Center for Modeling Immunity to Enteric Pathogens

The Center for Modeling Immunity to Enteric Pathogens (MIEP) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded program with an initial budget of $10.6 million directed by Dr. Bassaganya-Riera (Principal Investigator and Director of the Nutritional Immunology and Molecular Medicine Laboratory) with the mission of understanding the mechanisms of action underlying immune responses to enteric pathogens. MIEP is based at the Virginia Bioinformatics Institute (VBI) at Virginia Tech. Key partners in this project include the Center for Global Health at the University of Virginia and. The MIEP is part of the Modeling Immunity for Biodefense Program at National Institute of Allergy and Infectious Diseases along with the Program for Research on Immune Modeling and Experimentation (PRIME Center) at Mount Sinai School of Medicine, the Center for Computational Immunology at Duke University and the Center for Biodefense Immune Modeling at University of Rochester.
Team
The MIEP team includes over 30 researchers at NIMML and NDSSL with expertise ranging from immunology, computer science, mathematics, infectious disease, molecular biology, microbiology to high performance computing and it engaging the infectious disease and immunology communities to disseminate user-friendly mathematical and computational models for the study of human immunity to infection or vaccination. 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).
Working Areas
MIEP is organized in four major areas: computational/mathematical model development; immunological experimentation; bioinformatics; and education/outreach. The 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 (EAEC) and Helicobacter pylori. However, the models will be constructed so that simulation of immune responses to other NIAID category A-C priority enteric pathogens* (e.g., Salmonella, Shigella, and other types of E. coli pathogens) is also possible. A better understanding of the mechanisms of action underlying immune responses to emerging and re-emerging gut pathogens will lead to the development of broad-spectrum vaccines and immunotherapeutics.
Tools
The MIEP features two modeling tools: Complex Pathway Simulator (COPASI) and Enteric Immunity Simulator (ENISI) for ordinary differential equation and agent-based modeling, respectively. In addition, the MIEP website has made immune regulatory networks available in CellPublisher, a dynamic web interface that enables viewing of inter- and intracellular interactions at various levels of complexity via Google map APIs. The MIEP also develops new ways of enhancing interfaces between data and analyses/visualization tools.
COPASI is freely available and two versions are provided: one with easy to use graphical user interface that allows editing the model, running calculations, and viewing the results, and another version is a command line tool that can be used for batch processing or for interfacing with other software tools.
ENISI is a modeling environment for the inflammatory and regulatory immune pathways initiated by microbe-immune cell interactions in the gut. ENISI models are highly resolved in that individual cells are modeled along with their movement through different tissues, and probabilistic outcomes of cell-cell interaction are represented. It is scalable up to 10 million individual cells on a modest parallel cluster in 2 hours.

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