Awards

Pietro Alano of the Instituto Superiore de Sanità in Italy will develop a biochip that mimics the midgut of the Anopheles mosquito and can be used to more easily and quickly test candidate anti-malarial compounds for blocking transmission of the causative Plasmodium parasite. Malaria is a potentially fatal infection caused by parasites transmitted between humans through the bites of infected mosquitoes. When a mosquito bites an infected person, immature Plasmodium gametocytes enter the mosquito and transform into an invasive ookinete stage in its midgut. They then traverse the gut wall to the external gut lumen, where they enter their parasite stage. To eliminate malaria, compounds are needed that block the transmission of Plasmodium. However, current methods to evaluate the candidate transmission-blocking drugs or vaccines that are under development are slow and involve feeding malaria-infected blood to mosquitoes, which is potentially dangerous. As an alternative, they will create a biochip to reproduce the mosquito midgut environment that can support the development of parasites, and develop a bioluminescent antibody-based technique to count successfully traversing ookinetes. They will test the performance of the biochip using known anti-transmission drugs.

Fredros Okumu of the Ifakara Health Institute in Tanzania will develop technology to evaluate mosquito control interventions using a combination of artificial intelligence, infrared spectroscopy, and entomology. Malaria caused over 400,000 deaths in 2017, the majority in the developing world, and an effective way to control the disease is to target the mosquitoes that transmit it. Current tools cannot precisely measure mosquito age or life-expectancy, and are therefore unable to predict the impact of mosquito control interventions. The biochemical composition of the mosquito exoskeleton varies with species and age; as the types of chemical bonds change so does the amount of light absorbed in the mid-infrared region. This can be measured with mid-infrared spectroscopy (MIRS), and they will combine this with machine learning to measure the age of mosquito populations. Using a dataset collected from over 25,000 lab-raised mosquitoes, they have developed a supervised machine learning model that accurately predicts mosquito age and species. They will optimize this model to work also on wild mosquito populations, develop an online platform for real-time analysis of mosquito MIRS data, and test its ability to measure the effectiveness of malaria control interventions.

Marnie Winter and Benjamin Thierry from the University of South Australia, together with Tina Bianco-Miotto, Claire Roberts, and Clare Whitehead of the University of Adelaide in Australia and the University of Toronto in Canada, will develop and test short-interfering RNAs (siRNA) high-density lipoprotein (HDL) nanocarriers for the treatment of preeclampsia. Globally, ten million women develop preeclampsia during pregnancy each year, which results in the deaths of 76,000 women and 500,000 babies; 99% of these are in developing countries. Most current treatments focus on treating the symptoms (high blood pressure and proteinuria) rather than the molecular causes. Some of the causative molecules, such as the angiogenesis inhibitor sFlt1, can be blocked by specific siRNAs, but the challenge is targeting the siRNAs to the right cells in the body. HDL delivery systems for this purpose are effective and safe, and both siRNAs and HDLs are stable at room temperature, important for therapies in resource-poor areas. They will optimize the formulation of their HDL nanocarrier manufacturing platform, and characterize siRNA loading, carrier stability, size, cellular uptake, and silencing ability in 2D culture. Further, they will bioengineer an ex-vivo placenta model that fully recapitulates the structural and phenotypic complexity of a preeclamptic placenta and use it to evaluate tissue penetration and silencing abilities of the siRNA-nanocarrier complex.

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.

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.