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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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"Bulletin Board" For Broadcasting Vaccine Supply/Demand

Arun RamanujapuramLogistimoBangalore, , India
Grand Challenges Explorations
Immunization Systems
5 Apr 2012

Arun Ramanujapuram of Logistimo, Inc. in India proposes to develop a mobile-phone based "bulletin-board" for capturing and broadcasting availability and demand information for vaccines and medicines. By bringing real-time visibility to these essential goods, stock can be appropriately redistributed to areas of need, and waste can be reduced.

"Coffee Ring Stain" Diagnostics for Malaria

David WrightVanderbilt UniversityNashville, Tennessee, United States
Grand Challenges Explorations
Diagnostics
1 Nov 2009

David Wright of Vanderbilt University in the U.S. will develop a new low-cost diagnostic tool in which a droplet of malaria-infected blood deposited on a glass slide will, based on fluid dynamics, leave a ring-like pattern as the blood evaporates. The slide will be prepared with a solution that will interact with a particular protein of the malaria parasite to visualize this "coffee ring stain," allowing for easy interpretation and ready diagnosis.

0.70%

Jack McPartlandFuture Buro Pty LtdSydney, New South Wales, Australia
Grand Challenges Explorations
Communicating About Aid
3 Oct 2012

Jack McPartland of Future Buro in Australia will work to turn the figure "0.7%" – which is the United Nations target for aid donations from the Gross Domestic Product (GDP) of developed countries – into a brand that can be communicated to tell the story about the proportionally small amount of financial resources needed to make an impact in the developing world. After branding is created, Future Buro will work to secure partnerships to facilitate donations of 0.7% of incomes, budgets, and media space to expand the reach of targeted communications about the positive impact of foreign aid.

4°C Simple Passive Vaccine Storage Device

Keith BartlettTrue EnergyTywyn Gwynedd, Wales, United Kingdom
Grand Challenges Explorations
Immunization Systems
8 Oct 2012

Keith Bartlett of True Energy in the United Kingdom will work with stakeholders in the immunization community to create a prototype vaccine storage device that uses the properties of water density to maintain vaccines at 4°C during the "last mile" of the cold chain. A water container that maintains the liquid at a steady temperature of 4°C will be in contact with the vaccine storage area, preventing temperature fluctuations that can damage or destroy vaccines.

A Bacterial Protease Inhibitor is a Mucosal Adjuvant

Juliana CassataroInstituto de Estudios de la Inmunidad Humoral, CONICETBuenos Aires, Argentina
Grand Challenges Explorations
Mucosal Immunity
1 May 2010

Juliana Cassataro of the Universidad Nacional de San Martín-CONICET in Argentina will test whether the bacterial protease inhibitor Omp19 can make vaccines more effective when they are administered orally. Oral delivery of vaccines is far simpler than by injection, which is particularly useful in low-resource settings, and it may also stimulate mucosal immunity making them more effective against some diseases. However, most vaccines administered orally are degraded in the stomach or do not induce a sufficient immune response to protect against the disease. In Phase I, while at the Universidad de Buenos Aires-CONICET, they discovered that Omp19 protects antigens from degradation and serves as an adjuvant, contributing to induction of both a mucosal and systemic immune response in mice orally immunized with proteins from the Salmonella bacterium and the Toxoplasma parasite, both of which have mucosal routes of infection. In Phase II, they will extend their mechanistic studies in order to move towards a Phase I clinical trial, and evaluate the ability of Omp19 to help induce an immune response in mice upon oral vaccination against Enterotoxigenic E. coli (ETEC), which is the most common cause of bacterial diarrhea in children from developing countries.

A Biotic Stress Sensor Printed on Maize Leaves

Hideaki TsutsuiUniversity of California, RiversideRiverside, California, United States
Grand Challenges Explorations
Protecting Crop Plants
1 May 2012

Hideaki Tsutsui of the University of California, Riverside in the U.S. will develop a low-cost stamp to directly print biosensors on maize leaves for colorimetric detection of biotic stresses. The strategy is to develop an immunochromatographic assay using microneedle probes while printing an easily-read color-change detector.

A Buddy Program for Immunisation System Managers

Ben GilbertUniversity of CanberraCanberra, Australian Capital Territory, Australia
Grand Challenges Explorations
Immunization Systems
24 Oct 2012

Ben Gilbert and Andrew Brown of the University of Canberra in Australia will develop a regional support network for medical supply managers in Pacific Island countries that can help them to better apply the formal training they received to manage vaccine supply systems. By engaging them in a buddy support system, Gilbert and Brown hope to empower these managers to overcome cultural, educational, social and historical factors that hinder effective management styles, and help them operate supply systems that are more responsive to immunization challenges in those developing countries.

A Device for Self-Sampling of Blood for Infectious Disease

Ian MatthewsCardiff UniversityCardiff, United Kingdom
Grand Challenges Explorations
Global Health Solutions
11 Apr 2012

Ian Matthews of Cardiff University in the United Kingdom proposes to develop a self-sampling micro-needle patch device for the collection of small volumes of blood. Micro-needles will be fabricated using Deep Reactive Ion Etching. The device will permit non-refrigerated transport of collected blood for subsequent assays for diagnosis of infectious disease.

A Diagostic Test for Poor Anti-TB Drug Bioavailability

Christopher VinnardDrexel UniversityPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Global Health Solutions
2 Apr 2012

Christopher Vinnard of Drexel University in the U.S. proposes to develop a low-cost point-of-care urine test that can safely and accurately identify tuberculosis patients who poorly absorb anti-TB drugs. Testing patients for inadequate drug bioavailability could enable better drug dose optimization and decrease transmission rates.

A Disposable SIM Card Biosensor for Rapid Malaria Detection

Peter LillehojUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
Cell Phone Applications
1 Nov 2010

Peter Lillehoj and Chih-Ming Ho of the University of California, Los Angeles in the US. will develop a disposable malaria biosensor based on a SIM card platform. This SIM card-biosensor will allow malaria detection to be performed using a cell phone, making diagnostic testing more widely available in rural and decentralized settings.

A High Throughput Mosquito Assay

Koen DecheringTropIQ Health SciencesNijmegen, Netherlands
Grand Challenges Explorations
Malaria Drugs
12 Oct 2012

Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries. In Phase I, they tested several barcoding strategies and identified a bacterium that could be genetically modified to carry a unique barcode for identifying hit compounds selected in the screen. They also developed the luminescent reporter parasite to track transmission. In Phase II, they will further develop the assay for higher throughput, and screen compounds from the Tres Cantos Antimalarial Set and the MMV Validation, Malaria and Pathogen boxes. They will also use the assay to characterize the mechanisms of action of other candidate transmission-blocking compounds.

A Lab-on-Mobile-Device Platform for Seed Testing

Donald CooperMobile Assay IncBoulder, Colorado, United States
Grand Challenges Explorations
Protecting Crop Plants
15 Oct 2012

Donald Cooper of Mobile Assay Inc. in the U.S. will develop a low-cost, highly sensitive smartphone-based platform that employs phone cameras to image and amplify signals from immunoassay rapid test strips to detect Botrytis and aflatoxin infection in seeds or soil. Connecting phone data to a cloud server would allow farmers to monitor seed and crop quality and enable the development of regional preventative strategies.

A Lexicon of HIV-RNA Interactions

Alice TelesnitskyUniversity of MichiganAnn Arbor, Michigan, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

Alice Telesnitsky of the University of Michigan in the U.S. seeks to define and characterize HIV interactions with host RNA. The team will attempt to determine whether disrupting or mimicking essential interactions with host RNAs may lead to antiviral strategies to which HIV cannot readily develop resistance.

A Low-Cost Cooling Device in Neonatal Encephalopathy

Sudhin ThayyilUniversity College LondonLondon, United Kingdom
Grand Challenges Explorations
Global Health Solutions
9 Oct 2012

Sudhin Thayyil of the University College London in the United Kingdom, along with Seetha Shankaran of Wayne State University in the U.S. and Balraj Guhan of Calicut Medical College in India, will develop and validate a low-cost, low-technology whole body cooling device that operates on a proven servo-controlled algorithm with minimal supervision. This device could reduce death and disability resulting from neonatal encephalopathy in developing countries where expensive cooling equipment and trained healthcare providers are scarce.

A Low-Cost Phonogram Device for Screening Fetal Wellbeing

Ahsan KhandokerKhalifa UniversityAbu Dhabi, United Arab Emirates
Grand Challenges Explorations
Global Health Solutions
11 Oct 2012

Ahsan Khandoker of Khalifa University in the United Arab Emirates will build a low-cost, non-invasive abdominal phonogram device that can be used on a mobile phone to assess sounds that indicate fetal well being such as heart rate and body movement. The device will employ a software algorithm to extract fetal noises in an acoustic signal from maternal and environmental noises, allowing health care workers in remote locations to conduct obstetric assessments without expensive or invasive equipment.

A Low-Cost, Rapid, and Sensitive Malaria Diagnostic Tool

Sang-Yeon ChoNew Mexico State UniversityLas Cruces, New Mexico, United States
Grand Challenges Explorations
Diagnostics
1 May 2010

Sang-Yeon Cho and Immo Hansen of New Mexico State University in the U.S. seeks to develop a malaria test that measures antibody-antigen reactions through a nanohole to indicate the presence of malaria parasites.

A Microbial Platform for the Biosynthesis of New Drugs

Christina SmolkeStanford UniversityStanford, California, United States
Grand Challenges Explorations
Synthetic Biology
30 Mar 2012

Christina Smolke of Stanford University in the U.S. will develop synthetic biology platforms to improve the scale and efficiency of microbial systems used to discover, develop, and produce drugs based on natural products. Such new biosynthesis approaches could lead to new and less expensive drugs for global health.

A Microencapsulation Technique to Target Desert Locust

Ravi DurvasulaBiomedical Research Institute of New MexicoAlbuquerque, New Mexico, United States
Grand Challenges Explorations
Protecting Crop Plants
1 Oct 2012

Ravi Durvasula of the Biomedical Research Institute of New Mexico in the U.S. is developing biopolymers to encapsulate and protect fungal biopesticides, which are used to kill desert locusts that destroy crops in Africa. The polymer will not only shield the biopesticides from harsh environmental conditions such as UV radiation and heat but will also be formulated to release its contents upon contact with the insect.

A Mobile Cloud System to Achieve Universal Vaccination

Alain LabriqueJohns Hopkins UniversityBaltimore, Maryland, United States
Grand Challenges Explorations
Immunization Systems
18 Apr 2012

Alain Labrique of Johns Hopkins Bloomberg School of Public Health in the U.S. will develop and field test in rural Bangladesh a cloud-based mobile phone system that will allow for universal access to vaccination records, send vaccine reminders and messaging, and provide incentives to parents and health care workers via a phone application. This new strategy could increase the reach, coverage, and public acceptance of immunization.

A Mobile Phone Enabled Diagnostic Platform for Monitoring Drug Compliance

Amit SrivastavaChildren's Hospital BostonBoston, Massachusetts, United States
Grand Challenges Explorations
Cell Phone Applications
1 Nov 2010

Amit Srivastava of Children's Hospital, Boston in the U.S., along with colleagues at MIT, will develop a novel drug compliance platform combining the use of mobile phones for a simple diagnostic test, with economic incentives. The device will include a platform that measures drug metabolites in bodily fluids to generate a readout. Test results submitted on time will result in immediate economic rewards, such as additional cell phone minutes.

A New Platform for Vaccine Delivery Capable Of Eliciting a Mucosal Immune Response

Daniel SteinUniversity of MarylandCollege Park, Maryland, United States
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

Daniel Stein and Phillip DeShong of the University of Maryland in the U.S. will construct and test a vaccine platform that utilizes low-cost, stable surfactant vesicles to deliver antigens for a sustained mucosal immune response. If successful, the platform could be used to develop low-cost vaccines for bacterial infections where carbohydrates form the basis of protective immunity, such as bacterial pneumonia and diarrheal diseases.

A New Strategy for Resistant and More Nutritious Rice

Aymeric GoyerOregon State UniversityCorvallis, Oregon, United States
Grand Challenges Explorations
Protecting Crop Plants
17 Oct 2012

Aymeric Goyer of Oregon State University and Pamela Ronald of the University of California, Davis in the U.S. will develop rice plants that accumulate higher levels of thiamine (vitamin B1) to test the theory that boosting thiamine enhances the plant's resistance to disease. This strategy could lead to crops that can not only resist two devastating pathogens, Xanthomonas oryzae and Magnaporthe grisea, and lead to higher yields, but also produce rice of higher nutritional value.

A New Tool for Anti-Malarial Target Gene Validation

Philip ShawNational Center for Genetic Engineering and BiotechnologyPathumthani, Thailand
Grand Challenges Explorations
Malaria Eradication
5 Oct 2009

Philip J. Shaw of Thailand's National Center for Genetic Engineering and Biotechnology will seek to identify potential drug targets and vaccine antigens in the malaria parasite using a novel technology to reduce specific gene expression. By fusing a natural genetic “riboswitch” onto gene targets, the team will attempt to attenuate gene expression and thereby determine gene function.

A New Way to Prevent HIV Infection During Breastfeeding

David SokalFamily Health InternationalDurham, North Carolina, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

David Sokal of Family Health International in the U.S., with colleagues at Cambridge and Drexel Universities, will develop and test low-cost filters coated with safe microbicides that can be inserted into tips of nipple shields to prevent HIV transmission during breastfeeding.

A New Whole-Organism Vaccine Against Malaria

Miguel PrudencioInstituto de Medicina MolecularLisbon, Portugal
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

Miguel Prudencio of Instituto de Medicina Molecular in Portugal will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness. This was successfully tested in Phase I, and they also established that the human antigens carried by the parasites could induce a selective immune response in mice. In Phase II, they will test their vaccine in Phase I/IIa human trials and evaluate it for safety, tolerability, and immunogenicity. They will also extend their approach to another human malaria parasite P. vivax, and begin optimizing methods for large-scale vaccine production.

A Newborn Cry-Based Diagnosis System

Chakib TadjÉcole de Technologie SupérieureMontreal, Quebec, Canada
Grand Challenges Explorations
Mothers and Newborns
1 Nov 2010

Chakib Tadj of École de Technologie Supérieure in Canada will design a non-invasive diagnostic tool using computer acoustical analysis of newborn cries to detect serious medical conditions such as heart defects and infections. Cry production in newborns can be influenced by neurological and physiological states. In this project's Phase I, Tadj and his team analyzed cries from 120 healthy and sick newborns to identify acoustic features that can be used for diagnostic purposes. In Phase II, they will build on these results by incorporating an additional 1000 infants, and expanding to other serious pathological conditions afflicting newborns. They will also develop a software-based diagnostic tool that can interpret recorded cries to help neonatologists detect specific pathologies affecting newborns.

A Non-Pathogenic Chimeric THLV-1/HIV-1 Viral Genome as a Model to Study Superinfection Restriction

Kuan-Teh JeangNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Kuan-Teh Jeang of the National Institutes of Health in the U.S. will investigate whether cells infected by one virus become resistant to infection from other viruses, and if this viral interference can confer protection against HIV. The team will develop an attenuated virus to test whether over-expression of viral envelope proteins within cells can confer resistance to further HIV infection.

A Novel Approach of Creating an Attenuated Pneumonia Vaccine

Vijay PancholiOhio State University Research FoundationColumbus, Ohio, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Vijay Pancholi of The Ohio State University Research Foundation in the U.S. will attempt to attenuate the S. pneumonia bacteria by altering export of the GAPDH enzyme, a function thought to be essential to the bacteria's survival. Preventing export of this key enzyme will decrease bacterial virulence, allowing the attenuated strain to be used for development an affordable live vaccine for pneumococcal pneumonia.

A Novel Bactericidal Protein Found in Milk

Anders HakanssonThe Research Foundation of the State University of New YorkAlbany, New York, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

Anders Hakansson of the University of Buffalo in the U.S. has identified a protein from human breast milk (Human Alpha Lactalbumin Made Lethal to Tumor cell, or HAMLET), that kills respiratory tract bacteria. Hakansson will attempt to understand the mechanism by which HAMLET binds to and kills pheumococci without the bacteria developing resistance.

A Novel Effective Vaccine Against Cholera

Michael LebensUniversity of Gothenburg Institute for Vaccine ResearchGothenburg, Sweden
Grand Challenges Explorations
Vaccines
5 Oct 2009

Michael Lebens of the University of Gothenburg Institute for Vaccine Research in Sweden proposes to develop a new oral cholera vaccine using a single cholera strain that expresses antigens for both the Inaba and Ogawa serotypes and produces cholera toxin subunits that act as an adjuvant to stimulate mucosal immune activity. In this project’s Phase I research, Lebens and his team successfully generated potential vaccine candidate strains that express both Ogawa and Inaba type antigens simultaneously. They also demonstrated in an animal model that oral immunization with these bacteria in a killed formulation elicited immune responses similar to those obtained by vaccination with currently licensed oral killed whole-cell cholera vaccines. In Phase II, he will further improve these strains by inducing them to express an accompanying adjuvant and conduct immunogenicity analyses and other work to prepare for a Phase I trial.

A Novel Female-Controlled Antiviral Contraceptive

Renjie ChangLavaxPalantine, Illinois, United States
Grand Challenges Explorations
Contraceptive Technologies
1 Nov 2010

Renjie Chang of Lavax in the U.S. will develop and test a vaginal suppository that uses a strain of commensal bacteria which has the ability to immobilize sperm and capture viruses. If successful, the bacteria could be used as a reversible contraceptive that also affords protection against viruses such as HIV and herpes.

A Novel Method for Controlling Fertility and STD

Robert AitkenUniversity of NewcastleCallaghan, New South Wales, Australia
Grand Challenges Explorations
Contraceptive Technologies
1 May 2010

John Aitken of the University of Newcastle in Australia will study the mechanisms by which organic compounds called quinones may provide simultaneous protection against pregnancy and sexually transmitted disease. Aitken will test the capability of quinones to react to enzymes in semen and not only immobilize sperm, but also disrupt the infective nature of pathogenic microbes found in STD infections such as Chlamydia

A Novel Test to Measure Mucosal Immunity to Vaccines

Giulietta SalettiInternational Vaccine InstituteSeoul, South Korea
Grand Challenges Explorations
Mucosal Immunity
1 May 2010

Giulietta Saletti of the International Vaccine Institute in the Republic of Korea will work to develop an assay test that binds to tissue-specific cell markers to not only measure the concentration of anti-body secreting cells, but also identify which of those cells are targeted to mucosal tissues. If successful, this simple test that requires a small blood sample can be used in low-resource settings to measure mucosal immune responses to vaccines in infants and children.

A Novel Vaccination Strategy for Cutaneous Leishmaniasis

Jesus ValenzuelaNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Because Leishmania is transmitted to humans when sand flies feed on humans, Jesus Valenzuela of the National Institutes of Health in the U.S. proposes to develop a novel vaccine against salivary proteins of sand flies with the aim to induce a strong immune response against the parasite.

A Novel Virulence-Associated Malaria Drug Target

Paul GilsonBurnet InstituteMelbourne, Victoria, Australia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Paul Gilson of Macfarlane Burnet Institute for Medical Research and Public Health in Australia will study the function of a newly discovered malaria parasite mechanism that exports proteins into host red blood cells in an effort to develop compounds that block this transfer and inhibit parasite growth.

A Novel Way of Controlling Malaria Transmitting Mosquitoes

Jasper Ogwal-OkengMakerere UniversityKampala, Uganda
Grand Challenges Explorations
Infectious Diseases
1 May 2010

Jasper Ogwal-Okeng of Makerere University in Uganda will test whether the insect-eating plants can reduce the population of mosquitoes and their larvae. Ogwal- Okeng will study optimal numbers and placement of such plants and record subsequent impact on mosquito and larvae populations to further refine this vector control method.

A Novel Way of Targeting TB using Aptamers and Nanotechnology

Boitumelo SemeteCouncil for Scientific and Industrial ResearchPretoria, South Africa
Grand Challenges Explorations
Drug Resistance
1 May 2009

To optimize the effectiveness of current anti-tuberculosis drugs, Boitumelo Semete of the CSIR in South Africa will work with collaborators to develop “sticky nanoparticles” that specifically attach to TB-infected cells. Once taken in by these cells, the nanoparticles will slowly degrade, releasing the anti-TB drugs and killing the bacteria. With this novel drug delivery system, the team aims to improve the bioavailability of the current therapies, with the possibility of shortening the treatment period for TB as well as reduce drug side effects.

A Passive Solar Thermal Standard for Vaccine Storage Rooms

Loriana DembeleEau et Vie - Ji DumaBamako, Mali
Grand Challenges Explorations
Immunization Systems
18 Oct 2012

Loriana Dembele of Eau et Vie Ji-Duma in Mali proposes to develop new architectural and construction guidelines for vaccine storage rooms in hot climates that incorporate passive solar thermal technologies to keep vaccines at recommended temperatures. The team will construct and test prototype storage facilities to determine new standards that prevent vaccine spoilage, reduce operating costs, and improve refrigeration capabilities.

A Predictive Model for Vaccine Testing Based on Aptamers

Alexander DouglasJenner InstituteOxford, United Kingdom
Grand Challenges Explorations
Synthetic Biology
2 Apr 2012

Alexander Douglas of the Jenner Institute, University of Oxford in the United Kingdom will use synthetic nucleic acid molecules known as aptamers to develop a model that can be used to predict the success or failure of new vaccines in clinical trials. This work could help to remove some of the uncertainty in the early-stage development of new vaccines.

A Probiotic-based Approach To Improve Child Nutrition

Alip BorthakurUniversity of Illinois at ChicagoChicago, Illinois, United States
Grand Challenges Explorations
Nutrition
10 Apr 2012

Alip Borthakur of the University of Illinois at Chicago in the U.S. will characterize the effects of probiotics on epithelial uptake of the fatty acid butyrate in vitro and in a mouse model to inform therapeutic strategies to cure and prevent acute diarrhea and malnutrition in children.

A Quantum Physics Search for Liver-Stage Antimalarials

David SullivanJohns Hopkins UniversityBaltimore, Maryland, United States
Grand Challenges Explorations
Malaria Drugs
18 Oct 2012

David Sullivan of the Johns Hopkins Bloomberg School of Public Health in the U.S., along with Martin N. Martinov of Gradient Biomodeling LLC, will create a quantum physics computer model of liver-stage malaria parasite infection to screen existing commercial drug and compound databases to identify molecules that possess liver-stage specific anti-malarial activity. Those molecules will then be tested in vivo and in vitro, and the ones that are effective will be optimized via computer modeling for future pre-clinical development.

A Rapid and Portable Assay for Detecting Neonatal Sepsis

Douglas WeibelUniversity of WisconsinMadison, Wisconsin, United States
Grand Challenges Explorations
Global Health Solutions
9 Oct 2012

Douglas Weibel of the University of Wisconsin-Madison in the U.S. proposes to develop a portable diagnostic system that uses inexpensive plastic assay cartridges that wick samples into chambers loaded with reagents to detect bacteria associated with neonatal sepsis. The cartridges will be attached to a smart phone loaded with an application that collects data and transmits results to a clinical lab for further treatment instructions.

A Self-Adjuvanting Vaccine for ST-ETEC

Roy Robins-BrowneUniversity of MelbourneMelbourne, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

Enterotoxigenic E. coli (ETEC) is the leading cause of diarrhea in the developing world. Roy Robins-Browne, of the University of Melbourne, in Australia will evaluate the effectiveness of a prototype vaccine that combines enterotoxin of E. coli (which lacks immunogenicity by itself) with another epitope to attract helper T cells and a lipid adjuvant to ensure delivery of the antigen directly into the cell.

A Simple and Specific Screening Method for M.tb Infection

Guozhi WangNational Institute for the Control of Pharmaceutical & Biological ProductsBeijing, China
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

Guozhi Wang of the National Institute for Control Pharmaceutical & Biological Products in China will assess the effectiveness of a new inexpensive skin test that can differentiate between true Tuberculosis infection and the markers of the BCG vaccination. Because the current TB screening protocol is not sensitive enough to tell the difference, this new test could lead to earlier and better treatment options for those with early-stage infections.

A Single Strategy to Attack Insect Vector and Transmitted Virus

Stéphane BlancInstitut National de la Recherche AgronomiqueParis (cedex 07), France
Grand Challenges Explorations
Protecting Crop Plants
1 May 2012

Stéphane Blanc of the Institut National de la Recherche Agronomique (INRA) in France will minimize the destructive effects of aphids on crop plants by studying a newly described structure, the acrostyle, which is found at the tip of the piercing mouthparts of the insects and thought to be important for feeding and for transmitting disease-causing viruses between plants. Aphids spread an array of different plant viruses to many crop species including banana, chickpea, and sweet potato. Work during Phase I involved developing tools including acrostyle-targeting antibodies and methods to genetically manipulate aphids, which led to the identification of one protein in the acrostyle that is likely to be a receptor for the cauliflower mosaic virus. Consistent with this, binding of this virus to the insect could be blocked with an antibody targeting that specific protein. In Phase II, they will complete their cataloguing of peptides at the acrostyle using mass spectrometry to identify more candidate receptors that are important for virus binding and transmission, and potentially also for insect feeding. These peptides will be further analyzed using newly developed genetic tools to determine their precise function. They will also use structural methods including nuclear magnetic resonance to identify key amino acid residues in the peptides that could be exploited to block both virus transmission and insect feeding, and thereby weaken the aphids.

A Single Vaccine Against Pneumococcus and Typhoid Fever

Yingjie LuChildren's Hospital BostonBoston, Massachusetts, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Yingjie Lu and Richard Malley of Children's Hospital Boston in the U.S. will develop a bivalent pneumococcal and typhoid vaccine by using a new technology to include three highly conserved pneumococcal antigens and the well-established Vi polysaccharide antigen that provides protection against typhoid fever. The team will test the ability of this vaccine to induce strong humoral and cellular immune responses against both pneumococcus and the causative agent of typhoid fever, Salmonella Typhi. In this project’s Phase I research, the team successfully developed the bivalent vaccine and in initial research was able to demonstrate dual immunity to both pneumococcus and S. Typhi. In Phase II, they will perform further proof-of-concept experiments in animal models that will provide support for the clinical development of this bivalent vaccine candidate.

A Single-Step Device for Monitoring Mucosal Iga Titers

Kevin PlaxcoUniversity of California Santa BarbaraSanta Barbara, California, United States
Grand Challenges Explorations
Diagnostics
7 Apr 2010

Kevin Plaxco of the University of California, Santa Barbara, United States seeks to develop a diagnostics platform based upon measuring the electric current produced by the binding of antibodies to DNA molecules. If successful, this method will provide a rapid, single-step reagent free measurement of immune antibodies which could significantly augment disease detection and vaccine validation efforts.

A Small Molecule That Blocks Male-to-Female Sexual Transmission of HIV

David EisenbergUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Recent evidence suggests that HIV infection may be drastically enhanced when a specific protein found in human semen is present in fibril form. David Eisenberg of UCLA in the U.S. will design and test a small peptide that can effectively block formation of fibrils on this protein. If successful, the therapy could be administered via spray or liquid drops to inhibit transmission of HIV.

A Strategy for Control of Plant Virus Diseases

Amitava MitraUniversity of Nebraska-LincolnLincoln, Nebraska, United States
Grand Challenges Explorations
Protecting Crop Plants
9 Oct 2012

Amitava Mitra of the University of Nebraska in the U.S. will investigate direct repeat- induced gene silencing, a phenomenon of RNA interference in which genes adjacent to a target gene are also silenced. This "transitive silencing" will be tested for its ability to target multiple crop viruses at once, allowing the development of a transgenic wheat strain that is resistant to multiple major diseases.

A Synthetic Biosensor to Find Drugs Targeting TB Persistence

Robert AbramovitchMichigan State UniversityEast Lansing, Michigan, United States
Grand Challenges Explorations
Synthetic Biology
2 Apr 2012

Robert Abramovitch of Michigan State University in the U.S. will use their high-throughput drug discovery platform to identify new drugs for treating chronic tuberculosis and for potentially shortening the current treatment time of six to nine months. Their platform exploits a genetic region known as the DosR regulon thought to underlie the behavior of the causative bacteria in humans under low oxygen conditions, when they become dormant and thereby resistant to current drugs. In Phase I, they screened over 250,000 compounds and identified around 170 candidates that could either stop bacterial persistence under low oxygen conditions or could potently inhibit bacterial growth. In Phase II they will optimize one of the candidate DosR regulon inhibitors and test the ability of this class to block chronic infection, as well as characterizing the compounds that inhibit bacterial growth.

A Therapeutic Strategy to Control HIV-1 Infection

Qigui YuIndiana UniversityBloomington, Indiana, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Antibodies and the complement system work together to specifically detect and clear viruses, but they are circumvented by HIV, which hides itself and the cells it infects by hijacking host proteins such as CD59. Qigui Yu of Indiana University School of Medicine in U.S. will attempt to unmask HIV and HIV-infected cells and render them susceptible to antibody-complement attack. In this project's Phase I research, Yu and his team identified a potent, specific, and non-toxic inhibitor of human CD59, which is used by HIV to escape destruction by antibody-complement attack. In Phase II, Yu will continue to research how this inhibitor might allow antibodies to regain their complement-mediated activity to destroy the virus and HIV-infected cells, and will also research how HIV-1 incorporates human CD59 onto viral particles to escape antibody-complement immunity.

A Tissue-Engineered Mosquito Midgut Assay

Thomas NeumannNortis BioSeattle, Washington, United States
Grand Challenges Explorations
Global Health Solutions
9 Oct 2012

Thomas Neumann of Nortis, Inc. in the U.S. will develop a tissue-engineered model of the mosquito midgut for use in an in vitro assay on a disposable, chip-like microfluidic device. This device could be developed into a standardized and automated platform to screen anti-malarial compounds that target the parasite in the mosquito before transmission to human hosts.

A Totally New Approach to Discover Malaria Combination Drugs

Melvin ReichmanLIMR Chemical Genomics Center IncWynnewood, Pennsylvania, United States
Grand Challenges Explorations
Malaria Drugs
8 Oct 2012

Melvin Reichman of the LIMR Chemical Genomics Center Inc. in the U.S., working with Vicky Avery of the Eskitis Institute for Cell and Molecular Therapies in Australia, will develop and validate a new drug screening approach called Ultra-High Throughput Screening for Synergy (uHTSS) to discover new drug combinations from the Tres Cantos anti-malarial set for the treatment of malaria.

A Toxin-Binding Probiotic for Prevention Of ETEC Diarrhea

Adrienne PatonUniversity of AdelaideAdelaide, South Australia, Australia
Grand Challenges Explorations
Infectious Diseases
1 May 2010

Enterotoxigenic Escherichia coli (ETEC) cause diarrhea by producing two distinct enterotoxins that attack intestinal cells. Adrienne Paton and colleagues at the University of Adelaide in Australia propose to develop a harmless probiotic bacterium capable of binding and neutralizing both these enterotoxins by mimicking their respective receptors, thereby preventing disease.

A Transformational Vaccine Platform for Rotavirus

Anton MiddelbergUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Global Health Solutions
11 Apr 2012

Anton Middelberg of the University of Queensland in Australia proposes to develop a new vaccine for rotavirus by the directed self-assembly of a safe virus-like particle in industrial reactors. The approach uses low-technology engineering methods suitable for the developing world, ensuring relevance to the communities most in need of vaccine.

A Transmission-Blocking Vaccine Against Dengue Virus Dissemination

Gong ChengTsinghua UniversityBeijing, China
Grand Challenges Explorations
China Tsinghua-GCE
1 Jan 2012

Gong Cheng of Tsinghua University in China will develop a transmission-blocking vaccine against dengue virus that takes advantage of blocking mosquito infection by targeting the transmission from human to mosquito.

A Trick To Control Malaria: Manipulating the Mosquito Innate Immune Response

Sumi BiswasJenner InstituteOxford, United Kingdom
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

Sumi Biswas of the Jenner Institute, University of Oxford in the United Kingdom will test three components from the mosquito's innate signaling pathways for possible use in a malaria vaccine. Biswas will test whether immunizing mammal hosts with these components can induce strong antibodies, which can be passed along to mosquitoes to enhance the insect's innate immune response, thus leading to the death of the malaria parasite in the vector.

A Vaccine Against Salmonella

Wendy PickingOklahoma State UniversityStillwater, Oklahoma, United States
Grand Challenges Explorations
Global Health Solutions
16 Oct 2012

Wendy Picking and a team at Oklahoma State University in the U.S. will work to develop a new vaccine for Salmonella that uses a serotype-independent Salmonella antigen combined with an adjuvant to deliver immunity against all serotypes of the bacteria. This vaccine, when administered intradermally, could be a cost-effective way to reduce the overall incidence and severity of diarrhea in children in the developing world.

A VLP-Based Phage Display System for HIV Vaccine Discovery

Bryce ChackerianUniversity of New MexicoAlbuquerque, New Mexico, United States
Grand Challenges Explorations
Vaccines
1 May 2009

Bryce Chackerian and David Peabody at the University of New Mexico in the U.S. have developed a new phage display system based on highly immunogenic virus- like particles (VLPs), and will utilize this new system as a platform to identify new vaccines that induce broadly neutralizing antibodies against HIV.

A Zeolite Hydrogel 'Nano-Mop' For Contraception

Benson WamalwaUniversity of NairobiNairobi, Kenya
Grand Challenges Explorations
Contraceptive Technologies
1 May 2010

Benson Wamalwa of the University of Nairobi in Kenya will develop and test a vaginal gel that contains zeolite nanoparticles which soak up the fructose present in semen. By “mopping” up the fructose, this gel will rob sperm of the energy needed for motility. If successful, the gel could be used as an inexpensive, non-hormonal contraceptive.

Accelerating Vaccine Development Against P.vivax Malaria

James BeesonBurnet InstituteMelbourne, Victoria, Australia
Grand Challenges Explorations
Global Health Solutions
30 Mar 2012

James Beeson and Damien Drew of the Burnet Institute in Australia propose to generate chimeric Plasmodium falciparum that expresses the antigens of another malaria parasite, P. vivax, allowing them to be evaluated as vaccine candidates. Because laboratory culturing of P. vivax is costly and technically difficult, this new method could help accelerate the development of vaccines against malaria caused by P. vivax.

Adjuvant Effects of a Special Light

Mei WuGeneral Hospital CorporationBoston, Massachusetts, United States
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Laser light at a specific setting can activate antigen presenting cells in the skin and temporarily make cellular membranes permeable. Mei X. Wu and colleagues at Massachusetts General Hospital/Harvard Medical School in the U.S. will test whether injection of a vaccine into laser-exposed skin can significantly enhance immune responses stimulated by the vaccine.

Aerosol Delivery of Synthetic Lung Surfactant

Frans WaltherLos Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterTorrance, California, United States
Grand Challenges Explorations
Global Health Solutions
2 Apr 2012

Frans Walther of the Los Angeles Biomedical Research Institute in the U.S. will adapt a low-cost synthetic lung surfactant for aerosol delivery as a non-invasive and simple method to support breathing in premature infants. Surfactant is composed of lipids and proteins, and keeps the lungs open during expiration. It is normally administered to premature infants with breathing difficulties by tracheal intubation, which can be problematic in low-resource settings and cause side effects. In Phase I, they produced the surfactant aerosol and found that it improved oxygenation and lung function in a small animal model. In Phase II, they will continue preclinical development by analyzing different application methods, dosing levels, and safety, and evaluate dry surfactant formulations that would not require refrigeration.

Aid is Working. Just Ask G.I. Joe.

Robin McQueenCenter for National PolicyWashington, District of Columbia, United States
Grand Challenges Explorations
Communicating About Aid
1 Oct 2012

Robin McQueen of the Truman National Security Institute in the U.S. will work to reframe the concept of foreign aid as effective and essential to national security. A short film trailer will be produced featuring trusted voices of military veterans to explain how aid mitigates crises that can cause global instability. The trailer will be presented with innovative methods of visual and mobile communications to prompt viewers to link to a website for more information. Viewer demographics will be tracked to target groups for further education campaigns.

An "Evolution-Proof" Bio-Pesticide to Control Malaria

Jason RasgonJohns Hopkins UniversityBaltimore, Maryland, United States
Grand Challenges Explorations
Infectious Diseases
1 May 2010

Jason Rasgon of the Johns Hopkins Bloomberg School of Public Health in the U.S. will engineer a virus to express a scorpion toxin that kills mosquitoes. After infecting mosquito larvae, the virus will express the killer gene when the insect becomes old enough to reproduce, but not old enough to transmit the malaria parasite. By allowing the mosquito to reproduce, the virus not only will be transmitted vertically to the next generation, but will also significantly slow the evolution of resistance to the gene.

An "Oral Contraceptive" For Male Anopheles Mosquitoes

Luna KamauKenya Medical Research InstituteNairobi, Kenya
Grand Challenges Explorations
Global Health Solutions
5 Apr 2012

Luna Kamau of the Kenya Medical Research Institute in Kenya will investigate how feeding on selected compounds affects male Anopheles mosquito fertility and subsequently, mating competiveness. The compounds could be presented in sugar meals or introduced into larval breeding sites to control mosquito population densities, thereby reducing malaria transmission.

An Altruistic Vaccine for Mosquito Transmitted Pathogens

Paul YoungUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Mosquito transmitted pathogens such as dengue and malaria are a significant disease burden on the world's population. Paul Young of the University of Queensland in Australia aims to develop a novel vaccine approach that is based on blocking mosquito transmission of these disease agents rather than inducing pathogen- specific immunity.

An Arabinomannan-Protein Conjugate Vaccine for Tuberculosis

Arturo CasadevallAlbert Einstein College of Medicine of Yeshiva UniversityBronx, New York, United States
Grand Challenges Explorations
Global Health Solutions
16 Oct 2012

Arturo Casadevall of Albert Einstein College of Medicine in the U.S. will work to develop a new vaccine for tuberculosis that uses an arabinomannan-protein conjugate to elicit strong antibody-mediated immunity. M. tuberculosis has a polysaccharide capsule composed of arabinomannan, which, when used as part of a vaccine, could lead to an immune response that prevents inflammation and disease transmission without impairing clearance of the bacteria.

An Endothelial Reservoir for Malaria?

Michael LeibowitzRobert Wood Johnson Medical SchoolPiscataway, New Jersey, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Michael Leibowitz of the UMDNJ-Robert Wood Johnson Medical School in the U.S. will investigate whether malaria parasites bind to, invade and replicate in the endothelial cells that line the blood vessels to test the theory that endothelial cells play an important role in the development of malaria infection and may serve as undiscovered reservoirs for parasite latency.

An Immunity-Enhancing Beverage

Steven MaranzCornell UniversityIthaca, New York, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Steven Maranz of Weill Medical College in the U.S. will test the hypothesis that providing children high levels of flavanols, compounds found in chocolate, green tea, cola and shea nuts, deprives malaria parasites of lipids needed to survive, keeping parasite infection at levels low enough to elicit a strong immune response that builds lifelong immunity.

An Innovative "Inject & Forget" Contraceptive Drug Delivery Device

Gerrard PoinernMurdoch UniversityPerth, Western Australia, Australia
Grand Challenges Explorations
Contraceptive Technologies
1 Nov 2010

Gérrard Poinern of Murdoch University in Australia will develop and test an implantable subcutaneous device made from same calcium mineral that bones are made of, which will release contraceptive drugs in a sustained and controlled way for a period of months. Creating of this device uses ultrasound and microwave technology, allowing for eventual low-cost manufacture in developing countries.

An Optical "Seek-And-Destroy" System To Vaccinate Against Leishmania Infection

Owain MillingtonUniversity of StrathclydeGlasgow, United Kingdom
Grand Challenges Explorations
Infectious Diseases
1 May 2010

Owain Millington and Gail McConnell of University of Strathclyde in the United Kingdom seek to adapt existing imaging systems to provide non-invasive in vivo imaging of Leishmania parasites present in macrophages and dendritic cells, and then use a targeted laser to destroy them. They will also test the hypothesis that targeting these cells for destruction will stimulate protective immunity against future Leishmania parasite infections.

Anti-Malarial Compounds That Target the Cytostomal Endocytic Pathway

Michael KlembaVirginia Polytechnic Institute and State UniversityBlacksburg, Virginia, United States
Grand Challenges Explorations
Malaria Drugs
22 Oct 2012

Michael Klemba of Virginia Polytechnic Institute and State University in the U.S. will identify anti-malarial compounds from the Malaria Box that function as inhibitors of the cytostomal endocytic pathway used by the malaria parasite P. falciparum to internalize host erythrocyte proteins. Characterizing the molecular mechanisms of this process could lead to the discovery of new anti-malarial compounds.

Anti-Microbial/HIV-1 Peptide as a Vaginal Contraceptive

Nongnuj TanphaichitrOttawa Hospital Research InstituteOttawa, Ontario, Canada
Grand Challenges Explorations
Contraceptive Technologies
1 Nov 2010

Nongnuj Tanphaichitr of the Ottawa Hospital Research Institute (formerly Ottawa Health Research Institute) in Canada will research whether the antimicrobial peptide LL-37 can be used simultaneously as a contraceptive and an anti-HIV treatment. LL-37 binds to specific sites on sperm which are thought not only to play key roles in egg fertilization but also interact with gp120 used by HIV to gain entry into cells.

Anti-TB Drugs That Limit Evolution of Resistance

Gerald SmithFred Hutchinson Cancer Research CenterSeattle, Washington, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

Gerald R. Smith of the Fred Hutchinson Cancer Research Center in the U.S. seeks to identify inhibitors of a bacterial DNA repair enzyme that allows tuberculosis to mutate. Identifying these inhibitors could lead to therapies that kill bacteria and limit drug resistance.

Arginine Metabolism in Indian, Jamaican and American Women

Farook JahoorBaylor College of MedicineHouston, Texas, United States
Grand Challenges Explorations
Nutrition
30 Mar 2012

Farook Jahoor of Baylor College of Medicine in the U.S. will conduct studies to test whether healthy women in India produce less arginine, an amino acid critical for a successful pregnancy, than pregnant Jamaican and American women and will research the underlying mechanisms to inform possible interventions to reduce the number of low birth weight babies in India.

Artificial Triggering of Malaria Parasite Relapse

Lena HuldenUniversity of HelsinkiHelsinki, Finland
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Lena Hulden of the University of Helsinki in Finland will test the hypothesis that saliva from newly emerging mosquitoes activates dormant P. vivax parasites in the liver. By robust statistical analysis of the timing of P. vivax outbreaks, as well as molecular analysis of mosquito saliva, Hulden hopes to eventually identify the trigger for these relapses in hopes of controlling outbreaks.

Aspergillus-Resistant Aflatoxin-Free Transgenic Groundnuts

Monica SchmidtUniversity of ArizonaTucson, Arizona, United States
Grand Challenges Explorations
Protecting Crop Plants
16 Oct 2012

Monica Schmidt of the University of Arizona and Dilip Shah of the Danforth Center in the U.S. will work to develop a fungal resistant, aflatoxin-free transgenic groundnut by simultaneously suppressing fungal growth and inhibiting the fungus' ability to biosynthesize the mycotoxin compound. This may eliminate carcinogenic mycotoxin contamination making groundnuts safe for consumption.

Assessing Environmental Impacts of Immunization Technologies

Ruth StringerHealth Care Without HarmReston, Virginia, United States
Grand Challenges Explorations
Immunization Systems
9 Oct 2012

Ruth Stringer and a team at Health Care Without Harm in the U.S., and colleagues at the Health Care Foundation Nepal, will design and test a decision-making tool that compares the costs, benefits, and environmental impacts of centralized autoclaving, recycling, and/or disposing of various types of conventional and safety syringes. This tool will enable decision makers to choose the most economical and sustainable medical waste management strategy.

Assessment of Fusarium Endophytes For Use in Sub-Saharan Africa

Jeffrey ColemanRhode Island HospitalProvidence, Rhode Island, United States
Grand Challenges Explorations
Protecting Crop Plants
8 Oct 2012

Jeffrey Coleman of Rhode Island Hospital and the Warren Alpert Medical School of Brown University in the U.S. seeks to identify isolates of the fungus Fusarium that are capable of establishing a beneficial relationship with important crop plants in Sub-Saharan Africa. These endophytes could be used to increase crop production while preventing the invasion of disease-causing pathogens.

Azithromycin Administration to Prevent Growth Faltering in Gambian Infants: Understanding Mechanisms for Public Health Intervention

David MabeyLondon School of Hygiene and Tropical MedicineLondon, United Kingdom
Grand Challenges in Global Health
Achieving Healthy Growth
1 Jan 2012

David Mabey of the London School of Hygiene and Tropical Medicine in the United Kingdom and his team will test whether treatment with the broad­-spectrum antibiotic azithromycin can prevent growth faltering linked to environmental enteropathy, which is prevalent in young children of developing countries. They will utilize a double blind, randomized, controlled trial of Malawian children aged 1­-60 months, and analyze growth over a two year period after a single administration of either the antibiotic or a placebo control. They will also analyze immune responses and composition of the intestinal microbiota to identify the molecular pathways underlying environmental enteropathy. Their aim is to improve growth and development in affected infants in low­-income countries.

Bacillus-fermented Natto as Edible Vaccines

Michael ChanOhio State UniversityColumbus, Ohio, United States
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

Michael Chan of the Ohio State Research Foundation in the U.S. will develop an engineered strain of bacteria used to ferment beans in traditional Asian and African diets, to display an antigen from the Tuberculosis bacterium. The engineered bacillus will then be used to make the traditional Asian dish natto, which can serve as a kind of oral vaccine to elicit a strong immune response. If successful, this strategy can be used to introduce a variety of disease antigens through culturally accepted foods.

Bacillus-Fermented Natto as Edible Vaccines for the Developing World

Michael ChanThe Chinese University of Hong KongHong Kong, China
Grand Challenges Explorations
Protecting Crop Plants
4 Oct 2012

Michael Chan of the Ohio State Research Foundation in the U.S. will develop an engineered strain of bacteria used to ferment beans in traditional Asian and African diets, to display an antigen from the Tuberculosis bacterium. The engineered bacillus will then be used to make the traditional Asian dish natto, which can serve as a kind of oral vaccine to elicit a strong immune response. If successful, this strategy can be used to introduce a variety of disease antigens through culturally accepted foods.

Bacterial Viruses as Tool for Blocking Transmission of Malaria

Luiz OzakiVirginia Commonwealth UniversityRichmond, Virginia, United States
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Luiz Ozaki and Gail E. Christie of Virginia Commonwealth University in the U.S. will genetically engineer bacterial viruses to carry peptides that block the development of the malaria parasites, survive in the mosquito gut, and spread through vector populations. If successful, these bacteriophages could be used as “gene dissemination tools” for effective control of the malaria.

Bacteriophage Lambda Mucosal Vaccine Delivery System

Sylvia van den HurkUniversity of SaskatchewanSaskatoon, Saskatchewan, Canada
Grand Challenges Explorations
Mucosal Immunity
1 May 2010

Sylvia van den Hurk and Sidney Hayes of the University of Saskatchewan in Canada proposes that bacteriophage lambda, a virus that invades bacterial cells and uses the host's genome to replicate, can be used as a vector to deliver DNA vaccines into targeted cells. Van den Hurk will test this lambda delivery platform its ability to induce long-term systemic and mucosal immune responses.

Balance of Th17 Cells and Regulatory T Cells in Candidal Vaginal Colonization in Pregnant Macaques and Humans

Margaret HostetterCincinnati Children's Hospital Medical CenterCincinnati, Ohio, United States
Grand Challenges in Global Health
Preventing Preterm Birth
1 Jan 2012

Margaret Hostetter from Cincinnati Children's Hospital Medical Center in the U.S. and her co-investigators will examine how disruption of the normal bacteria and other micro-organisms (the microbiome) of the lower female genital tract may increase risk of preterm birth. These investigations will focus on vaginal Candida infections in pregnancy, inflammation, and regulation of the immune response. Research will be conducted using animal models and laboratory investigations connected to studies of women in low-resource countries. Their goal is to investigate protective and pathogenic mechanisms of preterm birth and identify novel treatment strategies for vaginal fungal infections to prevent preterm birth. Funding partners: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) and Bill & Melinda Gates Foundation.

Bi-directional Membrane Device for Child Delivery

Sergey ShevkoplyasTulane UniversityNew Orleans, Louisiana, United States
Grand Challenges Explorations
Global Health Solutions
3 Apr 2012

Sergey Shevkoplyas, Lakhinder Kamboj, and Noshir Pesika of Tulane University in the U.S. will develop a microfabricated bidirectional membrane that can be placed in the mother's vagina just prior to delivery to facilitate the baby's passage through the birth canal. This simple-to-use device could significantly improve outcomes during vaginal deliveries in resource limited settings.

BioClay - Managing Biotic Stresses From Field to Market

Neena MitterUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Protecting Crop Plants
1 May 2012

Neena Mitter of The University of Queensland in Australia will develop a 'BioClay' technology to deliver biological agents that kill crop pathogens and pests. This technology could provide broad spectrum protection to crops without the need for transgenic plants or the use of chemicals.

Biologic Contraceptive

Rachel TeitelbaumHervana, Ltd.Beit Shemesh, Israel
Grand Challenges Explorations
Contraceptive Technologies
1 May 2010

Rachel Teitelbaum of Hervana, Ltd. in Israel will develop and test a biological vaginal formulation that produces a sperm-binding agent, which interferes with sperm motility or fertilization or both. It is hoped that this non-hormonal contraceptive will need only infrequent administration to maintain its effectiveness. In this project's Phase I research, Teitelbaum developed a lead formulation and demonstrated initial proof-of-principle that such an approach can provide effective contraception. In Phase II, Teitelbaum and her team will expand upon this proof-of-principle in animal models to arrive at a long-acting, safe, and effective contraceptive that is ready for evaluation in human trials.

Biological Control For Sandflies Using Free-Living Fungi

Peter NgureDaystar UniversityNairobi, Kenya
Grand Challenges Explorations
Infectious Diseases
23 Apr 2010

Peter Ngure of Daystar University in Kenya seeks to develop a biological control for sandflies using fungi found in the local soil in Kenya. These entomopathogenic fungi, which attach like parasites onto adult insects and larvae and kill them, will be harvested and cultured to isolate virulent strains that can eradicate sandflies, which are responsible for the spread of visceral leishmaniasis.

Biological Control of Mosquitoes with Bti-Engineered Algae

David HerrinThe University of Texas at AustinAustin, Texas, United States
Grand Challenges Explorations
Infectious Diseases
1 Nov 2010

David Herrin and colleagues at the University of Texas propose to develop a green-algal food source for mosquito larvae into a biological control agent by engineering their chloroplasts to produce larvacidal proteins. The chloroplast genome has significant advantages for genetic modification, including stability and containment.

Biomarkers and Interventions to Prevent Preterm Birth and Stillbirth Associated with Placental Malaria

Kevin KainUniversity Health NetworkToronto, Ontario, Canada
Grand Challenges in Global Health
Preventing Preterm Birth
1 Jan 2012

Kevin Kain of the University Health Network and the University of Toronto in Canada will investigate malaria infections of the placenta to reveal specific roles of the immune response that lead to preterm birth, low birth weight, and stillbirth. This project will focus on discovering biomarkers to identify at-risk pregnancies as well as new interventions to prevent adverse pregnancy outcomes. Funding partners: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) and Bill & Melinda Gates Foundation.

Biomarkers of Gut Function and Predictors of Linear Growth and Neurodevelopment Status Among Young Tanzanian Children

Christopher DugganChildren's Hospital BostonBoston, Massachusetts, United States
Grand Challenges in Global Health
Gut Function Biomarkers
23 Oct 2012

Christopher Duggan of Children’s Hospital Boston in the U.S. and his team will test whether known biomarkers of gut dysfunction can accurately predict impaired neurodevelopment and stunting, which reflects chronic malnutrition and is associated with increased morbidity and mortality in young children. The biomarkers will be validated in a well­-characterized group of young Tanzanian children. The goal is to facilitate the identification of at risk children early in life, so that appropriate intervention strategies can be applied.

Biomarkers of in utero Aflatoxin Exposure and Child Growth

Zdenko HercegWHO-IARC (International Agency for Research on Cancer)Lyon Cedex, France
Grand Challenges Explorations
Nutrition
20 Apr 2012

Zdenko Herceg of the International Agency for Research on Cancer (IARC) in France will evaluate the impact of seasonal dietary aflatoxin exposure of pregnant women in rural Africa by identifying epigenetic biomarkers of exposure, growth impairment, and disease risk. This will facilitate the development of interventions to improve child health.

Biomarkers of Nutrition Related Cognitive Development

Clare ElwellUniversity College LondonLondon, United Kingdom
Grand Challenges Explorations
Nutrition
3 Apr 2012

Clare Elwell of University College London in the United Kingdom is using non-invasive optical brain imaging (near-infrared spectroscopy) to assess cognitive function in malnourished infants and children in low-resource settings over time. The technology is relatively low-cost and portable, and their approach could be used to determine the impact of malnutrition on the developing brain and guide nutrition-related interventions. In Phase I, they performed functional brain imaging in the presence of specific stimuli on 99 infants aged 0-2 years old in a rural setting in The Gambia over a 10-month period. This established proof-of-principle of their approach for measuring brain function in the field. In Phase II, they will expand the study to include 250 infants who will also be evaluated for additional physical, behavioral and cognitive parameters and analyzed every four months. This dataset will then be used to identify markers of disrupted cognitive development for early intervention, to provide insight into the role of malnutrition and other factors such as disease, and to help monitor treatments.

Biosynthetic Immunotargeting for Pneumococcal Treatment

David SpiegelYale UniversityNew Haven, Connecticut, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

David A. Spiegel of Yale University in the U.S. will pursue an antibiotic strategy called “biosynthetic immunotargeting.” Streptococcus pneumoniae will be fed small molecules which they will incorporate into their cell walls. These small molecules contain an epitope recognized by antibodies in the human bloodstream, leading to immune clearance independent of bacterial antigens, representing a unique, resistance-free approach to pneumococcal disease.

Blocking the P. falciparum Transporter PfCRT

Christine HrycynaPurdue UniversityWest Lafayette, Indiana, United States
Grand Challenges Explorations
Infectious Diseases
1 May 2010

Christine Hrycyna and Jean Chmielewski of Purdue University in the U.S. will develop novel dimeric drugs designed to block a key protein in the malaria parasite that limits the accumulation of anti-malarials in the parasite's digestive system. By inhibiting this protein, this new therapy could eliminate drug resistance in malaria parasites.

Breastmilk shield to prevent HIV transmission

Gadi BorkowCupron, Inc.Richmond, Virginia, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Gadi Borkow of Cupron, Inc. in the U.S. will study the efficacy of using newly developed copper-oxide based filters that deactivate a wide range of viruses, including HIV-1, as a shield to enable HIV-infected mothers to breastfeed their infants without risking transmission of the virus.

Breeding the Epigenome in Crops

Sally MackenzieUniversity of Nebraska-LincolnLincoln, Nebraska, United States
Grand Challenges Explorations
Protecting Crop Plants
1 May 2012

Sally Mackenzie of the University of Nebraska-Lincoln in the U.S. will establish a strategy to exploit crop phenotype variations that are controlled by epigenetic changes for breeding. The strategy is to disrupt the MSH1 gene in millet and maize, releasing a large amount of variation derived from heritable epigenetic changes that can be used to select for abiotic and biotic stress tolerance.

Building a Mobile Midwives' Ultrasound

Beth KolkoUniversity of WashingtonSeattle, Washington, United States
Grand Challenges Explorations
Mothers and Newborns
1 Nov 2010

Beth Kolko of the University of Washington in the U.S. will build on recent research that has revealed that current portable ultrasound devices are often too complex for rural midwives in developing countries to use, and will develop instead a streamlined, inexpensive device with limited functionality, a simplified user interface, and a contextual help system. The prototype will be field tested with midwives in Uganda.

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