and/or from the private sector. Furthermore, there is no mechanism in place to continuously monitor the performance of these systems in order to guide necessary adjustments and improvements.</li><li>Manufacturers and donors and to a certain extent countries themselves do not focus on the environmental impact of energy, materials, and processes used in the immunization supply system from the international to local levels.</li><li>Current information systems designs do not incorporate advances in technology that could help guide immunization program managers to plan and execute program strategies, thus ensuring that adequate quantities of vaccines, in the right format, are available to meet demand.</li><li>Current human resource policies do not guarantee that adequate numbers of competent, motivated, and empowered personnel are available at all levels to overcome existing and emerging immunization supply challenges within low- and middle-income countries.</li><li>In spite of the success of immunization programs, one in five children still does not have access to basic vaccines.</li></ul><h2>What we are looking for:</h2><p>This topic aims to generate novel approaches to optimizing the performance of immunization logistics and supply systems in low-resource settings. Applicants are encouraged to re-examine the systems trusted with delivering vaccines and design innovative solutions to optimize the performance of these systems, both today and in the future. We seek proposals that are responsive to the topic that are daring in premise and clearly different from the approaches currently under investigation or employed. The solutions submitted to this topic must be focused on the operational aspects of immunization systems in countries, and must have the potential to be scaled up or reproduced in multiple settings.</p><p>Proposals must provide a strong rationale for the work proposed, demonstrating a clear understanding of country context and needs, present a defined hypothesis, and an associated plan for how the idea would be tested or validated. Proposed ideas must ultimately be translatable to practical interventions accessible in resource-limited settings.</p><h3>We encourage applicants to address one of more of these gap areas:</h3><ol><li><em><strong>Vaccine characteristic prioritization</strong></em><ul><li>Mechanisms and tools that enable countries to assess the systems costs and benefits of specific types of vaccine product presentations and formulation, rather than product price alone, in order to inform their vaccine purchase decisions and optimize their relevance to their immunization strategies.</li></ul></li><li><em><strong>Supply system design</strong></em><ul><li>Innovative solutions that would allow health workers to easily increase quantity and volume of vaccines to reach remote or hard-to-reach areas.</li><li>Prove whether efficiency gains can be achieved through specific synergies between the supply systems of immunization programs and those of other health interventions or from the private sector.</li></ul></li><li><em><strong>Environmental impact</strong></em><ul><li>Tools and methodologies that incorporate the environmental, health and economic impact when making supply system design choices and selecting new technologies.</li><li>Incorporating global location information software tools to optimize logistics transport legs, delivery routes and reduce environmental impact of the programs.</li></ul></li><li><em><strong>Information Systems</strong></em><ul><li>Logistics management information systems that enable access to/ use of reliable and timely information at all levels of the supply chain (including the district and health post levels), for at least two health products (one of which must be vaccines).</li><li>Demonstrate the benefits of low-cost purpose-built devices (i.e. the point-of-sales equipment used in the for-profit world for barcode reading), for use in low-income settings to meet basic logistics management data requirements.</li></ul></li><li><em><strong>Human Resources</strong></em><ul><li>Development of innovative incentive programs to improve the performance of supply chain /logistics staff in low-income settings.</li></ul></li><li><em><strong>Vaccination acceptance</strong></em><ul><li>Innovative, affordable and sustainable approaches to increase the understanding, reach and public acceptance of immunization.</li></ul></li></ol><h3>We will not consider proposals for the following:</h3><ul><li>Proposals that do not directly address at least one of the areas of interest described above;</li><li>Proposals without a clearly-articulated objective or an objective that cannot be easily assessed for quality, efficiency and/or effectiveness;</li><li>Preclinical or clinical research: proposals for vaccine administration or delivery devices; proposals aimed at improving vaccine stability or formulation; proposals involving animal models or human subjects in clinical trials;</li><li>Approaches that represent incremental improvements to current activities or conventional solutions;</li><li>Approaches that are not applicable in low- and middle-income country settings;</li><li>New solutions that do not have the potential to be used widely or scaled-up;</li><li>Proposals that do not describe or outline the innovation’s down-stream effects on the supply system;</li><li>Proposals that can only be applied to individual manufacturers' products or specific product improvement initiatives.</li></ul><h3>For more information please consult the following links:</h3><ul><li><a href="http://www.path.org/publications/detail.php?i=1964" target="_blank">A vision for immunization systems in 2020: progress and gaps</a></li><li><a href="http://www.technet21.org/index.php/documents/80-logistics-and-programmatic-issues-related-to-new-vaccine-introduction/view-category.html" target="_blank">Challenges facing immunization systems in low and middle income countries</a></li><li><a href="http://www.who.int/immunization_delivery/optimize/" target="_blank">Optimize-immunization logistics and technologies for tomorrow</a></li></ul>

Design New Approaches to Optimize Immunization Systems (Round 8)

<h2>Opportunity:</h2><p>Our Global Health Program aims to create and improve preventative, diagnostic, and therapeutic interventions for infectious diseases and conditions affecting maternal, neonatal, child health and nutrition. We do this in three primary ways: 1) by identifying and filling gaps in knowledge that limit our progress on the critical path to health solutions; 2) by creating new technology platforms that can accelerate research in support of our goals or enable products suited to resource-poor settings; and 3) by investing in transformative ideas to help solve tough global health challenges. All of our investments are driven by the need to develop and apply solutions that can be deployed, accepted, and sustained in the developing world.&nbsp;</p><h2>What We’re Looking For:</h2><p>This topic seeks to complement the other, more specific Round 8 topics through the identification of new technology platforms, which can be translated into safe, effective, affordable and widely utilized interventions applicable to the following Global Health priority areas: malaria, HIV, tuberculosis, pneumonia, enteric disease &amp; diarrhea, polio, maternal and neonatal health, and/or family planning. Please note that if your idea responds to one of the more specific Round 8 topics, then you should apply under that topic. For more specific information about the foundation’s strategies in the priority Global Health areas, see:&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx</a></p><p>To be considered, ideas must constitute revolutionary rather than incremental improvements in health solutions, and any proposed technologies must be low cost. We define low cost as interventions targeted for populations with individuals living on less than $1 per day, deliverable, and scalable in low- and middle-income countries. Proposals must (i) have a testable hypothesis, (ii) include an associated plan for how the idea would be tested or validated, and (iii) yield interpretable and unambiguous data in Phase I, in order to be considered for Phase II funding.</p><h3>We encourage applicants to take one or more of the following approaches:</h3><ul><li>Intersections between any of the&nbsp;<a href="https://gcgh.grandchallenges.org/challenges/JTdCJTIyc29ydCUyMiUzQSUyMmRlc2NlbmRpbmclMjIlMkMlMjJzb3J0RmllbGQlMjIlM0ElMjJkYXRlJTIyJTJDJTIybnVtYmVyUGVyUGFnZSUyMiUzQTEwJTJDJTIycGFnZU51bWJlciUyMiUzQTAlN0Q=/JTdCJTIyeWVhcnMlMjIlM0ElNUIlMjIyMDA4JTIyJTJDJTIyMjAwOSUyMiUyQyUyMjIwMTAlMjIlMkMlMjIyMDExJTIyJTVEJTJDJTIyY2hhbGxlbmdlcyUyMiUzQSU1QiU1RCUyQyUyMnRlcm1zJTIyJTNBJTVCJTVEJTJDJTIyaW5pdGlhdGl2ZXMlMjIlM0ElNUIlMjI5NTk4MGE1Yy1jYjQ5LTQzMjctYjYwOS04NzU5MWVhMjJhMTElMjIlNUQlMkMlMjJsb2NhdGlvbnMlMjIlM0ElNUIlNUQlN0Q=">past Grand Challenges Exploration topics&nbsp;</a>(e.g., nutrition for vaccine efficacy; new ways to induce mucosal immunity to protect neonates);</li><li>Applying existent knowledge or technologies from developed world funding priorities towards new applications focused on our Global Health priorities;</li><li>Cross-disciplinary approaches that engage technical disciplines which are less represented in the global health arena.</li></ul><h3>We will not consider funding for:</h3><ul><li>Ideas or solutions not aligned with the Gates Foundation’s Global Health priority areas and strategies listed above (see&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx</a>);</li><li>Ideas without a clearly-articulated and testable hypothesis;</li><li>Approaches that represent incremental improvements to conventional solutions (e.g., research of current methods for vaccine discovery, development and delivery intended to expand, improve or integrate existing technologies or tools);</li><li>Basic research without a clear objective to solve a global health problem;</li><li>Variations on conventional small molecule and biologic therapeutic approaches (such as those focused on screening for new chemical entities, assays for validation, or tests of drug efficacy) that would yield drug treatment approaches in areas other than malaria or tuberculosis;</li><li>Solely behavioral change / educational initiatives (e.g., training programs, scholarships, education programs);</li><li>Solely infrastructure or capacity-building initiatives;</li><li>Approaches that present unacceptable downstream safety risks (e.g., as a barrier to product development);</li><li>Research that exclusively addresses other Round 8 topics (e.g., proposals that employ synthetic biology techniques, address nutrition for children between the ages of &lt; 9 months to 24 months, or seek to improve immunization supply systems).</li></ul>

Explore New Solutions for Global Health Priority Areas (Round 8)

<h2>Roadblock:</h2><p>Poor nutrition in the period from conception to 24 months after birth contributes to 35% of deaths of children &lt; 5 years of age, mainly due to increased mortality from infectious disease (The Lancet’s Maternal and Child Undernutrition Series, 2008). For children who survive, the effects of early undernutrition are long-lasting and largely irreversible and include a substantially higher risk of cognitive impairment and adult-onset chronic disease.</p><p>A key marker of poor nutrition is unhealthy growth, characteristics of which include intrauterine growth restriction (low birth weight for babies not born prematurely), and wasting (low weight for height) and stunting (low height for age) after birth. Underweight children can be wasted, stunted, or both. Better health outcomes are associated with nutritional strategies that distinguish between these cases, and rather than broadly increasing food energy intake, take a more precise approach, focusing on diet quality and targeting improvements in lean body mass and linear growth.</p><p>While it is imperative to develop new ways to promote healthy fetal and postnatal growth, there are unanswered scientific questions which hamper progress. For instance, the causes of stunting and intrauterine growth restriction and their links with other health outcomes are not fully understood. Furthermore, the molecular basis for nutritional deficiencies and their functional effects on tissues and organs remain unclear. Also unclear are the details of the critical role played by the human gut and its associated microbiota in both nutrition and immunity in infants and children.</p><h2>What We’re Looking For:</h2><p>The goal of this topic is to solicit new scientific understanding and new science-based preventative and therapeutic approaches to improve nutrition and promote the healthy growth and development of infants and young children. We strongly encourage investigating the mechanisms of action of nutritional deficiencies and interventions, since this will provide the basis for new strategies to promote healthy growth and will facilitate developing tests to measure nutritional status and to measure treatment outcomes, including discriminating responders from non-responders in population studies.</p><p>When practiced optimally, breastfeeding is one of the most effective available methods to promote child health and survival. Thus, while we include nutritional supplements and complementary foods among the potential interventions, proposed approaches should not interfere with or detract from immediate breastfeeding after birth and exclusive breastfeeding for six months thereafter when the infant only receives breast milk without any additional food or drink, not even water.</p><h3>We seek proposals that:</h3><ul><li>Target healthy growth specifically, rather than focus on broadly increasing food energy intake;</li><li>Are applicable to improving nutrition outcomes during the critical developmental period from conception to 24 months, since these approaches have a chance of preventing causes of newborn and childhood death as well as&nbsp; long-term adverse developmental and health effects;</li><li>Are "off the beaten track," daring in premise, and clearly differentiated from approaches currently being developed or employed; and</li><li>Have a testable hypothesis, include an associated plan for how the idea would be tested or validated, and yield interpretable and unambiguous data in Phase I so as to increase the chance of consideration for Phase II funding.</li></ul><h3>A few of the many options we will consider include:</h3><ul><li>Growth-promoting substances based on a new understanding of beneficial aspects of breast milk;</li><li>Approaches to enhance nutrient uptake or utilization based on the biology of the gut microbiota;</li><li>Approaches based on knowledge from veterinary science or animal husbandry;</li><li>Approaches that investigate as a secondary aim the role of nutrition in improving immunity and oral vaccine efficacy;</li><li>Approaches based on new models for studying environmental enteropathy and the interrelationship of nutrition, immune function, and infection at the level of the gut and its associated microbiota;</li><li>Approaches to promote healthy growth that are focused on developmental outcomes;</li><li>Approaches targeting maternal nutrition to stimulate optimal fetal and newborn health;</li><li>Use of new technologies to identify biomarkers of nutritional deficiencies and intervention outcomes;</li><li>Tests for healthy growth beyond those based on height or weight;</li><li>Investigation of the mechanisms of action by which nutrition improves development;</li><li>Better definition of stunting and wasting, and of their causes and functional effects.</li></ul><h3>We will not consider funding for:</h3><ul><li>Approaches that detract from beneficial practices, such as immediate and exclusive breastfeeding for the first six months after birth;</li><li>Approaches that are exclusively social or behavioral, such as education or training programs;</li><li>Approaches that are not applicable to the developing world setting;</li><li>Approaches targeting overnutrition or obesity;</li><li>Approaches targeting subpopulations with specific health conditions, such as diabetes;</li><li>Approaches that indirectly and broadly&nbsp;affect nutrient intake and assimilation, such as prevention and treatment of infection, sanitation approaches, and actions to increase income; and</li><li>Approaches already in a mature phase of clinical testing or product development.</li></ul>

Explore Nutrition for Healthy Growth of Infants and Children (Round 8)

<h2>The Context:</h2>

<p>Biotic stresses such as viruses, fungi, bacteria, weeds, insects and other pests and pathogens are a major constraint to agricultural productivity from fields to markets in the developing world. With few resources to combat or prevent infection and infestation, people farming small plots of land in developing countries are most vulnerable to these stresses and can experience devastating crop losses.</p>

<p>Currently, most crop protection strategies involve genetic improvement of plants to resist pests and pathogens and/or the application of chemical deterrents. In areas of high disease pressure, like tropical sub-Saharan Africa, new crop varieties that are released with single sources of genetic resistance are frequently overcome either before or soon after poor farmers gain access to the improved varieties. Although some farmers do apply chemical herbicides and pesticides, access is not always accompanied with training, which results in ineffective and unsafe use.</p>

<p>Pests and pathogens that affect crop plants after harvest can be equally difficult for smallholder farmers to combat. Post-harvest losses mean surplus crops do not reach market, affecting the livelihoods of farming families, and too often these families are left with no other option than to eat contaminated stored food. These constraints impact the food security of these farming families as well as the communities and countries in which they live.&nbsp;</p>

<h2>The Challenge:</h2>

<p>The aim of this topic is to solicit transformative solutions to the pest and pathogen pressures faced by smallholder farmers in developing countries. We encourage researchers and entrepreneurs to harness the emerging information and tools in biology and engineering for the goals of agricultural development, to generate ideas that will revolutionize current approaches to crop protection by focusing on the plant, the pests, pathogens, weeds, and/or their interactions.</p>

<p>To be considered, proposals must closely align with the goals of the foundation’s&nbsp;<a href="http://www.gatesfoundation.org/agriculturaldevelopment/Pages/default.aspx" target="_blank" title="">Agricultural Development&nbsp;</a>team. As such, we are looking for ideas that will:</p>

<ul>
	<li>Substantially increase the sustainable productivity of smallholder farmers in developing countries within the next 10-20 years;</li>
	<li>Have potential applicability to one or more of the following crops: maize, wheat, rice, millet, sorghum, cassava, sweet potatoes, yams, beans, cowpeas, chickpeas, and groundnuts;&nbsp;</li>
	<li>Target a specific or set of specific biotic stresses.</li>
</ul>

<h3>&nbsp;A few of the many possible examples to be considered include:</h3>

<ul>
	<li>Applications from outside the disciplines of biology, chemistry, and biochemistry;</li>
	<li>Biological control;</li>
	<li>Novel molecular or genetic solutions;</li>
	<li>Novel strategies in crop management;</li>
	<li>Biological and engineering solutions for post-harvest protection;</li>
	<li>New strategies for coupling broader environmental sustainability with crop protection;</li>
	<li>Integrated pest management systems;</li>
	<li>Genetic and biochemical approaches – if those approaches constitute a substantial improvement on current practices;</li>
	<li>Other applications not highlighted here.</li>
</ul>

<h3>We will not consider funding for:</h3>

<ul>
	<li>Ideas that are not directly relevant to developing countries;</li>
	<li>Ideas that are not applicable to the following crops: maize, wheat, rice, millet, sorghum, cassava, sweet potatoes, yams, beans, cowpeas, chickpeas, and groundnuts;</li>
	<li>Incremental improvements in crop protection strategies;</li>
	<li>Improvements to current regulated chemicals or the development of new chemical formulations that would be considered regulated chemicals;</li>
	<li>Maintenance crop breeding;</li>
	<li>Delivery models for seeds, chemicals, inputs, or other existing technologies;</li>
	<li>Proposals that focus solely on abiotic stresses (e.g., drought, heat, etc.).</li>
</ul>


Protect Crop Plants from Biotic Stresses from Field to Market (Round 8)

<p>Tsinghua University - Grand Challenges Explorations is a program launched by Tsinghua University in partnership with the Bill &amp; Melinda Gates Foundation. Aligned with the challenges under Grand Challenges Explorations, its goal is to foster innovative research with scientific rigor in global health research to enhance the diagnosis, treatment, and prevention of major infectious diseases, and save lives in China and other developing countries. The Tsinghua GCE program launched in 2011, with the first projects funded in 2012. Calls for proposals open yearly, and successful applicants have the opportunity to apply for Grand Challenges Explorations Phase II awards at the end of their Tsinghua GCE grants.</p>

China Tsinghua University - Grand Challenges Explorations

<h2>Opportunity:</h2>

<p>Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems.* Synthetic biology is characterized by a bottoms-up approach to designing biological systems for a specific purpose. Synthesis offers opportunities for achieving goals that observation and analysis do not: A synthetic goal forces science to encounter and solve problems that are not easily encountered through analysis, driving the creation of new solutions. The power of synthesis is well illustrated in chemistry, which has long had synthetic tools; biology has more recently developed such tools, synthesizing parts of living systems to test new ideas and create novel products.</p>

<ul>
	<li><a href="http://www.synberc.org/content/articles/what-synthetic-biology" target="_blank">http://www.synberc.org/content/articles/what-synthetic-biology</a></li>
</ul>

<h2>What We’re Looking For:</h2>

<p>Synthetic biology techniques may offer valuable alternatives to standard approaches for a variety of human health applications including vaccine and drug creation, diagnostics, or combinations of interventions within a single biological system. The goal of this topic is to examine the potential for synthetic biology to contribute novel and radical approaches to generating new global health solutions. We wish to encourage researchers to harness these emerging tools for the goals of global health, and to support innovation in this emerging field that can be brought to bear on the needs of the developing world.</p>

<p>To be considered, proposals must closely align with one or more of the foundation’s Global Health priority areas: malaria, HIV, tuberculosis, pneumonia, enteric disease &amp; diarrhea, maternal neonatal &amp; child health, nutrition, polio, and/or family planning. See&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx&nbsp;</a>for information about the foundation’s strategies in our priority Global Health areas. Consideration should be given to potential safety concerns; in particular, preventative interventions such as vaccines for global infectious diseases have a high safety bar.&nbsp;</p>

<h3>A few of the many specific examples to be considered include:</h3>

<ul>
	<li>Develop a novel intervention to prevent infectious disease using chemicals, materials or organisms engineered via synthetic biology approaches;</li>
	<li>Biofabricate chemicals or materials to improve the efficacy of disease treatment, or to increase the chemical diversity available for new drug discovery / development;</li>
	<li>Create a diagnostic biosensor&nbsp;&nbsp;for a global health indication using genetic circuitry or other approaches for stimulus and response induction;</li>
	<li>Build a synthetic instance of a biological system to accelerate development of global health interventions (e.g. a predictive model for preclinical drug or vaccine testing;</li>
	<li>Build a synthetic instance of a biological system to test and further our understanding of that system, addressing a critical knowledge gap in global health (e.g. a synthetic model of disease pathogenesis).</li>
</ul>

<h3>We will not consider funding for:</h3>

<ul>
	<li>Potential solutions not aligned with the Gates Foundation’s Global Health priority areas and strategies listed above (see&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank">http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx</a>);</li>
	<li>Drug treatment approaches in areas other than malaria or TB;</li>
	<li>Approaches that present unacceptable downstream safety risks, e.g., as a barrier to product development;</li>
	<li>Proposals that do not employ a synthetic biology approach, mindset or toolkit;</li>
	<li>Research intended to expand or improve the basic tools, components or processes of synthetic biology, without a direct link to generating novel global health solutions;</li>
	<li>Basic research without a clear objective to solve a global health problem, either the creation of a novel product / solution OR addressing a critical global health knowledge gap.</li>
</ul>


Apply Synthetic Biology to Global Health Challenges (Round 7)

<h2>Roadblock:</h2>

<p>Each year approximately 25 million infants do not receive the necessary immunizations, and at least 2.4 million children die from vaccine-preventable diseases—approximately 14 percent of deaths in children under 5.&nbsp;&nbsp;Millions more survive, but are left severely impaired. The long-term effects of these childhood illnesses limit the ability of those who survive to become educated, to work, or to care for themselves or others.</p>

<p>One of the major challenges of immunization programs in the developing world is maintaining robust year-to-year vaccination coverage for children.&nbsp;&nbsp;While there are many factors contributing to vaccine availability and distribution, cell phones and related technologies may be particularly useful for tracking which children have received which vaccinations, and efficiently connecting needy children with available vaccines.</p>

<p>At the same time, the UN predicts that cell-phone ownership will reach 5 billion in 2010, with most growth occurring in the developing world.&nbsp; This proliferation of cell phones and connectivity offers an unprecedented opportunity to access vast populations, including previously hard-to-reach populations in rural areas.&nbsp; Cell phones also provide previously unavailable capabilities in the developing world, including computational power, text and image displays, imaging, incentive structures, and standardized interfaces that can be leveraged to create powerful systems.</p>

<p>The effort to improve vaccine delivery has met with a number of challenges for which solutions are not readily available. The following have been identified in particular:</p>

<ul>
	<li>Positively identifying&nbsp;an individual infant/child for developing world vaccination programs.&nbsp;&nbsp;&nbsp;Knowing a child's identity is essential for recording&nbsp;the administration of a&nbsp;vaccination or for looking up the child's history if it's available.&nbsp; However, names and addresses are not consistently used and can be difficult to record, even in paper based systems.&nbsp; ID's printed on cards can get lost or destroyed.&nbsp; Due to rapid growth rates, robust biometric data for children are especially difficult to find and validate;</li>
	<li>Rapidly determining the immune status of an infant/child at the point of vaccination.&nbsp;&nbsp;Determining the immune status, including the natural and vaccine-related correlates of immunity in a rapid point-of-vaccination would aid in determining vaccine penetration and efficacy in target populations<strong>;</strong></li>
	<li>Connecting vaccine availability with target populations.&nbsp;&nbsp;Often, vaccinations are offered only for a short period, and need to serve an extended geographical area.&nbsp;&nbsp;As this can involve a great deal of travel and associated cost, ensuring that patients have timely and accurate information on where and when vaccinations are to be offered can increase participation, enhancing coverage and penetration.</li>
</ul>

<h2>What We’re Looking For:</h2>

<p>The goal of this topic is to solicit innovative approaches to address the roadblocks listed above.&nbsp; We seek proposals that may be "off the beaten track" and daring in premise, and are clearly differentiated from approaches currently being developed or employed.&nbsp; Proposals must (i) have a testable hypothesis, (ii) include an associated plan for how the idea would be tested or validated, and (iii) yield interpretable and unambiguous data in Phase I if they are to be considered for Phase II funding.</p>

<h3>A few of the many specific examples to be considered include:</h3>

<ul>
	<li>Systems that leverage cell phones to efficiently connect available vaccine with target infant/child populations;</li>
	<li>Biometric technologies that are based can inexpensively be integrated into cell phones that are effective for infants and young children;</li>
	<li>Novel low-cost methods to determine immune status at Point-of-Care that discriminate between vaccine-induced immunity and naturally-occurring immunity;</li>
	<li>Biomarker-based or other methods to determine vaccination history of infant/child populations;</li>
	<li>Solutions that can determine the vaccination status of a target population.</li>
</ul>

<h3>We will not consider funding for:</h3>

<ul>
	<li>Applications that require entire target population to have cell-phones to receive benefit;</li>
	<li>Applications that do not address the special considerations of biometrics in infants/children;</li>
	<li>Solutions to determining immune status that do not take into account local disease presence and resulting natural immune response and vaccine-derived immune response;</li>
	<li>Applications that do not have a clear idea of the cellular infrastructure in the targeted geographical area, or require cell phone ownership of the targeted population;</li>
	<li>Applications that do not consider the particular needs of target populations, such as literacy, and cultural impact.</li>
</ul>

<p>Grants will&nbsp;be selected on ability to create impact in the context of The Bill &amp; Melinda Gates Foundation’s existing global health priorities.For more information on these priority global health conditions, please&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">click here</a>.&nbsp;</p>


Create Low-Cost Cell Phone-Based Solutions for Improved Uptake and Coverage of Childhood Vaccination (Round 7)

<h2>What is the Challenge?</h2><p>2.1 billion of the&nbsp;world’s urban population use non-piped (non-sewered) sanitation technologies&nbsp;such as latrines, cesspools, septic tanks, or aqua privies to capture and contain their excreta (fecal matter and urine). These types of sanitation “solutions” tend to be unsustainable and are often detrimental to public health. Water used for irrigation, bathing, household activities, and drinking is contaminated with sewage and excreta. Pathogens in uncontained fecal matter are spread throughout communities particularly in urban areas. The consequences for the poor are profound: an estimated 1.6 million children die each year from diarrheal diseases, many of which are caused by fecal-oral contamination.</p><p>The purpose of this call for proposals is to help make sanitation services truly safe and sustainable for the poor. Improving human waste containment and management technologies can help achieve this goal while growing and strengthening the sanitation service sector and providing employment.</p><p>The challenge focuses on developing solutions in four specific areas associated with non-networked sanitation for the urban poor:</p><ol><li>Hygienic and adequate pit/tank emptying and extraction;</li><li>Recovery of energy from fecal sludge as a means for safe&nbsp;and affordable treatment and disposal;</li><li>Appropriate sanitation solutions for areas challenged by an abundance of water (e.g. communities that face seasonal flooding, high groundwater tables, riparian or tidal communities, etc.); </li><li>Easy to clean, attractive and affordable latrine pan / squatting platform technologies that enhance latrines.</li></ol><p><strong>1. Fecal sludge extraction</strong>: Pit latrines and septic tanks are emptied either by manual laborers (family members, marginalized community members, or local craftsmen) or by mechanical emptying devices (vacuum pumps and tankers) when they fill up. Unsafe manual pit emptying thrives in many cities because mechanical emptying is unavailable or prohibitively expensive ($30-80 for a typical latrine). If available, mechanical equipment is often too large to access the latrines/septic tanks along narrow roads and alleys or the pumping distance is too long to perform the operation. Even when equipment can reach users, emptiers tend to evacuate the liquid waste fraction but leave the dense, difficult-to-remove solids that accumulate at the bottom of the pit.</p><p><strong>2. Fecal sludge energy recovery</strong>:&nbsp;Fecal sludge tends to be a serious community liability despite the resource value available for energy recovery. The majority of evacuated fecal sludge is either dumped locally in nearby streets or drains or taken to dumping sites where little if any treatment takes place. The indiscriminate dumping of a truckload of fecal sludge is the public health equivalent of 5,000 incidences of open defecation. Fecal sludge, however, is a concentrate of organic material with high energetic value. Energy can be derived through digestion, extraction, or combustion, simultaneously reducing the volume of sludge that must be disposed.&nbsp; Unfortunately, relatively few facilities are designed to recover the energy value from sludge and many existing facilities have fallen into disrepair.</p><p><strong>3. Flooding and water challenges</strong>:&nbsp;The majority of the world’s population centers are located along coasts and rivers. The poorest communities in these cities, particularly in Asia, often live on marginal lands that are prone to water hazards or over water bodies directly. Those living in tidal, riparian, high water-table and otherwise flood-prone areas will face increasingly severe weather patterns as climate change progresses. Existing conventional or “alternative” sanitation options are inappropriate for these areas or are unaffordable for poor communities or poor governments. The result is severe contamination of the water resources that people rely on for their livelihoods and daily household activities. Chronic or seasonal flooding brings this contamination directly into neighborhoods and households.</p><p><strong>4. Latrine pan/squatting pan:</strong>&nbsp;Most latrines (dry or pour flush) do not match the esthetic standards and preferences of users to make them desirable and attractive enough to be built in their living environment or used frequently. Current alternatives to ceramic squatting pans or platforms are designed with materials that are not desirable or easy to clean.&nbsp;&nbsp;This can make latrines unusable after even a few usages, especially if the toilets are shared by several household members, schools pupils, or are in public toilet blocks. As a consequence, open defecation is often preferred to using existing latrines.&nbsp;Children, and particularly girls, do not use school facilities; public toilets fail to provide an adequate level of service for public hygiene.</p><h2>What&nbsp;we are looking for:</h2><p>We are seeking affordable, effective, and hygienic sanitation technology solutions that can improve the quality of sanitation services for the billions of people currently using non-piped sanitation systems.&nbsp; We are specifically seeking proposals for technologies that address emptying; energy recovery; wet-area sanitation challenges; and an attractive, desirable, and affordable pour flush pan/ squatting platform for latrines as briefly described above.</p><p>Proposed ideas must ultimately be designed for low income urban settings such as slums, informal and formal peri-urban settings, or dense rural settings in Sub-Saharan Africa and Asia where demand for fecal sludge emptying and treatment are high.</p><p>Innovations can be&nbsp;<u>new</u>&nbsp;ideas or&nbsp;<u>important improvements</u>&nbsp;to existing solutions. Proposals must provide an underlying rationale, a testable hypothesis, and an associated plan for how the idea would be tested or validated.</p><p><em>We will&nbsp;<u>NOT</u>&nbsp;fund behavior change programming (e.g., implementation of community led total sanitation or related approaches), boutique technologies that cannot be scaled, or technologies with capital or operating requirements that are inappropriate for serving the urban poor in developing countries.</em></p><h3>Areas for innovation to be considered include:</h3><p><strong>1. Hygienic manual or mechanical emptying equipment for urban areas.</strong>&nbsp;Technological solutions funded will enhance fecal sludge emptying business opportunities and improve quality and safety of service. Solutions/innovation should make emptying a hygienic activity with low operation and maintenance costs that allow emptying fees to be affordable to urban poor ($5-20 per latrine). Solutions should allow easy extraction of the consolidated heavy sludge accumulated in dry latrines or at the bottom of septic tanks. An advanced solution may allow safe filtration/separation of the solids fraction of fecal sludge&nbsp;<em>in situ</em>&nbsp;during an emptying operation. Ideally sludge transported to a designated disposal/processing site should have a high solids concentration.</p><p>Solutions should aim to meet as many of the following conditions as possible:&nbsp;&nbsp;</p><ul><li>Increases the number of pits than can be emptied per day;</li><li>Provides hygienic protection of the operator;</li><li>Allows for easy navigation and operation in narrow lanes;</li><li>Can be operated by maximum 2 persons;</li><li>Sludge can be safely emptied into receptacle suitable for at least 5-15 km of transport;</li><li>Removes heavy sludge/debris from the bottom of latrines/septic tanks;</li><li>Mechanical equipment should aim to access latrines as far as 50m away;</li><li>Separates solids/liquids in situ (i.e. dewatering);</li><li>Allows for potential on-site or “en route” treatment of evacuated liquids and/or solids for safe local disposal;</li><li>Based on affordable, robust, and locally available components.</li></ul><p><strong>2. Sludge processing for community energy generation in urban areas.</strong>&nbsp;Technology solutions funded will process sludge in a manner that generates energy that is ready to use for communities at a decentralized scale (bloc to district level) and that eliminates the contamination of remaining effluents and/or solids.</p><p>Solutions should aim to meet as many of the following conditions as possible:&nbsp;&nbsp;</p><ul><li>Low lifecycle costs, robust, and locally available components;</li><li>Easy to operate, maintain, and service during productive life;</li><li>Small land/space footprint at point of production and short processing/retention times (include quantitative estimates);</li><li>Capable of processing highly variable sludge inflow qualities and quantities;</li><li>Addresses odor nuisance;</li><li>High rate of sludge elimination, energy conversion efficiency, and effluent decontamination in the energy production process (proposals should include quantitative estimates);</li><li>Value of energy product generated should aim to cover operating costs of technology employed at a minimum (proposals should include quantitative estimates); </li><li>Energy end-product should be market and user friendly and not require expensive or new investments at the point of use;</li><li>Relevant for low-security settings;</li><li>Safety / backup mechanism in the case of system failure;</li><li>Proposals must explicitly and quantitatively articulate expected advantages of the proposed work relative to existing energy recovery technologies in the field.</li></ul><p><strong>3. Appropriate sanitation solutions for flooded zones (e.g. communities that face seasonal flooding, high groundwater tables, riparian or tidal communities, floating communities, etc.).</strong>&nbsp;Technologies should improve upon or develop new sanitation technologies that cope with wet-environment conditions.</p><p>Solutions should aim to meet as many of the following conditions as possible:&nbsp;</p><ul><li>Prevent infiltration from surface and/or groundwater;</li><li>Provide robust and safe containment during heavy rain and flood events;</li><li>Function in tidal, riparian, or floating communities;</li><li>Low lifecycle costs, robust, and locally available components;</li><li>Easy to operate, maintain, and service during productive life; </li><li>Incorporate user-centered design elements that are appropriate for women, children, and “washer” communities and that are affordable for the ultra-poor (&lt;$1/day);</li><li>Proposals should articulate clearly how the innovation improves upon existing technologies for these areas in terms of reduced cost, increased community/user appropriateness, increased robustness, or other critical factors;</li><li>Proposals should articulate clearly the type of water-challenged environment being targeted (e.g. tidal, seasonal flooding, etc.);</li><li>Individual excreta bagging solutions will not be considered for this call.</li></ul><p><strong>4. Easy cleaning, and affordable pan / squatting platform, suitable for connection to an offset pit.</strong> Attractive technologies that enhance latrine cleanliness and that have one or more of the following features:</p><ul><li>Easy to clean and smooth;</li><li>Attractive and offering a user experience and desirability similar to a ceramic pan;</li><li>Able to be mass produced;</li><li>Light weight and robust;</li><li>Durable; </li><li>Affordable.</li></ul><p>Grants will be selected on ability to create impact in the context of The Bill &amp; Melinda Gates Foundation’s existing global health priorities. For more information on these priority global health conditions, please <a href="https://www.gatesfoundation.org/our-work" target="_blank" title="">click here</a>.</p>

Create the Next Generation of Sanitation Technologies (Round 7)

<h2>Roadblock:</h2>

<p>Access to treatment with antiretroviral drugs is continuously expanding, reaching more patients in more countries that ever before. However, current therapies do not clear the infection, and patients require life‐long treatment to prevent the infection from progressing to more advanced forms of disease. The costs, scaling, and maintenance of this treatment for the growing HIV-affected population are daunting challenges. New methods need to be discovered that can permanently eliminate infection, even in cases where effects of the virus are being controlled with current antiretroviral drugs.&nbsp;<br />
<br />
The key challenge facing the development of a cure is perceived to be the presence of a reservoir of latently infected cells, principally CD4+ T-lymphocytes with a memory phenotype, representing as few as one in one million circulating immune cells. It is also possible that other long-lived, latently infected cell types, and cells to which there is limited accessibility to antiretroviral drugs and other agents, contribute to the latent reservoir. As a practical working definition, latently-infected cells are those that harbor HIV provirus that is largely transcriptionally silent, essentially impervious to the action of antiretroviral drugs, invisible to the immune system, yet is capable of reactivation to produce new HIV virions. Proposals&nbsp;<strong>must&nbsp;</strong>focus on characterizing or acting on latently-infected cells. Cure may be achieved in principle, by 1) preventing maintenance of the latent reservoir; 2) eradication or systematic depletion of the latent reservoir; or 3) rendering latently infected cells incapable of reactivation<strong>.</strong></p>

<h2>&nbsp;What We’re Looking For:</h2>

<p>The goal of this topic is to solicit new approaches to curing HIV infection in patients in whom a latent reservoir has already been established.&nbsp;&nbsp;Elimination of all reservoirs of HIV from a patient is a complex challenge that may require a combination of approaches. Consideration will be given to proposals that address any of the several different lines of study that could ultimately contribute to an effective cure. Proposals must (i) have a testable hypothesis, (ii) include an associated plan for how the idea would be tested or validated, and (iii) yield interpretable and unambiguous data in Phase I, in order to be considered for Phase II funding.</p>

<h3>A few of the many specific examples to be considered include:</h3>

<ul>
	<li>Approaches to selectively kill cells harboring HIV provirus without affecting uninfected bystander cells;</li>
	<li>Approaches to irreversibly inactivate HIV provirus in latently infected cells;</li>
	<li>New methods for identifying, characterizing, or isolating cells latently infected with HIV, to better inform strategies for their eradication;</li>
	<li>Identification of unique biomarkers/signatures on latently infected cells that would potentially enable identification, characterization, or selective targeting;</li>
	<li>New approaches to selectively re-activate expression of HIV RNA or proteins in latently infected cells, thereby permitting the targeting of these cells by a secondary agent, including but not restricted to antiretroviral drugs or immune mechanisms.</li>
</ul>

<h3>For this initiative, we will not consider funding for</h3>

<ul>
	<li>Studies that rely on intensification of antiretroviral therapy or structured treatment interruption;</li>
	<li>Approaches that involve non‐specific reactivation of HIV gene expression through use of cytokines, histone deacetylase inhibitors, DNA methylation inhibitors, etc., or otherwise rely on non-specific strategies for viral reactivation or elimination of latently-infected cells;</li>
	<li>Approaches that involve non-specific activation of HIV target cells, without regard for the presence or absence of HIV provirus;</li>
	<li>Methods to kill or inactivate productively infected cells, in which HIV RNA and proteins are abundantly expressed, rather than latently infected cells, where HIV RNA and proteins are generally not expressed;</li>
	<li>New approaches to reduce viremia or target cells in which HIV is actively replicating;</li>
	<li>Basic research studies of viral or cellular factors involved in the establishment or maintenance of latency without a clearly defined translational focus.</li>
</ul>

<p>Grants will&nbsp;be selected on ability to create impact in the context of The Bill &amp; Melinda Gates Foundation’s existing global health priorities.For more information on these priority global health conditions, please&nbsp;<a href="http://www.gatesfoundation.org/global-health/Pages/global-health-strategies.aspx" target="_blank" title="">click here</a>.&nbsp;</p>

<p><em>The NIH/NIAID is committed to providing opportunities for longer term funding of Grand Challenges projects in HIV latency and persistence that are productive during the course of the Challenge Award funding and are of high scientific merit.</em></p>
