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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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Challenges: Drug Resistance
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A Lexicon of HIV-RNA Interactions

Alice Telesnitsky, University of Michigan (Ann Arbor, Michigan, United States)
May 1, 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 Novel Bactericidal Protein Found in Milk

Anders Hakansson, The Research Foundation for The State University of New York (Albany, New York, United States)
May 1, 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 Way of Targeting TB using Aptamers and Nanotechnology

Boitumelo Semete, Council for Scientific and Industrial Research (Pretoria, South Africa)
May 1, 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.

Anti-TB Drugs That Limit Evolution of Resistance

Gerald Smith, Fred Hutchinson Cancer Research Center (Seattle, Washington, United States)
May 1, 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.

Biosynthetic Immunotargeting for Pneumococcal Treatment

David Spiegel, Yale University (New Haven, Connecticut, United States)
May 1, 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.

Combating Antibiotic Resistance in Tuberculosis

Krishna Kodukula, SRI International (Menlo Park, California, United States)
May 1, 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.

Drug-Induced Differentiation of Trypanosomes Leads to Lysis

Reto Brun, Swiss Tropical & Public Health Institute (Basel, Switzerland)
May 1, 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.

Dual-Mode Binding Inhibitors to Suppress P. falciparum DHFRs

Bongkoch Tarnchompoo, National Center for Genetic Engineering and Biotechnology (Pathumthani, Thailand)
May 1, 2009

Bongkoch Tarnchompoo of the National Center for Genetic Engineering and Biotechnology in Thailand will attempt to develop and test a novel drug that binds to the two pathways used by the DHFR enzyme in P. falciparum to mutate. By tethering these active sites, the dual-binding drug will suppress the development of resistance to anti-malarial drugs.

Host Targets in Mtb Infection

Nigel Savage, Leiden University Medical Center (Leiden, Netherlands)
May 1, 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.

Killing T. brucei by RNA Aptamer-Mediated Immobilization

Arthur Günzl, University of Connecticut Health Center (Farmington, Connecticut, United States)
May 1, 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.

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View the Grand Challenges partnership network

The Bill & Melinda Gates Foundation is part of the Grand Challenges partnership network. Visit www.grandchallenges.org to view the map of awarded grants across this network and grant opportunities from partners.