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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 H. pylori as a Diarrheal Vaccine Platform

Martin BlaserNew York UniversityNew York, New York, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Martin Blaser of the New York University School of Medicine in the U.S. proposes to engineer a harmless modification of H. pylori, a bacteria commonly found in the human stomach, to deliver antigens to protect against intestinal pathogens such as cholera and campylobacter. This modified H. pylori can only survive in the presence of an enzyme supplied in special drinking water, allowing those administering the vaccine to regulate its colonization.

Malaria Transmission Blocking Vaccines (TBV) Boosted By Natural Exposure

Kailash PatraUniversity of California, San DiegoSan Diego, California, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Kailash Patra of the University of California, San Diego in the U.S. will use proteomics to examine gametocyte, zygote, or ookinete surface proteins of the malaria parasite to test their reactivity to human serum collected from malaria endemic regions, and to identify new antigen candidates for malaria vaccines.

Transmission-Blocking Vaccine Based on Malaria Gamete Surface Protein

Nirbhay KumarTulane UniversityNew Orleans, Louisiana, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Nirbhay Kumar of Johns Hopkins University in the U.S. will use a technique called codon harmonization to fully and correctly express a complex malaria gamete surface protein. The sexual stages of malaria parasites have been shown to be particularly vulnerable to antibody targeting. This approach may be able to block the transmission of malaria in insect vectors.

Enhancing TB Vaccines with Gene Silencing

Jinhee LeeUniversity of MassachusettsWorcester, Massachusetts, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Jinhee Lee and Gary Ostroff of the University of Massachusetts Medical School in the U.S. will test the idea of delivering small interfering RNA (siRNAs) via glucan particles in an oral TB vaccine formulation. The team will utilize the siRNAs' ability to block immunosuppressive signaling and amplify the immune response.

Potentiating Mucosal Vaccines by RANKL Induction of M Cells

Ifor WilliamsEmory UniversityAtlanta, Georgia, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Ifor Williams of Emory University School of Medicine in the U.S. will test the theory that a newly characterized cytokine that triggers the development of M cells can be used as an adjuvant to boost immunity in mucosal surfaces and lead to greater uptake of vaccines.

Metabolic Engineering of Salmonella and Shigella Vaccines

Craig MoritaUniversity of IowaIowa City, Iowa, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Craig Morita of the University of Iowa in the U.S. will engineer Salmonella and Shigella vaccine vectors to overproduce an essential antigen to stimulate gamma delta T cells, to boost mucosal immune response against these enteric pathogens.

Targeted Oral Vaccines to Induce Cellular & Mucosal Immunity

Jennifer MaynardThe University of Texas at AustinAustin, Texas, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Jennifer Maynard and Nicholas Peppas of the University of Texas at Austin in the U.S. seeks to engineer proteins to be delivered by oral polymeric vaccine that specifically bind to receptors of M cells on the gut mucosa. By targeting these M cells, antigens can be introduced directly to the mucosal system, inducing a targeted, stronger immune response.

Vitamin A to Induce Gut Homing of Immune Cells

David SchwartzHackensack University Medical CenterHackensack, New Jersey, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

David Schwartz of Hackensack University Medical Center in the U.S. will test an intradermal injection that increases levels of vitamin A and blocks vitamin D3 metabolism. These important mechanisms can “educate” B cells to home to the gut and to make mucosal antibodies against many viruses, including HIV.

Intestinal Alkaline Phosphatase to Treat and Prevent Diarrhea

Madhu MaloGeneral Hospital CorporationBoston, Massachusetts, United States
Grand Challenges Explorations
Mucosal Immunity
1 Nov 2009

Madhu Malo of Massachusetts General Hospital/Harvard Medical School in the U.S. will investigate whether maintaining the normal intestinal commensal bacteria using oral supplementation of intestinal alkaline phosphatase (IAP), a small intestinal brush-border enzyme, will prevent or cure infection by pathogenic bacteria. A successful project would generate a universal prophylactic and therapeutic strategy against diarrheal diseases.

Novel Method Protecting Infants from HIV in Breast Milk

Renjie ChangLavaxPalantine, Illinois, United States
Grand Challenges Explorations
HIV Infection
1 Nov 2009

Renjie Chang of Lavax, Inc. in the U.S. has developed a natural food substance that reduces HIV viruses in the mother's milk, and will test it along with scientists at University of Toledo for its ability to block HIV transmission from mothers to infants.

Pre-Season Elimination of Malaria Infections

Sungano MharakurwaMalaria Institute at MachaChoma, Zambia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Sungano Mharakurwa of the Malaria Institute in Zambia proposes to take advantage of the “off-season” in regions affected by malaria. The team will identify asymptomatic carriers of the malaria parasite using a simple, non-invasive diagnostic tool using saliva samples which can be easily used by village community workers. Those individuals will be treated to eliminate the parasite before it can be transmitted during the rainy season, when malaria cases increase.

Inducing Autophagy in Dendritic Cells By DNA Delivery

Tanapat PalagaChulalongkorn UniversityBangkok, Thailand
Grand Challenges Explorations
Mucosal Immunity
9 Oct 2009

Tanapat Palaga of Chulalongkorn University in Thailand seeks to create a novel DNA vaccine delivery system that targets dendritic cells in GI mucosal tissues. Using chitosan nanoparticles to encapsulate DNA plasmid and protect it from stomach acid, this potential vaccine construct will contain both an antigen and an autophagy- inducing gene to enhance the vaccine's efficacy.

Eradication of Malaria through the Development of Host Directed Therapy

Simon FooteMenzies Research InstituteDarwin, Northern Territory, Australia
Grand Challenges Explorations
Malaria Eradication
8 Oct 2009

Simon Foote of the Menzies Research Institute at the University of Tasmania in Australia will use "forward genetic screening" approaches identify mutations that confer resistance after exposure to malaria parasites. The team will use this powerful information to develop drug therapies that target the human host and mimic these protective genetic effects.

Highly Sensitive, Low-Cost Malaria Test

Juan SantiagoStanford UniversityStanford, California, United States
Grand Challenges Explorations
Diagnostics
8 Oct 2009

Juan Santiago of Stanford University in the U.S. will develop small, disposable diagnostic device that utilizes isotachophoresis, a technique that separates charged particles, to concentrate a key biomarker of malaria parasites. The goal of this technique is to provide test results within three minutes at a sensitivity much greater than current tests, allowing for detection of malaria at much earlier stages of infection and in asymptomatic individuals.

Improving the Immunogenicity of HIV Envelope Glycoproteins

Michel GilbertNational Research Council of CanadaOttawa, Ontario, Canada
Grand Challenges Explorations
Vaccines
7 Oct 2009

Michel Gilbert of the National Research Council Canada will use the single-celled microorganism T. acidophilum to produce HIV proteins with unique sugar residues found only in archaebacteria such as T. acidophilum. By modifying these glycan structures to ones not recognized by humans, Gilbert hopes to elicit a stronger immune response against the virus.

Nanoparticle Mucosal Vaccine Platform from Eggshell Proteins

Allison FichtTexas A&M Health Science CenterCollege Station, Texas, United States
Grand Challenges Explorations
Mucosal Immunity
7 Oct 2009

Allison Ficht of Texas A&M Health Science Center in the U.S. will develop a new TB immunization delivery system based on the protein used by parasitic worms to seal their egg case. This “sticky coating” for nanoparticle vaccines could protect antigens during intranasal administration, affix them to the nasal mucosa and erode in a controlled way to slowly release antigens for enhanced immune response against tuberculosis.

Excreting HIV Using Antibodies

Edward DolkUtrecht UniversityUtrecht, Netherlands
Grand Challenges Explorations
Mucosal Immunity
6 Oct 2009

Edward Dolk of Utrecht University in the Netherlands proposes using two-sided antibodies, which bind to HIV and to transport receptors in the epithelium. Binding these receptors will cause excretion of the HIV particles outside of the body, thereby reducing viral load.

HIV Incidence Testing in Hair

Christopher PilcherUniversity of California San FranciscoSan Francisco, California, United States
Grand Challenges Explorations
Diagnostics
6 Oct 2009

Christopher Pilcher of the University of California, San Francisco in the U.S. will test the theory that HIV proteins, nucleic acids and antibodies to HIV can be detected in shafts of hair. This possible approach may provide a low-cost tool to determine the timing of HIV infection, which is essential to establish incidence rates in populations.

PlasmoTrack: Spatiotemporal Tracking of Malaria Parasites

Bryan GreenhouseUniversity of California San FranciscoSan Francisco, California, United States
Grand Challenges Explorations
Malaria Eradication
6 Oct 2009

Bryan Greenhouse of the University of California, San Francisco, will design a series of microsatellites, short DNA repeats which have variable lengths in different parasites, to track individual parasites in two regions close to malaria elimination. If successful, this approach will provide insight into parasite transmission networks and help to guide future malaria eradication efforts.

K+ Channel Blockers for Malaria Control

Lourival PossaniNational University of MexicoCuernavaca, Mexico
Grand Challenges Explorations
Malaria Eradication
5 Oct 2009

Lourival Possani of the Institute of Biotechnology at the National University of Mexico will investigate the antimalarial effects of scorpine, a newly identified peptide found in the venom of scorpions. The team will test scorpine's efficacy in blocking K+ channels used by malaria parasites to replicate in mosquitoes. Creating a new generation of malaria-resistant mosquitoes can aid in the eradication of the disease in humans.

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 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.

Microalgal Mediated Eradication of Malarial Mosquito Larvae

Richard SayreDonald Danforth Plant Science CenterSt. Louis, Missouri, United States
Grand Challenges Explorations
Malaria Eradication
1 Oct 2009

Richard Sayre of Donald Danforth Plant Science Center in the U.S. will develop and test a transgenic algae that delivers interference RNA (RNAi) elements to mosquito larvae when they feed on it. These RNAi will silence essential genes used by the larvae to develop, thus killing mosquitoes before they can transmit malaria.

Malaria Detection Using Earth's Magnetic Field

Viktor VeghUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Malaria Eradication
30 Sep 2009

Viktor Vegh of The University of Queensland in Australia will test the efficacy of using low-cost nuclear magnetic resonance technologies that take advantage of earth's magnetic field to detect malaria parasites. The team will examine blood samples to detect hemozoin, a waste product of malarial parasites, to determine the presence of malaria infection

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.

Mortalizing HIV – A Novel Method to Help Eradicate HIV

Reuben HarrisUniversity of MinnesotaMinneapolis, Minnesota, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

A high HIV mutation rate enables escape from powerful immune responses and anti-retroviral drugs. Reuben Harris of the University of Minnesota in the U.S. will test the hypothesis that HIV requires the human APOBEC3G protein to maintain a high mutation rate necessary for HIV survival. Inhibiting this protein may slow the mutation rate and make the virus more susceptible to immune responses.

Using Materials Science to Stop HIV Sexual Transmission

Patrick KiserUniversity of UtahSalt Lake City, Utah, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

Patrick Kiser of the University of Utah in the U.S. will design a vaginal gel that blocks HIV by becoming impermeable in response to the pH change induced by the presence of semen, and includes a polymer engineered to bind to HIV surface proteins to halt viral transport to susceptible tissues and HIV target cells. In this project's Phase I research, Kiser and his team engineered a synthetic polymer that has many of the properties of mucus, and demonstrated that the polymers slow or stops the movement of cells in the presence of semen. In Phase II, Kiser will focus on developing a pericoital contraceptive gel that will prevent the movement of spermatozoa into the uterus.

Zinc Finger Nucleases For in vivo Treatment of HIV Infection

Philip GregorySangamo BioSciences IncRichmond, California, United States
Grand Challenges Explorations
HIV Infection
1 May 2009

People born with a genetic mutation in their CCR5 gene are naturally resistant to HIV infection. Philip Gregory of Sangamo BioSciences, Inc. in the U.S. will use zinc finger nuclease technology to specifically disrupt the CCR5 gene as a new strategy to make people resistant to HIV.

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 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 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.

Development of a Synthetic Anti-Toxic Vaccine for Malaria

Louis SchofieldThe Walter and Eliza Hall Institute of Medical ResearchVictoria, Victoria, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

Louis Schofield of The Walter and Eliza Hall Institute in Australia will develop a synthetic saccharide-conjugated vaccine that would provide immunity against GPI, a toxin produced by the malaria parasite that is a major determinant in the severity and fatality of the disease. This project's Phase I research demonstrated preclinical safety and efficacy of a synthetic anti-toxin vaccine for malaria, showing that the oligosaccharide target was conserved across all malaria species and life stages. In Phase II, Schofield is extending the preclinical evaluation of efficacy of this candidate vaccine against other species and life stages.

Liposomal Dendiritc-Cell (DC)-Targeted Vaccines for TB

Ines AtmosukartoLipotek Pty LtdCanberra, Australian Capital Territory, Australia
Grand Challenges Explorations
Vaccines
1 May 2009

Ines Atmosukarto of Lipotek Pty Ltd. in Australia proposes to develop a novel TB vaccine utilizing synthetic “nano-sacs” called liposomes that carry TB antigens and are anchored with a self-adjuvanting protein that binds to and stimulates dendritic cells.

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.

MicroCubes as Vaccines for the Developing World

Fasseli CoulibalyMonash UniversityClayton, Victoria, Australia
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Fasséli Coulibaly of Monash University in Australia will design a vaccine platform based on protein crystals (MicroCubes) produced by insect viruses to produce new and more potent vaccines with increased stability, obviating the need for refrigerated storage. The crystal structure will be engineered to present multiple antigens that will then be tested for their ability to induce an effective immune response. In Phase I, a proof-of-concept study was performed to establish MicroCubes as a promising vaccine platform, focusing on production versatility, potential vaccine delivery routes, and efficacy for inducing an immune response in mice. In Phase II, they will investigate the broader potential of MicroCubes as a generic vaccine platform that can be used to deliver a wide range of antigens, and will use it to develop a candidate vaccine against HIV.

Prevention of Visceral Leishmaniasis Disease in Asymptomatic VL Patients

Dinesh MondalInternational Centre for Diarrhoeal Disease Research, BangladeshDhaka, Bangladesh
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Because malnutrition, micronutrient deficiency and parasitic worm infection are all major risk factors for developing visceral leishmaniasis, Dinesh Mondal of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) will study if VL development can be prevented in asymptomatic patients through nutritional supplements of vitamin A, zinc and iron, as well as anti-helminth treatment.

Reducing Risk of ALRI by Improving Indoor Air Pollution

Golam RabbaniInternational Centre for Diarrhoeal Disease Research, BangladeshDhaka, Bangladesh
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Golam Rabbani of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) will study the effects that a new model of indoor cooking stove with concealed combustion chambers and ventilation chimney has in reducing indoor air pollution and subsequently, reducing acute lower respiratory infections and TB in children.

Large-Scale MHC Epitope Analysis for Vaccine Development

Gustavo Fioravanti VieiraUniversidade Federal do Rio Grande do SulPorto Alegre, Rio Grande do Sul, Brazil
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Gustavo Fioravanti Vieira of Universidade Federal do Rio Grande do Sul in Brazil will create 3-D computer models of viral epitopes anchored to major histocompatibility complex (MHC) molecules associated with different MHC alleles to search for “generalist” epitopes. Such epitopes can be used to develop viral vaccines that are effective against a broad spectrum of pathogens.

Increasing Vaccination Efficacy with ACE Inhibitors

Julio ScharfsteinUniversidade Federal do Rio de JaneiroRio de Janeiro, Rio de Janeiro, Brazil
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Julio Scharfstein of Universidade Federal do Rio de Janeiro in Brazil will study whether a pre-dose of captopril, an established angiotensin-converting enzyme (ACE) inhibitor and anti-hypertension drug, can increase the potency of vaccines by increasing the activation of dendritic cells.

Immune Reinforcing Attenuated Whole-Sporozoite as Vaccine

Guang-hong TanHainan Provincial Key Laboratory of Tropical MedicineHaikou, China
Grand Challenges Explorations
Vaccines
1 May 2009

Guang-hong Tan of Hainan Provincial Key Laboratory of Tropical Medicine in China seeks to create a next-generation malaria vaccine by deleting a gene responsible for parasite development in the liver adding a new gene which attracts dendritic cells to the infection site. Using this modified sporozoite in a vaccine could produce a limited infection that, at the same time, induces a strong immune response against malaria.

Generation of Influenza-Resistant Chicken by Triple Combination Lentiviral Vector-mediated Genetic Modification

Chen YangchaoThe Chinese University of Hong KongHong Kong, China
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Chen Yangchao of the Chinese University of Hong Kong proposes developing a lentiviral vector that targets the entry and replication of influenza viruses in domestic chickens. The team plans to test the ability of these modified chickens to be resistant to various influenza viruses in an effort to reduce the frequency of flu epidemics in poultry and, ultimately, in humans.

Vaccine Discovery by Mapping Quasi-species Sequence Space

Marco VignuzziInstitut PasteurParis, France
Grand Challenges Explorations
Infectious Diseases
1 May 2009

In organisms that have extreme mutation rates, such as RNA viruses, quasispecies are highly diverse genotypes that may drastically differ from the general population and often become less viable as they continue to mutate. Using new deep sequencing technology, Marco Vignuzzi of the Pasteur Institute in France hopes to identify such RNA viruses that have managed to retain attenuated strains in order to study these genotypes for possible use in the development of viral vaccines.

Rapid Urine-Based Dipstick Test for Diagnosis of Malaria

Uri McKakpoUniversity of GhanaAccra, Ghana
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Uri Selome McKakpo of the University of Ghana will develop and test a rapid dipstick test that utilizes monoclonal antibodies to detect parasite antigens present in urine of infected individuals. Using this technology, the team hopes to create a new diagnostic test for malaria that requires minimal training to use and does not depend on invasive blood samples.

How to Break B Tolerance and Induce HIV-Protective Antibodies to CCR5

Lucia LopalcoSan Raffaele Scientific InstituteMilano, Italy
Grand Challenges Explorations
Vaccines
1 May 2009

HIV uses the CCR5 co-receptor protein found in mammals as a major pathway to enter target cells. Because some patients who are exposed, yet resistant, to the virus, or have HIV but do not ever progress to AIDS can exhibit the presence of CCR5 internalizing antibodies, Lucia Lopalco of the San Raffaele Scientific Institute in Italy will attempt to generate “anti-self” antibodies against CCR5 to knock out protein's co-receptor and effectively block HIV entry.

Host Targets in Mtb Infection

Nigel SavageLeiden University Medical CenterLeiden, Netherlands
Grand Challenges Explorations
Drug Resistance
1 May 2009

Because tuberculosis manipulates host cells to resist the immune response and current drug therapies, Nigel Savage of Leiden University Medical Center in the Netherlands will utilize RNAi analysis to identify the essential pathways used by the bacteria to modify its host cell. By discovering these pathways, novel therapies can be developed to counteract this host manipulation without directly targeting the pathogen and causing the development of resistance.

Robotic Health Assistant for Rational Management of Fevers among Nomads

Oladele AkogunCommon Heritage FoundationJimeta-Yola, Nigeria
Grand Challenges Explorations
Drug Resistance
1 May 2009

Oladele Akogun of the Common Heritage Foundation in Nigeria seeks to develop a “fever kit” for use among nomadic populations to help them accurately diagnose and treat fevers in a way that reduces mortality and drug resistance. The device will be equipped with simple diagnostic tools and prerecorded treatment instructions in the native language to help nomadic caregivers distinguish between malaria and other causes of fevers, and will also contain drug treatments appropriate to the diagnosed illness.

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.

Development of Indoor Spray to Control Malaria Transmission

Walter FockeUniversity of PretoriaPretoria, South Africa
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Because DDT is the only insecticide that remains effective for more than a year, Walter Focke of the University of Pretoria in South Africa will investigate how insecticides degrade when applied on an indoor surface. Focke will then study whether combining the insecticide with paint to create a “whitewash” can mitigate this disintegration and enhance stability.

Latency in M. tuberculosis – A Highly Dynamic Phenomenon

Maria LermLinköping UniversityLinkoping, Sweden
Grand Challenges Explorations
Tuberculosis Latency
1 May 2009

Maria Lerm of Linkoping University in Sweden will test her hypothesis that TB latency is a dynamic process in which a portion of the bacilli, when ingested by macrophages, trigger a genetic program where bacteria cycle between active and latent phases. Understanding whether this dynamic cycle exists could give new insights into maintaining or targeting the latent bacteria, which is the major reservoir of TB globally.

Drug-Induced Differentiation of Trypanosomes Leads to Lysis

Reto BrunSwiss Tropical & Public Health InstituteBasel, Switzerland
Grand Challenges Explorations
Drug Resistance
1 May 2009

Reto Brun (Swiss Tropical and Public Health Institute) and Isabel Roditi (University of Bern) in Switzerland seek to identify small molecules that prematurely induce African trypanosomes, which are parasites that cause fatal sleeping sickness, to differentiate into the life stages necessary for transmission of the parasite. Forcing this transformation within the mammalian host could be the basis for new methods to kill trypanosomes, and this concept might be applied to other vector-borne disease . In this project’s Phase I research, Brun and Roditi developed a whole-cell assay to identify small molecules that stimulate early differentiation of African trypanosomes. In Phase II, they will perform high-throughput screens for such small molecules, validate active molecules in a suite of assays, and study them in a mouse model of infection.

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