Infectious Disease

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.

Mark Davis of Stanford University in the U.S. will develop a new method to assess specific T cell responses to vaccinations. Using combinations of labeled tetramers to identify many types of T cell responses, Davis hopes to create better and more comprehensive assessments of immunity generated by vaccines. This project's Phase I led to the development of a new way to color-code T cells as a way to visually quantify immune response to an influenza vaccine.

Optical information, temperature gradients, trace gases and volatile odors are key sensory inputs for mosquitoes. To mitigate the transmission of malaria, Szabolcs Marka of Columbia University in the U.S. will research how optical irradiation might be used to physically disrupt mosquitoes' sensory systems such that they can't find human hosts. This project’s Phase I research demonstrated that insects are repelled or change their flight behavior in response to different infrared light gradients.

Keith Jerome of the University of Washington in the U.S. will utilize a class of proteins called homing endonucleases, which have the ability to cut DNA sequences, to target the DNA sequences unique to HIV, thus disabling the virus from making any more copies of itself. This project’s Phase I research demonstrated that homing endonucleases can find a model virus hidden in the genes of infected cells. In Phase II, Jerome’s team is now modifying these proteins in hopes of producing several that can specifically target and destroy HIV within infected cells.

Dan Feldheim of the University of Colorado in the U.S. will test his hypothesis that gold nanocrystals coated with drug compounds can effectively inhibit protein-protein interactions that often drive disease pathogenesis, will be less susceptible to evolutionary mechanisms that lead to drug resistance, and offer enhanced drug delivery characteristics. This project’s Phase I research demonstrated that gold nanocrystals can be tailored to circumvent many viral and bacterial evolutionary drug resistance mechanisms.

To fight emergence of drug and vaccine resistance in rapidly evolving parasites, Pradipsinh K. Rathod of the University of Washington in the U.S. will identify the parts of the malaria genome which contribute to rapid increases in mutations, and will screen for small molecules that inhibit these mechanisms. This project’s Phase I research demonstrated that hypermutagenesis does play a strong role in the development of drug resistance.

Xilin Zhao of the University of Medicine and Dentistry of New Jersey will test whether anaerobic gas, which causes rapid depletion of oxygen, will kill the tuberculosis bacteria without permanent damage to surrounding tissue.

Dirk Linke of the Max Planck Society in Germany seeks to identify and classify all the molecules that make up the cell wall of gram-negative bacteria, which causes a major portion of infectious diseases. By recognizing common elements among these molecules, a broad-range vaccine could be developed to protect against a number of these diseases.

In the developing world, many people with health problems never receive an accurate diagnosis or appropriate treatment because clinicians lack tools to detect and diagnose diseases and conditions quickly, accurately, and inexpensively. Sophisticated medical tests that could help improve care are not only often unaffordable, they require extensive laboratory facilities and deliver results days later - a hardship for people who may live many miles from the nearest health clinic. Dr.

In the developing world, lack of convenient and accurate tools that can detect and diagnose diseases and other health problems means that many health risks remain undetected or receive inappropriate treatment. Dr. Yager's team, in collaboration with research groups from private industry as well as the nonprofit sector, is working to develop a low-cost, easy-to-use device that will rapidly test blood for a range of health problems prevalent in developing countries, such as bacterial infections, nutritional status, and HIV-related illnesses.