Knowledge Generation

Xinquan Wang of Tsinghua University in China will study the molecular mechanism of MERS-CoV neutralizing antibodies (MERS-4 and MERS-27) and further increase their potency by combining structural, biochemical, and virological methods.

Xue Liu of Tsinghua University in China will identify antibacterial small molecules against the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) by screening compound libraries that contain compounds with novel chemical scaffolds. They will then use the identified antibacterials as probes to find new targets for antibiotic development. The current data include the discovery of two bacteriocidal compounds with novel scaffold structures.

Ye Xiang of Tsinghua University in China will study enveloped virus glycoprotein structures as a means to better understand the mechanisms by which enveloped viruses infect their hosts. The results obtained will contribute to the general knowledge of enveloped virus infection and maturation in addition to providing important information for vaccine and viral drug design for enveloped viruses such as HIV.

Bryan Hsu from Harvard Medical School in the U.S. will develop a mouse model carrying specific bacteria to mimic conditions in the infant gut for studying bacteria-infecting viruses known as phage, which could be valuable agents for treating infectious diseases and promoting child health in developing countries. Understanding how phage behave within the complex human gut is a critical step towards developing phage-based therapeutics that can safely modify resident bacterial populations.

William Hanage from the Harvard T. H. Chan School of Public Health in the U.S. will develop an approach to better monitor the evolution and spread of microbial resistance to antibiotics, which is a major public health concern. Current approaches are generally slow, not widely available, and limited to analysis of a single pathogen, while often multiple pathogens coexist in each sample. They will trial a method they have developed to identify DNA sequences (motifs) linked with resistance to pneumococcus and gonococcus from existing genomic data.

Jennifer Mahony and Douwe van Sinderen of University College Cork in Ireland, with Marco Ventura of University of Parma in Italy, will study how bacteriophage, which are viruses that infect and kill bacteria, affect both beneficial and pathogenic bacterial populations over time in the guts of infants from developing countries, which ultimately influence infant health and well-being.

Francisco Diéguez from Disal in Chile will determine whether samples collected from portable toilets found across Pacific coastal regions in South America can be used to monitor pathogenic diseases and antibiotic resistance and help combat these major public health concerns. The portable toilets are tagged with electronic chips that are used to monitor their location and state. They will develop a method for weekly collection and storage of fecal and urine samples from toilets in and around Lima, Peru.

Warren Zipfel of Cornell University in the U.S. will develop a simple, low-cost method to quantify levels of the tuberculosis-causing bacteria Mycobacterium tuberculosis in different tissues by measuring fluorescence emitted by one of its proteins, F420. To decrease the cost they will use a pulsed laser diode for F420 excitation, and analog electronics to process the fluorescence signal. They will optimize the detection circuitry and optics components, and evaluate its sensitivity and capacity for quantifying the bacteria in sputum and lung tissue.

Paul Bollyky from Stanford Medical School in the U.S. will study whether filamentous phage – viruses that infect bacteria – direct structural changes in the lining of the intestines and thereby promote the growth of healthy bacteria to protect against disease. Phage are considered to be a potentially rich therapeutic resource for infectious diarrhea and environmental enteropathy, which are prevalent in developing countries, but much remains to be learned about them.

Timothy Julian of the Swiss Federal Institute of Aquatic Science and Technology (EAWAG) in Switzerland will develop a low-cost approach to monitor the development of resistance to antibiotics, which is a major public health concern. Identifying antibiotic resistance requires sequencing and with current protocols is costly. To address this, they will first enrich samples for 30 antibiotic resistance genes using oligo-coated magnetic beads to increase the efficiency of the sequencing and substantially reduce the cost per sample.