The University of Washington has launched its newest biomedical research enterprise, the center for Systems and Translational Research on Infectious Disease. The center is applying the latest in systems analysis and computational biology to find clinically useful defenses against difficult infectious diseases.
STRIDE is under the direction of Dr. Michael G. Katze, UW Medicine professor of microbiology and associate director of the Washington National Primate Research Center. The co-director is Dr. Timothy Rose, UW Medicine professor of pediatrics and a scientist at Seattle Children’s Research Institute.
“Some of my specific hopes for STRIDE include the design of novel antimicrobial drugs and the discovery of new ways to boost a patient’s own cellular immunity against a variety of pathogens. I also hope we will gain a better understanding of how viruses cause diseases as well as how the host contributes to the disease process, and what makes a good vaccine,” said Katze. “At present there are very few antiviral drugs. And there is no HIV vaccine nearly 30 years after the virus was identified. This tragic failure is what motivates me every morning.”
Describing the center’s enterprise as “rather huge,” Katze noted that the program brings together more than 40 scientists in many areas of infectious disease research, including AIDS, influenza, SARS, biodefense, and vaccine effectiveness. Research activities are currently funded by awards to STRIDE investigators, as well as education and training support from an American Recovery and Reinvestment Act award from the National Institutes of Health.
The organizational structure of STRIDE includes components for technology and animal models, infectious disease research, and translational research. Among the initial group of STRIDE investigators and their areas of research are: David M. Anderson, animal models, UW Comparative Medicine; Steven Self, biostatistics, Fred Hutchinson Cancer Research Center; Richard Smith, proteomics and metabolomics, UW Pathology; Ralph Baric, SARS and calciviridae infections in domestic animals, University of North Carolina Gillings School of Global Public Health; Michael Gale, Jr., innate immunology, UW Immunology; Yoshihiro Kawaoka, influenza, University of Wisconsin-Madison School of Veterinary Medicine; Tim Rose, AIDS-related malignancies, UW Pediatrics; Katze, virus-host interactions, UW Microbiology; Shawn Iadonato, clinical applications, Kineta, Inc., and Lynn Rose, clinical applications; UW Institute for Translational Health Sciences and Seattle Children’s.
The center takes systems biology approaches to study interactions between pathogens and their hosts. Pathogens are the germs that cause infectious disease. They can be viruses as well as harmful bacteria, parasites, yeasts, or fungi. A host is the plant, animal or person that the pathogen exploits to live and reproduce. The infection from these pathogens sets off a complex struggle that engages many cellular and molecular networks. Understanding this intricate system — its components, control mechanisms, signals, products, functions, timing, and failures — could lead to more effective ways to prevent and treat communicable diseases like AIDS, hepatitis C, SARS, pandemic flu, herpes, TB, malaria and others.
“Systems biology goes beyond figuring out what a single substance does, to looking at what is going on in an entire set of activities in live cells and how and when changes occur. Host and pathogen interactions are ideally suited to this approach,” said Dr. Paulene Quigley, research manager for STRIDE.
Systems biology has been gaining momentum in cancer studies, but STRIDE is the only center dedicated to applying it to infectious disease research. “I believe there is room for both traditional, hypothesis-based research and for systems biology research on infectious diseases,” Katze said. STRIDE will be encouraging new generations of scientists to work in infectious disease research through its training programs and its involvement with BioQuest, a career-inspiring science education effort for high school students and teachers.
At a recent Conference on Retroviruses and Opportunistic Infections, Katze presented an example of one system biology approach utilized at the new center: Starting with an animal model of a virus infection, researches use rapid, high-throughput technology to amass vast amounts of data from samples taken at many time points and under different conditions. This data includes information about genes and their products or regulatory roles (genomics), proteins and their function and interplay (proteomics) and energy storage and use (metabolomics) — and how the virus interferes with these activities.
Computational biologists then process this voluminous data to evaluate the hosts’ responses to the virus infection, Katze explained. Analyzing and integrating the data enables the scientists to create a computer model of these complex interactions, including key genes or biochemical pathways that could provide insight on ways the virus — or its mutants — perturbs the host. These scientific findings may suggest interventions that could be tested in models and be translated into novel medical therapies for clinical trials.
The center also will work closely with the UW Institute of Translational Research to rapidly turn promising scientific discoveries into safe, effective preventions and treatments for infectious diseases, including those common in developing nations. The STRIDE center, Quigley said, is in line with all five areas that Francis Collins, director of the National Institutes of Health, says are ripe for major advances that could reap substantial benefits. These include using high throughput technologies to broadly expand the scope of biological investigations, maximizing the speed of realizing the diagnostic and therapeutic implications of scientific breakthroughs, focusing on global health, improving the quality of health care, and reinvigorating the biomedical community through the training of new scientists.
“We see the new center as a place to bridge science and clinical care to reduce the burdens of infectious illnesses that afflict millions of people around the world,” Katze said.
In addition to his leadership of the new STRIDE center, Katze is director of the Center for Functional Genomics and Hepatitis C Virus (HCV)-Associated Liver Disease, co-director of the Pacific Northwest Regional Center of Excellence, principal investigator of a National Institute of Allergy and Infectious Diseases grant on the use of systems biology approaches to study emerging respiratory virus infections, and co-investigator of a Washington State Life Sciences Discovery Grant to use proteomics to identify markers of liver fibrosis. He also heads the Division of Functional Genomics and Infectious Disease at the Washington National Primate Research Center.