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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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A Novel Antimicrobial Delivery System

George O'TooleDartmouth CollegeHanover, New Hampshire, United States
Grand Challenges Explorations
Drug Resistance
1 Oct 2008

George O'Toole, a microbiologist at Darmouth Medical School, and Mark Grinstaff, a biomedical engineer and chemist at Boston University, will work to develop an expansile nanoparticle, packed with high concentrations of antibiotics, which would expand and release their content when internalized by host cells. The hope is that more precise delivery of high concentrations of antimicrobial agents, in single or combination therapies, will reduce the development of resistance.

A Novel Approach of Creating an Attenuated Pneumonia Vaccine

Vijay PancholiOhio State University Research FoundationColumbus, Ohio, United States
Grand Challenges Explorations
Vaccines
1 Nov 2009

Vijay Pancholi of The Ohio State University Research Foundation in the U.S. will attempt to attenuate the S. pneumonia bacteria by altering export of the GAPDH enzyme, a function thought to be essential to the bacteria's survival. Preventing export of this key enzyme will decrease bacterial virulence, allowing the attenuated strain to be used for development an affordable live vaccine for pneumococcal pneumonia.

A Novel Approach to Prevent or Cure HIV Infection

Karthikeyan KandavelouPondicherry Biotech Pvt LtdPondicherry, , India
Grand Challenges Explorations
HIV Infection
1 Oct 2008

People born with a natural resistance to the HIV virus have a genetic mutation in the CCR5 gene. Karthikeyan Kandavelou of Pondicherry Biotech Pvt. Ltd. in India will attempt to achieve targeted disruption of CCR5 genes, making an important first step in a new strategy to make people permanently resistant to HIV.

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.

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 Novel Structure-Based Model for the Prediction and Exploitation of Resistance Mutations

Ryan LilienUniversity of TorontoToronto, Ontario, Canada
Grand Challenges Explorations
Drug Resistance
1 Oct 2008

Dr. Ryan Lilien of the University of Toronto in Canada will work to computationally model the structural and functional effects of point mutations on a target protein's active site. With the development of predictive models of pathogen evolution and the spread of resistance, this information can be used to guide drug development and optimization.

A Novel Vaccination Strategy for Cutaneous Leishmaniasis

Jesus ValenzuelaNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
Infectious Diseases
1 May 2009

Because Leishmania is transmitted to humans when sand flies feed on humans, Jesus Valenzuela of the National Institutes of Health in the U.S. proposes to develop a novel vaccine against salivary proteins of sand flies with the aim to induce a strong immune response against the parasite.

A Novel Virulence-Associated Malaria Drug Target

Paul GilsonBurnet InstituteMelbourne, Victoria, Australia
Grand Challenges Explorations
Malaria Eradication
1 Nov 2009

Paul Gilson of Macfarlane Burnet Institute for Medical Research and Public Health in Australia will study the function of a newly discovered malaria parasite mechanism that exports proteins into host red blood cells in an effort to develop compounds that block this transfer and inhibit parasite growth.

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.

A Novel, Simple Method to Find Inexpensive Drugs for Preeclampsia Treatment

Timothy LyonsQueen's University BelfastBelfast, United Kingdom
Grand Challenges for Development
Saving Lives at Birth
15 Nov 2014

Preeclampsia (PE) is a disease without targeted treatments. We propose a simple strategy to solve this problem: we will establish a cell-based assay to screen clinically-available, mostly generic and inexpensive, drugs that may have a therapeutic effect on PE. To do this, we will utilize new scientific knowledge, showing that anti-angiogenic factors released from the placenta trigger maternal vascular injury essential for the development of PE. The drugs to be screened are chosen as relatively safe to pregnant women based on FDA labels; most of them are already on pharmacy shelves in developing countries, being used for diseases other than PE. Since they have not previously been tested for efficacy in PE, it is very likely that some may have beneficial effects.

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