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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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Small Molecule Antimicrobial Peptide Mimics as Antimalarials

Doron GreenbaumUniversity of PennsylvaniaPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

Antimicrobial peptides (AMPs) are essential components of the innate immune system that provides resistance to a variety of pathogenic organisms by selectively lysing, or bursting, cellular membranes of invading pathogens. Doron Greenbaum of the University of Pennsylvania in the U.S. will test whether small molecules that mimic the natural AMPs can selectively kill the parasite that causes malaria. Such an approach could reduce costs of production as well as limit the emergence of drug resistance.

Targeting Erythrocyte Determinants of Malaria Infection

Manoj DuraisinghHarvard UniversityCambridge, Massachusetts, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

Manoj Duraisingh of the Harvard School of Public Health in the U.S. will use RNAi screening to identify critical determinants in human red blood cells (erythrocytes) that are required for invasion and growth of the malaria parasite, Plasmodium falciparum. In this project's Phase I research, Duraisingh's group developed a RNAi- based approach for genetic analysis of the erythrocyte in vitro, and demonstrated that the major surface protein Glycophorin A is required for efficient invasion by some strains of P. falciparum. The group made progress in the development of a high-throughput RNAi screen, which in Phase II of the project Duraisingh hopes will identify those essential erythrocyte determinants that are most amenable to the development of host-targeted drug therapies.

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.

Killing T. brucei by RNA Aptamer-Mediated Immobilization

Arthur GünzlUniversity of Connecticut Health CenterFarmington, Connecticut, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

T. brucei, the parasite that causes sleeping sickness, must continuously swim forward in human blood to evade immune responses. Arthur Günzl of the University of Connecticut Health Center in the U.S. will attempt to develop serum-stable RNA molecules to immobilize the parasite by interrupting the mechanism driving parasite motility.

Combating Antibiotic Resistance in Tuberculosis

Krishna KodukulaSRI InternationalMenlo Park, California, United States
Grand Challenges Explorations
Drug Resistance
1 May 2009

To test the theory that certain metabolic pathways essential to the survival of bacteria are immutable and therefore promising targets of drug therapy, Krishna Kodukula and colleagues at SRI International in the U.S. will identify peptides that bind key metabolites of M. tuberculosis, and test their ability to kill the bacteria.

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.

Primaquine Revisited – Safety and Efficacy of PQ Isomers

Larry WalkerUniversity of MississippiUniversity, Mississippi, United States
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Larry Walker of the University of Mississippi in the U.S. will test an innovative approach to mitigate the toxicity of primaquine, a promising and powerful malaria drug. Walker will separate the drug into two components, called isomers, to see if a single form retains the ability to eliminate the malaria parasite in its latent liver stages and the mature gametocytes while reducing toxic side effects.

Novel Class of Long-Range Olfactory Repellents for Anopheles

Anandasankar RayUniversity of California, RiversideRiverside, California, United States
Grand Challenges Explorations
Malaria Eradication
1 May 2009

CO2 present in exhaled air is used by Anopheles mosquitoes to find their human hosts. Anandasankar Ray of University of California-Riverside plans to identify odors that inhibit the mosquito's CO2- sensitive olfactory neurons, and design long-distance repellents that block the ability of mosquitoes to detect humans and protect large areas.

Targeting TRP Channel Heat Receptors to Disrupt An. gambiae Host Seeking

Guirong WangVanderbilt UniversityNashville, Tennessee, United States
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Guirong Wang and colleagues at Vanderbilt University in the U.S. have recently identified key sensory heat receptors used by mosquitoes to target hosts. Wang will use these proteins as molecular targets to develop insect repellents and masking agents that block or hyper-stimulate these receptors and reduce the ability of the vectors to find hosts and spread disease.

Using Bacteria to Contain the Spread of Malaria

Marcelo Jacobs-LorenaJohns Hopkins UniversityBaltimore, Maryland, United States
Grand Challenges Explorations
Malaria Eradication
1 May 2009

Marcelo Jacobs-Lorena, of the Johns Hopkins School of Public Health in the U.S. proposes to modify bacteria that naturally inhabit the mosquito midgut to secrete proteins that interfere with the development of the malaria parasite in the mosquito that is necessary for malaria transmission.

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