The Bill & Melinda Gates Foundation has awarded its latest set of grants supporting innovative scientific research aimed at solving problems in global health.
The grants, awarded through the Gates Foundation’s $100 million Grand Challenges Exploration program, for this go-round appear to favor novel methods aimed at combating malaria.
Like using microwaves to treat malaria infection. Or using the smell of your feet to mislead mosquitoes.
“Finding solutions to persistent global health problems is a difficult, lengthy and expensive process,” said Chris Wilson, director of Global Health Discovery at the Bill & Melinda Gates Foundation. This program, Wilson said, “was designed to tap the innovators of the world by providing resources needed to explore bold ideas that are typically too risky to attract funding through other mechanisms.”
Here’s the press release issued by the Gates Foundation and a story by Donna Blankinship of the Associated Press in Seattle. First-time grant winners get $100,000 to pursue their ideas and if they show promise are eligible to receive up to $1 million for “Phase II” studies.
Three projects, including the one exploring the use (in mice only right now) of microwave irradiation to kill malaria parasites, received Phase II funding, the philanthropy reported. Blankinship asked Wilson about the idea of using microwaves as a malaria treatment. The purpose of Grand Challenges, he emphasized, is to support high-risk — some might even say wacky — ideas.
“That’s probably not going to work,” Wilson said. “But if it did work, it would be pretty stunning.”
Here’s the full list of this round of funded projects with brief descriptions:
Use of Microwave Frequency as Treatment for Malaria
Carmenza Spadafora of Panama’s Institute of Advanced Scientific Investigations and High Technology Services and José A. Stoute of Pennsylvania State University College of Medicine investigated whether malaria can be treated by microwave irradiation, an idea based on the unique electromagnetic properties of hemozoin, a metabolite formed by Plasmodium parasites in infected red blood cells. This project’s Phase I research demonstrated that malaria parasites inside red blood cells are sensitive to low doses of microwaves that do not harm uninfected red blood cells. The Phase II grant (awarded to Dr. Stoute) will allow them to extend their results from the Phase I grant (awarded to Dr. Spadafora) by validating parasite killing effects in a mouse model of malaria and exploring the mechanism by which microwaves induce parasite death.
Drugs That Target Multiple Receptors for Antihelmintics
Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project’s Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.
Reducing the Burden of Malaria by Targeting Hotspots of Malaria Transmission (REDHOT)
Teun Bousema of Radboud University in the Netherlands proposed that geographic “hotspots” of malaria disease drive local transmission, and therefore that interventions would most efficiently be deployed if they targeted these hotspots. This project’s Phase I research demonstrated that hotspots of malaria transmission are present at all levels of endemicity and can be sensitively detected by serological markers of malaria exposure. In Phase II, Bousema and colleagues will define hotspots of malaria transmission in Africa in a site of moderate endemicity in Mali and in the low endemicity highlands in Kenya. Once hotspots are detected, they will be targeted with a combination of those interventions deemed most efficacious based on a mathematical simulation, the goal being to locally interrupt malaria transmission.
Pathogen Sense and Destroy
Saurabh Gupta and Ron Weiss of Massachusetts Institute of Technology proposed creating sentinel cells that can detect the presence of a pathogen, report its identity with a biological signal, and secrete molecules to destroy it. This project’s Phase I research demonstrated that commensal bacteria can be engineered to detect and specifically kill the model bacterial pathogen Pseudomonas aeruginosa. In Phase II, Gupta and Weiss will engineer the human microbiota to specifically detect and destroy the gut pathogen Shigella flexneri, which is responsible for high mortality rates in children.
Protein Glycan Coupling Technology and the Development of Novel Conjugate Vaccines
Brendan Wren of the London School of Hygiene & Tropical Medicine in the UK will test a new bacterial synthesis method, Protein Glycan Coupling Technology. This method uses bacteria to attach proteins to glycans to produce glycoconjugate vaccines, and it could lead to an improved vaccine against pneumococcal disease. This project’s Phase I research demonstrated that a Streptococcus pneumoniae capsular polysaccharide could be transferred to a carrier protein in E. coli. In Phase II, this research will be extended to further capsular determinants with the goal of producing a broad coverage, inexpensive pneumococcal vaccine.
Autophagy as a Cell-Autonomous Defense to Eliminate HIV
Vojo Deretic of the University of New Mexico proposed that authophagy, a process by which cells destroy cellular components and intracellular pathogens, can be induced through drug therapy to not only destroy the HIV virus in infected cells, but also to block its transmission from dendritic cells to T cells. The projects’ Phase I research demonstrated that autophagy can destroy HIV, block dendritic to T cell transfer of HIV, and promote antigen presentation by dendritic cells. In Phase II, Deretic’s team will screen for compounds that can induce autophagy to block HIV from infecting cells, limit HIV spread, and enhance dendritic cell immune functions.
Design of an Effective Vaccine against HIV: An Alternative Hypothesis
Because a robust immune response can actually foster HIV replication and spread, Joseph (Mike) McCune at the University of California at San Francisco proposed that building tolerance to HIV will hinder disease progression better than vaccinations that activate the immune system and trigger HIV activity. This project’s Phase I research demonstrated in a non-human primate model that tolerance to SIV could be induced by introducing SIV antigens to fetuses in utero. In Phase II, McCune and colleagues will work to optimize this approach by identifying which antigens best confer this “protective immunity,” and testing whether and how long this protection lasts after birth.
Mucosal Delivery and Retention of Anti-HIV Agents Using Lactobacillus
Shi-hua Xiang of the Dana Farber Cancer Institute proposed engineering Lactobacillus, bacteria which normally reside in the human genital and gastrointestinal tract, to carry anti-HIV agents such as neutralizing antibodies, peptides, or other inhibitors. He and his colleagues hypothesized that introducing the engineered bacteria into the gastrointestinal tract would allow the bacteria to colonize and provide long-lasting protection against the virus. This project’s Phase I research demonstrated that the engineered anti-HIV Lactobacillus can efficiently block HIV infection in a tissue culture system. In Phase II, Xiang (now at the University of Nebraska) and colleagues are testing this approach in a non-human primate model.
Using Outdoor Infrastructure for Malaria Eradication
Existing malaria vector control methods (e.g. nets and insecticide sprays) primarily target mosquitoes that enter or attempt to enter human dwellings, yet mosquitoes also obtain significant proportions of essential resources outdoors. Fredros Okumu of Ifakara Health Institute in Tanzania and his co-investigators therefore proposed the use of strategically-located outdoor vector control devices. In this project’s Phase I research, the team created new and easy-to-use outdoor methods for luring, trapping and killing mosquitoes, including major African malaria vectors. By combining mosquito lures with mosquito-killing agents, they showed that in addition to trapping, it was consistently possible to contaminate and slowly kill between 74% and 95% of wild malaria vectors visiting the outdoor devices. In Phase II, the team will improve their decoy prototypes and explore practical ways in which the outdoor mosquito control strategy can be implemented by rural and remote communities in malaria endemic areas.
New Screening Technologies for Drug Discovery of Latent Malaria Infections
Ronald Quinn of Griffith University’s Eskitis Institute in Australia and colleagues are seeking to discover chemical fragments drawn from a variety of natural sources that bind to proteins expressed by the malaria parasite in its latent stage and the tuberculosis microorganism. In their Phase I and Phase II research, the team is working on identifying compounds that target proteins involved in key metabolic and energy pathways of latency as the basis for new drug therapies.
Magneto-Optical Biosensors for Malaria Diagnosis
Luke Savage and Dave Newman led engineers at Exeter University in the UK in a program to develop a handheld, inexpensive battery-powered instrument that can rapidly diagnose malaria. By using magneto-optics to detect the hemozoin crystals produced as a byproduct of malaria parasite digestion of hemoglobin in the red blood cell, they avoid relying on invasive blood sampling. The project’s Phase I research produced a robust hand-held diagnostic device able under laboratory conditions to detect malarial infection at well below 100 parasitized red blood cells per microliter in less than two minutes. In Phase II, simpler yet improved second generation devices will undergo further development and clinical testing under field conditions until they can meet the sensitivity and specificity standards required of a test for malaria.
Oral drug treatment for enhanced immune control over HIV replication
Dennis Hartigan-O’Connor of the University of California at San Francisco proposed testing whether expanding Th17 cell populations, a subset of CD4 T cells that protect the gastrointestinal tract against microbes, can augment the gut’s general defenses and protect against the acute and chronic effects of HIV. In this project’s Phase I research, Hartigan-O’Connor and colleagues tested this hypothesis in macaques and found that the Th17 population present before SIV infection has a lasting impact on the course of disease and that natural variability in Th17 populations might partly account for variability in control of SIV infection. In Phase II, the team will test the idea that an oral drug can be used to pharmacologically manipulate Th17 populations in vivo in young macaques, the goal being enhanced control of retroviral replication.
