The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has awarded a $10.6 million grant to researchers at the Virginia Bioinformatics Institute (VBI) and collaborators to determine how the human immune system responds to infection by pathogens of the gut. The funding will be used to apply mathematical modeling to the study of immune responses to gut pathogens.
"The Center for Modeling Immunity to Enteric Pathogens will generate new hypotheses based on computer simulations of the immune responses in the gut and perform pre-clinical and clinical experiments that will reveal how the immune system works when intestinal pathogens invade the human body," said Josep Bassaganya-Riera, principal investigator of the center, associate professor at VBI, and leader of the Nutritional Immunology and Molecular Medicine Group in VBI's CyberInfrastructure Division.
"We want to use powerful computer simulations to uncover the mechanisms of action underlying immune responses to intestinal pathogens and accelerate the discovery of drug targets suitable for the prevention and treatment of diseases and disorders caused by gut pathogens, such as persistent diarrhea, gastric cancer, inflammation, and ulcers," said Bassaganya-Riera.
The research project team will work with a wide range of collaborators and engage the infectious disease and immunology communities to disseminate user-friendly mathematical and computational models for the study of human immunity to infection or vaccination.
"Food- and water-borne illnesses that arise from infections with gastrointestinal pathogens cause an enormous health burden around the globe," said Richard Guerrant, director for the Center of Global Health in the Division of Infectious Diseases and International Health at the University of Virginia School of Medicine. "Escalating medical costs, lost productivity, and premature death are linked to annual outbreaks of pathogens that target the intestinal tract of humans. This project sets out to address the need for more informed scientific research that translates into effective clinical solutions for gastrointestinal infections. It should open novel approaches to providing much needed health solutions to individuals in both developing and industrialized countries."
The Center for Modeling Immunity to Enteric Pathogens is organized into four major areas: computational/mathematical model development, immunological experimentation, bioinformatics, and education.
"Generations of life scientists have worked in a reductionist paradigm to provide crucial insight into the interactions between biological systems at scales ranging from organs, tissues, and cells to molecules," said Stephen Eubank, deputy director of the Network Dynamics and Simulation Science Laboratory at VBI. "What's been lacking is a holistic understanding of how all these pieces function together in a real organism with all its messy irregularity, heterogeneity, and complexity across scales."
Added Madhav Marathe, deputy director of the Network Dynamics and Simulation Science Laboratory at VBI: "Extremely detailed interaction-based modeling is a natural approach to understand these systems. This can only be achieved through high-performance computational modeling and simulation that will stretch the capabilities of even the most powerful machines -- a beautiful example of a petascale computing problem. This project is a first step in that direction, with a focused application on enteritis and well-integrated computational and laboratory research teams. An important goal is to allow biologists to use these sophisticated tools without becoming computing experts."
Bruno Sobral, director of the CyberInfrastructure Division at VBI, said: "I am delighted to see this project emerge both for the specific biology and infectious disease community that it will serve, but also because of its great strategic cohesion with all of the activities in the CyberInfrastructure Division. It ties with other crucial projects that we are engaged in, such as the Middle Atlantic Regional Center of Excellence for Biodefense and Emerging Infectious Diseases and VBI's PathoSystems Resource Integration Center (PATRIC). It is because of the integrated biology of host-pathogen-environment interactions that underpins infectious diseases in the real world that these projects also are coordinated through key leaders such as Dr. Bassaganya-Riera. The opportunities within and across projects are substantial, with benefits to all."
A better understanding of the mechanisms of action underlying immune responses to emerging and re-emerging gut pathogens promises to lead to the development of broad-spectrum vaccines and immunotherapeutics.
Learn more about the Center for Modeling Immunity to Enteric Pathogens
In addition to providing a user-friendly web-based immunological information system that incorporates the models, the Center for Modeling Immunity to Enteric Pathogens (MIEP) is programmatically tied to the Immunology Database and Analysis Portal (ImmPort) and the Middle Atlantic Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (MARCE), and offers training on modeling mucosal immune responses to biodefense-related National Institute of Allergy and Infectious Diseases (NIAID) category A-C priority enteric pathogens.
MIEP will assist researchers in their efforts to develop new vaccines and host-targeted broad-based therapeutics for biodefense. Understanding immunity to gastroenteric pathogens is an important step in biodefense, especially as it relates to food-borne illness. As a proof-of-concept, researchers will focus initial efforts primarily on modeling immunity to enteroaggregative Escherichia coli and Helicobacter pylori. However, the models will be constructed so that simulation of immune responses to other NIAID category A-C priority enteric pathogens, such as Salmonella, Shigella, and other types of E. coli pathogens, is also possible. (A full list of the selected NIAID category A-C priority pathogens is available at:
About the Nutritional Immunology and Molecular Medicine Group
The Nutritional Immunology and Molecular Medicine Group at VBI's CyberInfrastructure Division conducts translational research aimed at developing novel therapeutic and prophylactic approaches for modulating immune and inflammatory responses. The group combines computational modeling, bioinformatics approaches, animal experimentation and human clinical studies to better understand the mechanisms of immune regulation at mucosal surfaces and ultimately accelerate the development of novel treatments for infectious and immune-mediated diseases. www.vbi.vt.edu/nimm
About the CyberInfrastructure Division
The CyberInfrastructure (CI) Division at VBI develops methods, infrastructure, and resources to help enable scientific discoveries in infectious disease research and other research fields. The division applies the principles of cyberinfrastructure to integrate data, computational infrastructure, and people. CI has developed many public resources for curated, diverse molecular and literature data from various infectious disease systems, and implemented the processes, systems, and databases required to support them. It also conducts research by applying its methods and data to make new discoveries of its own.
About the Virginia Bioinformatics Institute
The Virginia Bioinformatics Institute (http://www.