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

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Makesense Daily: Your Personalized Engagement Journey to Solve the SDGs You Care About

Alizée Lozac'hmeurMakesenseParis, France
Grand Challenges
Global Citizenship
1 Nov 2018

Alizée Lozac'hmeur of Makesense in Paris will develop online mobile and web applications and provide opportunities to engage with experts and funders as part of a tailor-made approach to help young people learn about and solve the health and social issues that matter to them. They will integrate their digital platform, where participants can register their details and issue of interest, with a project database and events calendar to promote collaborations. Users will receive inspiration and advice and be informed of relevant opportunities by frequent emails or mobile phone messages to help them reach their goals. They will integrate the digital services, build a network of community organizers, and launch a marketing strategy to test their approach in France for engaging young people who are interested in solving a specific UN Sustainable Development Goal (SDG).

Young Adult Fiction and Technology to Create a Global Citizenship Process

Anna Gabriella CasalmeNovellySouth Gate, California, United States
Grand Challenges
Global Citizenship
1 Nov 2018

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.

Young Protectors: Mapping, Communicating, and Intervening to Reduce Disease Risk in Low-Income Communities

Hussein KhalilFederal University of Bahia (UFBA)Rio de Janeiro, Bahia, Brazil
Grand Challenges
Global Citizenship
1 Nov 2018

Hussein Khalil of the Federal University of Bahia in Brazil will provide young people in urban slums with knowledge and tools to identify elements that promote the spread of diseases by rats and mosquitos such as dengue and Zika virus infection, and engage their communities to help combat those diseases. They will recruit 40 young residents from two urban slums to test their approach. The youth will be taught to map rat- and mosquito-infested areas and identify possible causes, such as poor waste disposal, by photographing their environments, and to use tools to track rat movements and insect breeding. They will also use gamification methods to stimulate learning and promote collaborations between the youth and adult residents to identify the most effective interventions. Once simple solutions have been identified, the youth will help to implement them in their community and produce and share progress reports using online and offline tools.

Peace First Youth Challenge: Middle East

Eric DawsonPeace First Inc.Boston, Massachusetts, United States
Grand Challenges
Global Citizenship
1 Nov 2018

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.

The SDG Experience - Student Immersion in SDG Solutions Through Virtual Field Trips

Rimjhim AggarwalArizona State UniversityTempe, Arizona, United States
Grand Challenges
Global Citizenship
1 Nov 2018

Rimjhim Aggarwal of Arizona State University in the U.S. will use a digital learning platform and teaching network to teach young people how to create 360-degree spherical imagery of field sites that function as virtual field trips to share their experiences about specific UN Sustainable Development Goals (SDG) and better engage and teach others. These virtual field trips can be distributed on the internet, giving a large number of viewers the sense of actually being in the field, and are thus valuable teaching tools. However, they require specialized skills and equipment to create them. They will teach young people how to make them by holding a workshop to train 20 honors and undergraduate university students to create three new virtual field trips for local SDGs. These will then be presented to other students as part of a university course via a digital learning platform to evaluate their impact.

Enhancing Community Food Security in Urban and Rural Areas Through Outreach Youth Champions (EFSOYC)

Lucy Kathuri-OgolaKenyatta UniversityNairobi, Kenya
Grand Challenges
Global Citizenship
1 Nov 2018

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.

Creatively Empowering Youth and Kid Agripreneurs as Global Citizens to Achieve Food and Nutrition Security by 2050

Alpha SennonWHYFARMSiparia, , Trinidad and Tobago
Grand Challenges
Global Citizenship
1 Nov 2018

Alpha Sennon of WHYFARM in Trinidad and Tobago, along with Wainella Isaacs, Candace Charles-Sennon, Luke Smith, George Caesar, Akinola Sennon and their partners at TECH4Agri, will engage young people, who are the future feeders of 2050, in agriculture, and develop their knowledge and skills so that they can promote sustainable agriculture and improve food security in Trinidad and Tobago. They will implement four related projects in which participants can win cash prizes. These projects include an eight-week training course for ten professionals aged 18 to 30 that provides mentorship and skills to help develop their business plans, tours of ten primary schools with a local youth theater production company to teach nine to eleven year olds about the nutritional and economic value of baigan (eggplant), including a competition to design their own superheroes and nutritious snacks, and focusing their Agricultural Fun, Museum and Food Factory Park for the under 30's to teach visitors about food and local agricultural products using educational games. They will evaluate each project using surveys and metrics such as numbers of participants and related activity on social media.

Offline Teacher Training by Massive Open Online Courses

Romeo RodriguezWorld PossibleIrvine, California, United States
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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.

Edumocón Móvil: Taking 21st Century Teacher Training to Rural, Post-Conflict Colombia

Henry MaxCoschoolBogota, Cundinamarca, Colombia
Grand Challenges
Teaching and School Leadership
1 Nov 2018

Henry May of Coschool in Colombia will develop an integrated teaching course including in-person boot camps, mobile learning, and online communities, to equip teachers with advanced skills and tools to promote the wellbeing of themselves and their schools and communities. Teaching 21st century skills can help bridge the wide achievement gap between urban and rural communities in Colombia, and also help peace building in post-conflict territory. Their method focuses on five skills: growth mindset, self-awareness, empathy, critical thinking, and grit. To promote teaching of these skills, they have designed an integrated course that involves a six-hour boot camp for effective face-to-face teaching of large numbers of teachers; a twenty-hour course on a mobile, gamified platform; and monthly webinars for small groups with workshops and interactive learning. They will create the new course content and evaluate it by running the program over nine months with 1,000 teachers in five regions in Colombia.

Little Ripples

Sara-Christine DallainiACTRedondo Beach, California, United States
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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.

Project Heartbeat

Malcolm MooiDr CL Smith FoundationJohannesburg, , South Africa
Grand Challenges
Teaching and School Leadership
1 Nov 2018

Malcolm Mooi of the Dr CL Smith Foundation in South Africa will further develop their common online platform for teachers, which provides training, materials, and support to improve the quality of teaching in South Africa. Teachers are the number one drivers of learning in schools, but there is a lack of curriculum and holistic support for teachers in many countries, which has a direct, negative impact on student performance. They will use a variety of mathematical and technological approaches to refine their preliminary platform by adding new features to improve user experience and work to grow an online community of educators and organizers to attract more users. The performance of the platform will be measured by analyzing growth and user engagement. By exploring opportunities to connect the platform and associated data with education councils and corporations and unlock added value for teachers such as rewards and discounts, they aim to elevate the status of teachers in society and further improve teaching quality.

A Digital Platform for 21st Century Education

Saurabh AgarwalDeeper Learning Innovations Private LimitedLucknow, Uttar Pradesh, India
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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 21st 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.

Bringing STEM to Elementary School Teachers Using a Digital Platform

Yen VerhoevenParagon Learning Research GroupAmes, Iowa, United States
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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 21st 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.

Strengthening Youth Mental Health Outcomes and 21st Century Skills Through Progressive Music Instruction, Wellness and Collaborative Technologies

Anthony KolozettiMy School ROCKSMississauga, Ontario, Canada
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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 21st 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.

A Tutor for Every Child

Hans BrunnerValue Spring Technology, Inc.New York, New York, United States
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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.

The Birds and the Bees

Hira ZainabKnowledge Platform LimitedIslamabad, Pakistan
Grand Challenges
Teaching and School Leadership
1 Nov 2018

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.

A Population-Based Cohort Study in Matlab, Bangladesh: Establishing a Center of Excellence in Preterm Birth and Stillbirth Investigation

Anisur RahmanInternational Centre for Diarrhoeal Disease Research, BangladeshDhaka, Bangladesh
Grand Challenges in Global Health
Preventing Preterm Birth
1 Feb 2014

Anisur Rahman of the Matlab Health Research Centre at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICCDR,B) will lead a prospective cohort study of pregnant women, building on the ICDDR,B community-based surveillance site, to enroll more than 4,000 pregnant women over three years. His team will visit women monthly at their homes for early identification of pregnancy, followed by accurate gestational age dating by ultrasound and follow up throughout pregnancy and at delivery for collection of clinical data and specimens. The study includes standardized systems for documentation of complications of pregnancy and assessment of birth outcomes. Data and specimens will be used to advance innovative research into the causes of preterm birth and identify novel strategies for prevention.

Highly Sensitive Miniaturized Reader for Probe-based Isothermal Detection for Point-of-Care and Field Applications

Ann VinckierQIAGEN Sciences LLCGermantown, Maryland, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
14 Nov 2011

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.

Modified DNA Aptamer Affinity Reagents for Mtb Biomarker Validation

Dan FeldheimUniversity of ColoradoBoulder, Colorado, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
3 Nov 2011

Dan Feldheim of the University of Colorado at Boulder in the U.S. and collaborators Bruce Eaton of the University of Colorado and Delphi Chatterjee of Colorado State University propose to develop new modified DNA aptamer affinity reagents for detecting urine biomarkers of M. tuberculosis active disease. These reagents could form the basis of low­-cost, low­-power diagnostic sensors for use in resource-­limited settings.

Ultra-Sensitive Proteomic Quantitation of Circulating TB Biomarker Candidates by Complete Proteome SRM Assays

Robert MoritzInstitute for Systems BiologySeattle, Washington, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
20 Oct 2011

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.

Permeable Magnetic Nanoparticles for Point-Of-Care TB Diagnosis

David AllandUniversity of Medicine and Dentistry of New JerseyNew Brunswick, New Jersey, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
18 Oct 2011

David Alland of the University of Medicine and Dentistry of New Jersey in the U.S., in collaboration with Advantageous Systems (ADS), will develop a method that uses paramagnetic nanoparticles conjugated with capture antibodies to quickly extract M. tuberculosis bacteria from a patient's sputum sample. This simple extraction method can be applied to a broad range of detection technologies, enabling rapid tuberculosis detection.

Pathogen and Host Metabolites as Diagnostic Signatures of Tuberculosis

John BelisleColorado State UniversityFort Collins, Colorado, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
17 Oct 2011

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.

Disposable Sampling Plate and Breath Test to Identify Patients with Active Tuberculosis

James GrahamUniversity of LouisvilleLouisville, Kentucky, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
13 Oct 2011

James E. Graham, Xiao-­An Fu, Michael H. Nantz, and Richard M. Higashi of the University of Louisville in the U.S. will investigate the use of adsorptive sample plates with chemically reactive coatings to capture, identify, and validate unique volatile organic compounds found in breath samples of TB patients. This approach can establish the basis for a simple point of care test to identify active disease.

Exosomes as Biomarkers for Tuberculosis

Karen DobosColorado State UniversityFort Collins, Colorado, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
12 Oct 2011

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.

Validation of the Diagnostic Utility of Mtb Protein Biomarkers Found in Urine of TB Patients

Antonio Campos-NetoThe Forsyth InstituteCambridge, Massachusetts, United States
Grand Challenges in Global Health
Tuberculosis Biomarkers
12 Oct 2011

Antonio Campos­-Neto of The Forsyth Institute in the U.S. along with collaborators Nira Pollock of The Beth Israel Deaconess Medical Center/Harvard Medical School and David Duffy of Quanterix Corporation, seek to validate seven M. tuberculosis proteins found in the urine of tuberculosis patients as biomarkers of active disease. The ultimate goal is to use the most promising markers to develop a non-­invasive point-­of-­care test, which could be similar to a simple home­-pregnancy test.

Novel Reagents for the Serological Diagnosis of Tuberculosis

David AndersonMacfarlane Burnet InstituteMelbourne, Victoria, Australia
Grand Challenges in Global Health
Tuberculosis Biomarkers
11 Oct 2011

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.

A New Target for Mosquitocides

Jeffrey BloomquistUniversity of FloridaGainesville, Florida, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Aug 2011

Jeffrey R. Bloomquist of the University of Florida in the U.S. will investigate a voltage-sensitive potassium channel as a new target for mosquitocides.

Develop Synthetic Chemical Mimics of Selectively Insecticidal Natural Peptides

Robert KennedyVestaron CorporationKalamazoo, Michigan, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Aug 2011

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

Inducing Kidney Failure in Anopheles Gambiae

Peter PiermariniOhio State UniversityColumbus, Ohio, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Aug 2011

Peter M. Piermarini of the Ohio State University in the U.S. will use high throughput screening to discover chemicals that induce kidney failure in the malaria vector Anopheles gambiae.

Molecular Mosquitocides

Barry BeatyColorado State UniversityFort Collins, Colorado, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Aug 2011

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.

Quadruplex-based Technology for Isothermal DNA Amplification and Non-enzymatic Detection

Besik KankiaOhio State UniversityColumbus, Ohio, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
14 Jul 2011

Besik Kankia of the Ohio State University in the U.S. proposes to develop isothermal amplification of nucleic acids using a simple fluorescence detection method. If successful, the fluorescence signal will be detected by a portable fluorimeter or by eye after excitation with an appropriate light source.

Integrated Microfluidic Universal Sample Preparation and Pre-concentration (USP) Module for Parallel Diagnostics of Infectious Diseases (HIV, TB and Malaria)

Luke LeeUniversity of California, BerkeleyBerkeley, California, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
27 Jun 2011

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.

Microfluidic Immiscible Phase Barrier: Simplified Sample Preparation for Point-of-Care Diagnostics in the Developing World

David BeebeUniversity of WisconsinMadison, Wisconsin, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
27 Jun 2011

David Beebe and researchers at the University of Wisconsin in the U.S. propose to develop a “universal” sample purification platform that readily adapts to various upstream collection components and utilizes an immiscible phase (e.g. oil, wax) barrier to produce a “clean” sample for output to downstream amplification and detection components.

A Disposable Sub-system for Nucleic Acid Sample Preparation Without Instrumentation or User Intervention

Robert CaryMesa Tech International, Inc.Santa Fe, New Mexico, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
20 Jun 2011

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.

Enzyme-Free DNA Circuits for Signal Amplification and Diagnostic Assays

Andrew EllingtonThe University of Texas at AustinAustin, Texas, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
20 Jun 2011

Andrew Ellington of the University of Texas at Austin in the U.S. proposes to improve enzyme­-free DNA circuits by engineering circuit sensitivity and selectivity, ultimately creating multi­-layered circuits that greatly amplify signal inputs. These robust amplifiers could be modularly introduced into a variety of point­-of-­care diagnostics.

A Universal One-Step Device to Safely and Painlessly Collect Blood

Donald ChickeringSeventh Sense BiosystemsCambridge, Massachusetts, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
17 Jun 2011

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.

Low-Resource Extraction and Processing of Biological Samples Using Surface Tension Valves

Rick HaseltonVanderbilt UniversityNashville, Tennessee, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
16 Jun 2011

Rick Haselton, David Wright and Ray Mernaugh of Vanderbilt University in the U.S. propose to develop a sample processing technology that uses the surface tension between fluids as valves to separate, concentrate, and purify pathogen biomarkers. The proposed device aims to improve on existing biomarker extraction technologies in cost, simplicity, and speed.

Ambient Stable X-aptamer Affinity Agents

Ross DurlandAM Biotechnologies, LLCHouston, Texas, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
15 Jun 2011

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.

Self-amplifying DNA Polymers for Point-of-Care Diagnosis Through a Portable CMOS Sensor

Dan LuoCornell UniversityIthaca, New York, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
13 Jun 2011

Dan Luo of Cornell University in the U.S. proposes a “self­-amplifying-­DNA-­polymer” system in which monomers bind to specific pathogen biomarkers and then create polymer aggregates when exposed to light. This amplification step, to be used as a component for future diagnostic devices, is totally enzyme­-free and only occurs in the presence of specific pathogens.

Low-cost, High-sensitivity, Reconfigurable Optical Sensing Components for Point-of-Care Diagnostics

Rebecca Richards-KortumRice UniversityHouston, Texas, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
7 Jun 2011

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.

Protein Capture Agents With 40 °C Shelf Life for Developing World Point-of-Care HIV-1 Diagnostics

James HeathCalifornia Institute of TechnologyPasadena, California, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
6 Jun 2011

James Heath of the California Institute of Technology in the U.S. will work to develop protein catalyzed capture agents, which are synthetically-created peptides that may act as drop-in replacements for antibodies in diagnostic assays. These agents, designed to be stable up to 40°C for extended periods, aim to be as sensitive as antibodies, but due to their chemical structure, more easily transported, stored, and used in various diagnostic platforms in developing world settings.

Quantitative PCR Reconceived for Developing World Point-of-Care Diagnostics

Axel SchererCalifornia Institute of TechnologyPasadena, California, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
6 Jun 2011

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.

Modifying Mosquito Population Age Structure to Eliminate Dengue Transmission

Scott Leslie O'NeillUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges in Global Health
Biological Vector Control
1 Jul 2005

Scientists have long known that only relatively old mosquitoes can transmit the agents that cause certain diseases, including dengue fever and malaria. Dr. O'Neill and his multinational team are working on a plan to shorten the lifespan of mosquitoes that transmit the dengue virus, which infects up to 100 million people each year. They are introducing into populations of Aedes mosquitoes, strains of a naturally occurring bacterial symbiont, Wolbachia, that kill infected insects before they are old enough to transmit disease. Wolbachia are inherited though the eggs of the mosquitoes and so are passed on from generation to generation. O'Neill (Grand Challenges in Global Health: 2005-2015 retrospective)

Development of Bananas with Optimised Bioavailable Micronutrients

James DaleQueensland University of TechnologyBrisbane, Queensland, Australia
Grand Challenges in Global Health
Crop Biofortification
1 Jul 2005

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)

Linking Innate and Specific Immunity to Develop Single Dose Vaccines for Neonates

Lorne BabiukUniversity of SaskatchewanSaskatoon, Saskatchewan, Canada
Grand Challenges in Global Health
Single-Dose Vaccines
1 Jul 2005

Vaccinating infants against infectious disease is complicated by newborns' immature immune systems, the tendency of their immune systems to mount Th2-biased responses, and interference from maternal antibodies. Dr. Babiuk's team is working to develop new formulations of vaccines that can induce a long-lasting, balanced immune response in infants after a single­-administration vaccination.

Comprehensive Studies of Mechanisms of HIV Resistance in Highly Exposed Uninfected Women

Francis PlummerUniversity of ManitobaWinnipeg, Manitoba, Canada
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

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.

Novel Therapeutics That Boost Innate Immunity to Treat Infectious Diseases

Barton Brett FinlayUniversity of British ColumbiaVancouver, British Columbia, Canada
Grand Challenges in Global Health
Drug Resistance
1 Jul 2005

Dr. Finlay's team is investigating a new approach to treating bacterial and parasitic infections by enhancing the body's innate defense mechanisms. By acting on the cells of the immune system rather than on the disease-causing microbe directly, investigators expect to lessen the risk of developing drug-resistant organisms and the potential for broad-spectrum activity. The project team is focusing on a number of bacterial and parasitic pathogens, including enteric bacteria, Mycobacterium tuberculosis, and Plasmodium falciparum.

Development of Novel Mouse Models for HIV and HCV Infection

Hongkui DengPeking UniversityBeijing, China
Grand Challenges in Global Health
Vaccine Model Systems
1 Jul 2005

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.

Natural Products Inhibit Intracellular Microorganisms via Cellular Mechanisms

Jian-Dong JiangInstitute of Medicinal Biotechnology, Chinese Academy of Medical SciencesBeijing, China
Grand Challenges in Global Health
Drug Resistance
1 Jul 2005

Dr. Jiang’s team is identifying components of human cells that microbes use to establish an infection and replicate but that are not essential to the human host. Better understanding of microbial replication and survival from the view of host cells, the project team anticipates, will provide a foundation for novel therapeutic approaches to combat infectious diseases while simultaneously providing a low likelihood of inducing drug resistance. These compounds could potentially work by interrupting microbes from creating the environment they need to replicate in human cells.

Preclinical and Clinical Evaluation of Post-Exposure TB Vaccine

Peter AndersenStatens Serum InstitutCopenhagen, Denmark
Grand Challenges in Global Health
Curing Chronic Infection
1 Jul 2005

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.

Immunity to Prevent Pneumococcal Transmission: Correlates of Protection and Herd Immunity

Helena KäyhtyNational Institute for Health and WelfareHelsinki, Finland
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

Acute respiratory infections, often due to Streptococcus pneumoniae (pneumococcus), are a primary cause of death in young children in developing countries. A new vaccine effectively prevents the most serious form of pneumococcal disease and also reduces nasopharyngeal colonization with pneumococci. Because only some people who are infected become ill, researchers must study tens of thousands of vaccinated individuals over a long period of time to determine whether the vaccine guards against disease. Dr. Käyhty is leading an international consortium of investigators whose goal is to establish a quick and inexpensive method of determining the efficacy and expected effectiveness of the pneumonia vaccine.

Novel Mouse Models for Testing HIV and HCV Vaccines

Rudi BallingThe Helmholtz Centre for Infection ResearchBraunschweig, Germany
Grand Challenges in Global Health
Vaccine Model Systems
1 Jul 2005

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.

Biomarkers of Protective Immunity and Surrogate Markers of TB Disease in Africa

Stefan KaufmannMax Planck Society for the Advancement of Science EVBerlin, Germany
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

Tuberculosis (TB) is a major health problem, especially in developing countries. Dr. Kaufmann is leading an international consortium that is studying differences in immune system responses between people exposed to TB who never become sick and those who develop the disease, focusing particular attention on people infected with both HIV and TB in endemic African countries. The project's participating laboratories in Europe and the United States are attempting to learn which host responses provide protective immunity against TB and to identify correlates of protective immunity and host biomarkers of TB disease that could help guide the design and testing of improved TB vaccines, drugs, and diagnostics.

Engineering Rice for High Beta-Carotene, Vitamin E and Enhanced Fe and Zn Bioavailability

Peter BeyerAlbert Ludwigs Universitat FreiburgFreiburg, Germany
Grand Challenges in Global Health
Crop Biofortification
1 Jul 2005

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.

Surface Modified Nanostructures as Delivery Vehicles for Transmucosal Vaccination

Maria AlonsoUniversity of Santiago de CompostelaSantiago de Compostela, Spain
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

Most vaccines are delivered by injection, which increases the risk that HIV, hepatitis, and other serious diseases may be transmitted by syringes and needles that are not sterile. Dr. Alonso's team is working to develop a new generation of delivery systems that can easily and effectively carry hepatitis B vaccine through the mucosal lining of the nose. In addition, the team is evaluating whether these delivery systems and the vaccine they carry can be freeze-dried into an inhaled powder that could be stored without refrigeration.

Enhancing the Immunogenicity and Efficacy of Vectored Vaccines

Adrian HillUniversity of OxfordOxford, United Kingdom
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

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)

Novel Antigen Design and Delivery for Mucosal Protection Against HIV-1 Infection

Robin ShattockSt. George's Hospital Medical SchoolLondon, United Kingdom
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

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.

Learning from the Human Genome How Protective Immunity Against Malaria Works

Dominic KwiatkowskiUniversity of OxfordOxford, United Kingdom
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

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)

Homing Endonuclease Genes: New Tools for Mosquito Population Engineering and Control

Austin BurtImperial College LondonLondon, United Kingdom
Grand Challenges in Global Health
Biological Vector Control
1 Jul 2005

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)

Drugs for Treatment of Latent Tuberculosis Infection

Douglas YoungImperial College LondonLondon, United Kingdom
Grand Challenges in Global Health
Curing Latent Infection
1 Jul 2005

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)

A Live Recombinant Attenuated Salmonella Anti-Pneumococcal Vaccine for Newborns

Roy CurtissArizona State UniversityTempe, Arizona, United States
Grand Challenges in Global Health
Single-Dose Vaccines
1 Jul 2005

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.

Bacterial Spores as Vaccine Delivery Systems

Abraham SonensheinTufts University School of MedicineMedford, Massachusetts, United States
Grand Challenges in Global Health
Vaccines Without Refrigeration
1 Jul 2005

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.

Increasing Vaccine Stability Through Novel Technology

Juan AlvarezTransForm Pharmaceuticals, Inc.Lexington, Massachusetts, United States
Grand Challenges in Global Health
Vaccines Without Refrigeration
1 Jul 2005

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.

Thermostable Vaccines With Improved Stability at Non-Refrigerated Temperatures

Claire CoeshottEndo Pharmaceuticals, IncBoulder, Colorado, United States
Grand Challenges in Global Health
Vaccines Without Refrigeration
1 Jul 2005

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.

Development of a Targeted Mucosal Vaccine Delivery Technology

David LoUniversity of California, RiversideRiverside, California, United States
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

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.

Nanoemulsions as Adjuvants for Nasal-Spray Vaccines

James BakerUniversity of MichiganAnn Arbor, Michigan, United States
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

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)

Needle-Free Delivery of Stable, Respirable Powder Vaccine

Robert SieversAKTIV-DRY LLCBoulder, Colorado, United States
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

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)

Needle-free Vaccination via Nanoparticle Aerosols

David EdwardsPresident and Fellows of Harvard CollegeCambridge, Massachusetts, United States
Grand Challenges in Global Health
Needle-Free Vaccines
1 Jul 2005

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.

A Mouse Model to Evaluate Live Attenuated Vaccine Candidates

Richard FlavellYale UniversityNew Haven, Connecticut, United States
Grand Challenges in Global Health
Vaccine Model Systems
1 Jul 2005

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)

A Protective Genetically Attenuated P. Falciparum Sporozoite Vaccine

Stefan KappeSeattle Biomedical Research InstituteSeattle, Washington, United States
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

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)

Improved Vaccine Efficacy via Dendridic Cells and Flavivirus Vectors

Ralph SteinmanRockefeller UniversityNew York, New York, United States
Grand Challenges in Global Health
Antigen Design
1 Jul 2005

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.

Molecular Analysis and Modeling of HIV-1 Transmission, Containment and Escape

George ShawUniversity of AlabamaBirmingham, Alabama, United States
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

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)

Protective Immunity Against Severe Malaria in Young Children

Patrick DuffySeattle Biomedical Research InstituteSeattle, Washington, United States
Grand Challenges in Global Health
Protective Immunity
1 Jul 2005

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.

Developing Novel Transgenic Strategies for Introducing Dengue Virus Refractivity in Mosquito Cells and Tissues

Malcolm FraserUniversity of Notre DameNotre Dame, Indiana, United States
Grand Challenges in Global Health
Biological Vector Control
1 Jul 2005

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.

Genetic Strategies for Control of Dengue Virus Transmission

Anthony JamesUniversity of California, IrvineIrvine, California, United States
Grand Challenges in Global Health
Biological Vector Control
1 Jul 2005

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.

Disruption of Malaria Transmission by Chemical Manipulation of Anopheline Olfactory Responses

Laurence ZwiebelVanderbilt UniversityNashville, Tennessee, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Jul 2005

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)

Molecular Approaches to Alter Olfactory-Driven Behaviors of Insect Vectors

Richard AxelColumbia UniversityNew York, New York, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Jul 2005

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)

Molecular Design of Selective Anticholinsterases for Mosquito Control

Jeffrey BloomquistVirginia Polytechnic Institute and State UniversityBlacksburg, Virginia, United States
Grand Challenges in Global Health
Chemical Vector Control
1 Jul 2005

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.

Improving Cassava for Nutrition, Health and Sustainable Development

Richard SayreOhio State University Research Foundation & Donald Danforth Plant Science CenterSt. Louis, Missouri, United States
Grand Challenges in Global Health
Crop Biofortification
1 Jul 2005

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.

Nutritionally Enhanced Sorghum for the Arid and Semi-Arid Tropical Areas of Africa

Paul AndersonAfrica Harvest Biotech Foundation InternationalNairobi, Kenya
Grand Challenges in Global Health
Crop Biofortification
1 Jul 2005

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.

Engineering Immunity Against HIV and Other Dangerous Pathogens

David BaltimoreCalifornia Institute of TechnologyPasadena, California, United States
Grand Challenges in Global Health
Curing Chronic Infection
1 Jul 2005

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)

Immunological Strategies for Curing Chronic Hepatitis Virus Infections

Rafi AhmedEmory UniversityAtlanta, Georgia, United States
Grand Challenges in Global Health
Curing Chronic Infection
1 Jul 2005

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.

Novel Therapeutic Vaccines for Acute and Persistent Papollomavirus Infections

Robert GarceaUniversity of ColoradoBoulder, Colorado, United States
Grand Challenges in Global Health
Curing Chronic Infection
1 Jul 2005

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.

Population Health Metrics Research Consortium Project

Christopher MurrayPresident and Fellows of Harvard College & University of WashingtonSeattle, Washington, United States
Grand Challenges in Global Health
Population Health Status
1 Jul 2005

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.

A Point-of-Care Diagnostic System for the Developing World

Paul YagerUniversity of WashingtonSeattle, Washington, United States
Grand Challenges in Global Health
Point-of-Care Diagnostics
1 Jul 2005

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.

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