Andrew Greenhill of Federation University Australia in Australia, along with partners at the Papua New Guinea Institute of Medical Research, will use advanced environmental microbiology methods to study microbial community dynamics associated with survival of the typhoid fever-causing bacterium Salmonella Typhi in aquatic environments in Papua New Guinea. "Typhoid Mary" Mallon was an Irish-American cook, written into infectious disease folklore as the first asymptomatic carrier of S. Typhi. More than eighty years after her death, little is still known about how the bacteria persists in environmental niches such as contaminated water, which is a major route of disease transmission. They will collect and filter water samples from streams in areas where the disease is common over an eight-month period covering both wet and dry seasons and analyze the microbial communities within by qPCR. This will be combined with physiochemical parameters of the water (temperature, stream height, photosynthetic activity) collected using DIMPP - a low-cost, late-stage prototype suitable for use in low-resource environments - to build network models. These models will be used to identify mathematical connections between environmental factors, aquatic populations, and the presence of antibiotic resistance genes. These connections could be used to develop an early warning system for impending outbreaks.

Matthew DeLisa of Cornell University in the U.S. will create a cell-free synthetic biology platform for low-income settings that produces thermostable polysaccharide-based conjugate vaccines against diarrheal pathogens upon the addition of water to a single tube. Half-a-million children under age five die each year from diarrhea and dysentery, the majority in low- and middle-income countries. Two major causes of bacterial diarrhea are enterotoxigenic E. coli (ETEC) and Shigella strains. Conjugate vaccines combine multiple antigens into one vaccine to increase its activity. However, they require a complex manufacturing process, living cells, and refrigerated storage, which limit their application in developing countries. They will develop the materials and methods for manufacturing thermostable anti-diarrheal vaccines in single tubes that only require the addition of water just ahead of administration. The tubes will contain a plasmid that can express an FDA-approved carrier protein, along with selected O-antigen-polysaccharides from ETEC or Shigella strains, and an enzyme that can conjugate the two via glycosylation, all within a freeze-dried pellet. Following development, they will test the safety, scalability and portability of the vaccines, and characterize their ability to generate effective antibodies that can kill the bacteria. The system is expected to reduce conjugate vaccine costs, and its modular nature will facilitate expansion to other vaccine-preventable diseases.

Hasan Uludag of RJH Biosciences in Canada will develop an affordable immunotherapy system based on genome-integrating transposons that works inside the body for the treatment of a wide variety of diseases such as cancer and diabetes. Emerging immunotherapies offer promising treatment for many diseases, but they require genetic modification of immune cells outside the body, and are thus labor intensive and expensive, limiting their utility in developing countries. They will use engineered nanoparticles in a new approach to immunotherapy that modifies immune cells inside the body. The nanoparticles are derived from polymeric materials that can encapsulate nucleic acids and proteins and release them into host cells. These nanoparticles will be dispersed in a hydrogel matrix with immunostimulatory molecules to create a living bioreactor inside the host that will attract and genetically modify immune cells. They will select polymers for their ability to deliver DNA-based transposons (to facilitate integration into the host genome) to immune cells and to stably express a reporter gene. Optimal polymers will be transferred into mice and they will evaluate transfection efficiency into immune cells with a fluorescent reporter gene. Finally, they will test the therapeutic efficacy of their in situ immune cell engineering approach in a mouse leukemia model.

Tovi Lehmann of the National Institute of Health in the U.S. will establish cross-country networks of aerial sampling stations in Africa to monitor windborne movement of insects and pests, and evaluate risks to public health, food safety, and ecosystem stability. Vector-borne disease is among Africa's top health priorities, and control of the insect vectors is the primary target for prevention. They will use a unique aerial sampling program to collect airborne insects across Mali and Ghana, and identify insects and pathogens within them by molecular analysis. Sticky nets mounted on helium balloons have shown, in a pilot project, to collect diverse samples, more representative of area fauna than ground sampling protocols. The same project showed that mosquitoes frequently travel (and may spread disease) over hundreds of kilometers. Overnight aerial sampling will be conducted ten nights per month for six months, followed by insect taxonomic identification and RNA/DNA sequencing to identify insects and pathogens. Weather data will be collected from the sampling stations at both ground level and sampling altitude and combined with population data for statistical analysis and simulation of flight patterns. They will produce dynamic, species-specific maps of select insects and pathogens with putative sites of origin, routes and destinations, which will be used to evaluate risks to public health and food security.