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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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Engineered TALE Nucleases for Broad-Spectrum Resistance Against Cassava-Infecting Geminiviruses

Savithramma Dinesh-KumarUniversity of California, DavisDavis, California, United States
Grand Challenges Explorations
Protecting Crop Plants
23 Oct 2012

Savithramma Dinesh-Kumar of the University of California, Davis, along with David Segal of the University of California, Davis and Vincent Fondong of Delaware State University in the U.S., seek to design custom TALE nucleases that target and cleave critical regions of DNA from cassava-infecting geminiviruses (CMGs) to completely inactivate the viruses. CMGs are a major threat to cassava production in Africa, and targeted nucleases could be used to engineer CMG resistance into staple African cassava varieties to promote regional food security.

Neuropeptides as Transgenic Nematicides

Johnathan DalzellQueen's University BelfastBelfast, United Kingdom
Grand Challenges Explorations
Protecting Crop Plants
22 Oct 2012

Johnathan Dalzell of Queen's University Belfast in the United Kingdom will improve food crop productivity particularly for small hold subsistence farmers by reducing the losses caused by pathogenic nematode worms, which are estimated to cost around $125 billion per year globally. These pathogenic worms absorb small proteins called neuropeptides from their external environment directly into their central nervous system, which can influence their movement and sensory behavior. They will exploit this process to destroy the worms. In Phase I, they identified two neuropeptide genes in the root knot nematode (RKN) Meloidogyne incognita, which is a serious pathogen of many crop types. They also exposed infectious stage nematodes to a selection of neuropeptides and found 11 that inhibited their movement towards plant roots, and 13 that protected a crop plant from infection. Finally, they established protocols to genetically modify crops to express and secrete the neuropeptides. In Phase II, they will develop knowledge and methods to produce transgenic plantain, which is a staple food crop of sub-Saharan Africa and a target of five major plant parasitic nematode species, to secrete multiple candidate neuropeptides, and test their resistance to infection.

Creating a Decision Aid to Better Forecast Vaccine Delivery

Roger MillerLogistics Management InstituteMcLean, Virginia, United States
Grand Challenges Explorations
Immunization Systems
22 Oct 2012

Roger Miller and colleagues at the Logistics Management Institute in the U.S. propose to develop a software-based prototype modeling tool that allows vaccine program managers to lower total delivered costs by analyzing all of the clinical and logistical factors that determine the cost per viable vaccine dose administered. The prototype could be developed as a fully deployable software product with associated training, reporting, and analysis capability.

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.

Enhancing Identification of Malaria Drug Targets

Jacquin NilesMassachusetts Institute of TechnologyCambridge, Massachusetts, United States
Grand Challenges Explorations
Malaria Drugs
22 Oct 2012

Jacquin Niles of the Massachusetts Institute of Technology in the U.S. is developing a method to switch individual genes on and off in the malaria-causing parasite Plasmodium falciparum for evaluating candidate and existing antimalarial drugs. In Phase I, they built and tested a scalable TetR-aptamer system for rapidly and easily manipulating gene expression in the parasite genome, and showed that it could be used to validate the target of a 4-aminoquinoline antimalarial drug. In Phase II they will use the system to produce a reference panel of over 150 stable parasite lines in which target genes of interest can be conditionally regulated. This resource, which can be expanded, will be valuable for investigating basic parasite biology as well as for drug development. They will use these lines to screen known and candidate antimalarial compounds to identify their targets and help improve their activity.

Polysaccharide-GMMA Particle Vaccines for Global Health

Calman A. MacLennanNovartis Vaccines Institute for Global HealthSienna, Italy
Grand Challenges Explorations
Global Health Solutions
19 Oct 2012

Calman A. MacLennan of Novartis Vaccines Institute for Global Health in Italy will develop a technology platform for the production of highly immunogenic and affordable polysaccharide vaccines. The platform will produce bacterial polysaccharides linked to outermembrane GMMA particles, rather than to carrier proteins, that will act as adjuvants for an enhanced antibody response.

The Transfer Cells of the Maize Seed, an Anti-Fungal Barrier

Gregorio HuerosUniversity of AlcaláAlcalá de Henares, Spain
Grand Challenges Explorations
Protecting Crop Plants
19 Oct 2012

Gregorio Hueros of Universidad de Alcala in Spain will engineer maize kernels to increase the expression of anti-fungal genes in the transfer cell layer, which transports nutrients and protects filial tissues in the adjacent growing seeds. This could boost the ability of these cells to protect the grain against invasion by pathogens such as mycotoxin-producing fungi.

Mucus-Penetrating Particles to Improve Mucosal TB Vaccines

Eric NuermbergerJohns Hopkins University School of MedicineBaltimore, Maryland, United States
Grand Challenges Explorations
Global Health Solutions
19 Oct 2012

Eric Nuermberger and Justin Hanes of Johns Hopkins University in the U.S. propose to encapsulate vaccine components into nanoparticles that can slip through the mucus barriers lining the respiratory and gastrointestinal tracts to deliver their payload to cells responsible for immune responses. This technology may result in more effective and better tolerated oral and inhaled tuberculosis vaccines.

Microfluidic Platform for Rapid Drug Resistant Screening

Daniel IrimiaGeneral Hospital CorporationBoston, Massachusetts, United States
Grand Challenges Explorations
Malaria Drugs
19 Oct 2012

Daniel Irimia and Anh Hoang of Massachusetts General Hospital in the U.S. seek to develop a microfluidic device that can be used to screen anti-malarial drugs for the development of drug resistance with single cell resolution. The device will be validated using a subset of anti-malarial compounds from the Malaria Box. The ability to monitor single cells for resistance will greatly reduce the time needed to screen drugs for acquired resistance, allowing for much earlier and more accurate assessment of effective drugs to control and eradicate malaria.

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.

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