Therapeutics/Drugs

Jay Keasling of Zagaya in the U.S. will explore the production by an endophytic fungus of artemisinin, a key ingredient in malaria treatments. If the fungus produces artemisinin in the absence of light, an enzymatic mechanism is likely involved. This mechanism could be harnessed for a new production method to reduce treatment costs for malaria patients in developing countries.

Erdogan Gulari of the University of Michigan in the U.S proposes to design and produce a large library of antimicrobial peptides (AMPS) that will be tested against Mycobacterium tuberculosis strains to identify potential new drugs that can damage the bacterial membrane and be less susceptible to evasion by the development of resistance.

Feng Zhang of the Broad Institute of MIT and Harvard in the U.S. proposes to engineer bacterial viruses to deliver enzymes that can be designed to degrade the genome of pathogenic bacteria. These bacteriophages could be used as a new platform for treating drug-resistant bacterial infections.

Mark van Raaij of the Spanish National Research Council (CSIC) at the National Center for Biotechnology in Spain will work to build a library of engineered bacteriophages that can recognize, infect, and kill a range of enterobacteria such as Salmonella and E. coli.

Linda Broadbelt and Keith Tyo of Northwestern University in the U.S. propose to use a computer-aided design (CAD) tool to identify new metabolic mechanisms of action in priority drugs for the developing world. Understanding of these pathways could help optimize methods to produce low-cost versions of these therapeutics in microbes.

Thumbi Mwangi of Washington State University in the U.S. will work at the Kenya Medical Research Institute in Kenya to test whether treatment of parasitic helminth infections reduces the severity of the co-occurring parasitic diseases malaria and East Coast Fever (ECF) in humans and cattle respectively, which are more difficult to treat. In many developing countries, humans carry more than one parasitic disease, but if and how they interact to affect disease impact, for example by modifying the immune response, is not well understood.

Agenor Mafra-Neto of ISCA Technologies, Inc. in the U.S. will test whether an artificial lactic acid treatment (called abate) can trick disease-transmitting insects such as mosquitoes into infecting animals rather than their preferred human hosts, thereby reducing infection rates. Malaria-causing parasites are carried by mosquitoes, which identify the human hosts that help them reproduce by detecting the high levels of lactic acid in human perspiration.

Honorine Ward of Tufts Medical Center with Mary Estes at Baylor College of Medicine in the U.S. and Gagandeep Kang at Christian Medical College in India will develop a three dimensional cell culture model (enteroid) of the human intestine to study environmental enteric dysfunction (EED), which is associated with substantial morbidity in young children in the developing world. They will grow enteroids from isolated intestinal crypts derived from unused surgical samples from children with and without EED in India.

Cirle Warren from the University of Virginia in the U.S. will develop a mouse model with an intestinal tract that is primed to mimic the human intestine in order to better study enteric infections and identify effective treatments. Several environmental enteropathies cannot be studied in the mouse because they do not simulate the human physiological response. To address this, they will test different conditions for transplanting feces from healthy children into pregnant mice to transfer human gut microbes and promote the development of a 'humanized' gut in the unborn mice.

Linda Saif from Ohio State University in the U.S. will develop a pig model to recapitulate the vicious cycle of malnutrition and repeated enteric infections seen in young children in developing countries in order to study the underlying biology and identify effective treatments. Childhood malnutrition is rife in impoverished regions, and causes substantial mortality and disabilities. It impairs gut function and immunity, and leads to increased enteric infection rates.