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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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Complement-Based Antibiotic Microbeads

Todd SulcheckGeorgia Tech Research CorporationAtlanta, Georgia, United States
Grand Challenges Explorations
Infectious Diseases
31 Mar 2010

Todd Sulchek of Georgia Tech and David White of the Centers for Disease Control in the U.S. will develop and test the ability of a bi-functional microbead to stimulate the innate immune response. On one hemisphere, the microbead will display targeting antibodies that will bind to pathogens, and on the other hemisphere the microbead will feature Fc fragments that activate the complement system and recruit immune cells to destroy the captured pathogen.

Detecting Pathogenic Microbes by a "Microbial Litmus Strip"

Liaohai ChenRush University Medical CenterChicago, Illinois, United States
Grand Challenges Explorations
Diagnostics
1 Apr 2010

Liaohai Chen of Rush University Medical Center in the U.S. will develop nanoparticles which react to the presence of pathogenic microbes by releasing encapsulated substances that quickly amplify the binding signals. These nanoparticles can be placed on the tip of a litmus strip as a colorimetric assay to indicate the presence and concentration of pathogens.

Compact Disc Diagnostics for Early Disease Detection

Robert DunnUniversity of Kansas Center for ResearchLawrence, Kansas, United States
Grand Challenges Explorations
Diagnostics
1 Apr 2010

Robert Dunn and colleagues at the University of Kansas in the U.S. will develop a diagnostic tool for the early detection of disease that employs writable compact discs that can be read in conventional computer disc drives. Microfluidic structures and immobilized antibodies will be fabricated onto small sections of a compact disc, along with enzymes that produce a reflective “silvering” surface upon recognition of target biomarkers. These changes in reflection can be read by any conventional CD drive, allowing for diagnosis using laptops in low resource settings.

Safe, Cost-effective, and Functional Strategy for Immune Intervention

Sunil JoshiUniversity of Oklahoma Health Sciences CenterOklahoma City, Oklahoma, United States
Grand Challenges Explorations
Infectious Diseases
2 Apr 2010

Sunil Joshi of the University of Oklahoma Health Sciences Center in the U.S. will study the efficacy of delivering a non-invasive low-voltage electric wave pulse in the vicinity of lymphoid tissues to stimulate the activation and maturation of dendritic cells. If successful, this would be a method of boost long-term immunity.

Defeating Insect-Borne Diseases Using Atomic-Level Structure

Filippo ManciaColumbia UniversityNew York, New York, United States
Grand Challenges Explorations
Infectious Diseases
5 Apr 2010

Filippo Mancia of Columbia University in the U.S. will perform crystallization experiments on a key olfactory receptor used by mosquitoes to detect humans. The aim of these studies is to determine at an atomic level the conserved regions on the olfactory receptor in order to develop drug therapies to block these receptors. This project's Phase I research generated diffraction quality crystals of this targeted mosquito olfactory receptor, and in Phase II, the team will optimize the crystal to determine the structure of the receptor and how it binds to small molecule anti-malarial compounds. Visualizing this interaction in atomic detail will aid in the optimization of these compounds as highly effective insect repellents.

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.

Readerless Point of Care Diagnostics for Viral Load

Roozbeh GhaffariDiagnostics For AllCambridge, Massachusetts, United States
Grand Challenges Explorations
Diagnostics
7 Apr 2010

Roozbeh Ghaffari, Patrick Beattie, Jason Rolland, and Jeff Carbeck of Diagnostics For All & MC10 Inc. in the U.S. sought to develop disposable paper-based diagnostics devices embedded with optoelectronics, allowing quantitative colorimetric analysis for HIV viral load monitoring. This platform addresses practical limitations of current image capture methodologies and eliminates the need for external readers. In Phase I, they built a point-of-care detection device by incorporating ultrathin, flexible electronics onto a paper substrate, and tested its ability to quantify viral load by measuring levels of HIV p24 antigen. Having improved the sensitivity of their colorimetric assay, in Phase II Christina Swanson and her team will develop and test a new class of multiplexed, paper-microfluidic devices called electronics-enabled-Point of Care (E-POC) that can quantitate micronutrient markers from whole blood and transmit the data wirelessly to existing mobile phones equipped with near-field communication.

Towards Treatment of Pediatric Tuberculosis with IFN-?

Jean-Laurent CasanovaRockefeller UniversityNew York, New York, United States
Grand Challenges Explorations
Infectious Diseases
9 Apr 2010

Jean-Laurent Casanova of The Rockefeller University in the U.S. seeks to identify single gene mutations that are critical to immunity against bacterial infections. By characterizing these mutations, Casanova could provide insight into a genetic basis for the susceptibility of some children to Tuberculosis, that could inform a recombinant IFN-y drug therapy.

Viral Self-Destruct Sequences: A Novel Vaccine Technology

David JansMonash UniversityClayton, Victoria, Australia
Grand Challenges Explorations
Infectious Diseases
12 Apr 2010

Gregory Moseley, Stephen Rawlinson and David Jans at Monash University in Australia will engineer a live virus with a self-destruct sequence for use in a vaccine. This virus would be identical to a wild-type virus, but contain destabilizing domains fused to key proteins that can be regulated to first allow the virus to replicate and induce an immune response, and then be destroyed.

Simple Early Breath Diagnosis of Pneumococcal Pneumonia

Hongyue DangChina University of Petroleum (East China)Qingdao, China
Grand Challenges Explorations
Diagnostics
12 Apr 2010

Hongyue Dang, of China University of Petroleum (East China) will research whether early-stage pneumonia infection produces specific biomarkers that can be detected in a breath analysis. If so, Dang will produce and test a prototype breath sensor device that can be used in low-resource settings to capture and analyze these signature chemical compounds as a method to diagnose pneumonia.

Sentinel Commensals for in situ Temporal Protection against Bacterial Diarrheas

Jun ZhuUniversity of PennsylvaniaPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Infectious Diseases
12 Apr 2010

Jun Zhu and Mark Goulian of the University of Pennsylvania in the U.S. propose to use phage display technology to engineer a commensal “sentinel” bacteria that be introduced into the gut flora. Bacterial toxins would be detected by the sentinel commensal, which would bind to the toxin and express enzymes to destroy it.

Vaccine Cytokine Trap Technology to Induce Immunity

Charani RanasingheThe Australian National UniversityActon, Australian Capital Territory, Australia
Grand Challenges Explorations
Mucosal Immunity
13 Apr 2010

Charani Ranasinghe of The Australian National University will test a new vaccine technology that modulates a host cytokine response to HIV vaccines. If successful, this “cytokine trap” technology may also enhance T-cell mediated immunity to other vaccine antigens, such as Tuberculosis.

Low-Cost, Rapid, Multiplexed Detection of TB

Vineet GuptaMiami Institute of Renal MedicineMiami, Florida, United States
Grand Challenges Explorations
Diagnostics
13 Apr 2010

Vineet Gupta of the University of Miami in the U.S. will develop a computational model to identify new DNA sequences in the Tuberculosis bacterium that can be used as biomarkers, and then employ zinc-finger tags to detect the identified DNA sequence in a diagnostic test.

Nano-Dumbbells for Single-Molecule Diagnostics from Saliva

Krassen DimitrovUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Diagnostics
14 Apr 2010

Krassen Dimitrov of the University of Queensland in Australia will develop a new diagnostic test which utilizes nanoparticles which bind to specific biomarkers in saliva that are present during infection. With a magnetic particle binding to one side of a biomarker and a non-magnetic particle attaching to the other side, a visual “dumbbell” is formed, which can be detected using a low-cost magnetic reader.

Inducing Mucosal Immunity Using Retinoids & Oral Vaccines

Paul KellyQueen Mary & Westfield CollegeLondon, United Kingdom
Grand Challenges Explorations
Mucosal Immunity
15 Apr 2010

Paul Kelly of Queen Mary, University of London in the United Kingdom and the University of Zambia will test the idea that retinoic acid (a form of vitamin A) given with an oral vaccine will boost the mucosal immune response. If successful, vitamin A derivatives could be used as adjuvants for oral vaccines that target childhood diarrhea. In this project’s Phase I research, Kelly was able to demonstrate that retinoic acid enhances gut IgA responses to an oral typhoid vaccine in Zambian adults. In Phase II Kelly seeks to define the mechanisms by which retinoic acid works as an adjuvant, its optimal dosage, whether it works with other vaccines, and whether the effect can be generalized to children in tropical populations with varying degrees of growth impairment.

Noroviral Replicon:VLP for Gut Mucosal Immunity

Alec SutherlandArizona State UniversityTempe, Arizona, United States
Grand Challenges Explorations
Mucosal Immunity
15 Apr 2010

Alec Sutherland of Arizona State University in the United States will develop and test a vaccine delivery system that uses Norovirus virus-like particles (VLPs) to deliver desired antigens directly to the gut mucosa. The self-replicating RNA in the VLP will not only encode those antigens, it will also act as an adjuvant by activating several signaling pathways for an enhanced and sustained immune response.

Cost-Effective Testing of Blood Samples Using Cellphones

Aydogan OzcanUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
Diagnostics
20 Apr 2010

Aydogan Ozcan of the University of California, Los Angeles in the U.S. will test the feasibility of a lens-free cell phone microscope for rapid, automated and accurate diagnosis of malaria in field settings. This on-chip cell phone microscope is based on digital holography and does not require any lenses, lasers or other bulky components making it extremely cost-effective and compact.

Separation of Malaria-Infected Erythrocytes From Whole Blood

George WhitesidesHarvard UniversityCambridge, Massachusetts, United States
Grand Challenges Explorations
Diagnostics
20 Apr 2010

George Whitesides of Harvard College in the U.S. will develop a novel low-cost device that can detect the presence of malaria-infected red blood cells in a drop of blood using an egg beater as a centrifuge. The blood drop is added to a short polyethylene tube filled with three polymer solutions, each of which have different densities and do not mix. The tube is connected to an egg beater and rotated for five minutes, allowing the blood to separate into layers of healthy erythrocytes, infected erythrocytes and white blood cells, detectable in the spaces between the polymer layers.

Unleashing Protein Disaggregases to Prevent HIV Infection

James ShorterUniversity of PennsylvaniaPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Infectious Diseases
22 Apr 2010

James Shorter of The University of Pennsylvania in the U.S. will engineer enzymes that disassemble protein fibrils found in semen, which are known to allow for the transmission of HIV infection. The ability to reverse fibril formation could block sexual transmission of HIV and provide a new weapon against the global HIV/AIDS pandemic.

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.

Exhaled Diagnosis of MTb

Simon SpivackAlbert Einstein College of Medicine of Yeshiva UniversityBronx, New York, United States
Grand Challenges Explorations
Diagnostics
23 Apr 2010

Simon Spivack, Albert Einstein College of Medicine in the U.S. will test the theory that DNA of the Tuberculosis bacterium can be detected in exhaled breath. The team will capture exhaled breath condensate samples via a non-invasive device and use nucleic acid amplification to detect the presence of mycobacteria.

Stable Protein Capture Agents with Antibody-like Properties

James HeathCalifornia Institute of TechnologyPasadena, California, United States
Grand Challenges Explorations
Diagnostics
30 Apr 2010

James Heath of the California Institute of Technology in the U.S. will build stable, low-cost protein capture agents to target proteins. If successful, these agents could replace expensive and unstable monoclonal antibodies that are currently needed for diagnostic tests.

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.

Women-Controlled Contraception That Also Prevents HIV

Guiying NiePrince Henry's Institute of Medical ResearchClayton, Victoria, Australia
Grand Challenges Explorations
Contraceptive Technologies
1 May 2010

Guiying Nie of Prince Henry's Institute of Medical Research in Australia will test whether a peptide inhibitor that has been shown to inhibit protein processing critical to HIV transmission can also be used to prevent embryo implantation in the uterus. If successful, the peptide could be used as a non-hormonal contraceptive delivered as a vaginal application, which also protects against HIV.

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

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