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Modeling the Biological Reponse to Influenza A Virus

The objectives of this project are to develop multiscale models of lung injury caused by either primary Influenza infection or secondary pneumonia, and identify from simulations optimal intervention strategies in non-trivial situations, such as highly virulent pathogens and sub-optimal immunization.

This effort will include the development of reduced and more detailed models of the host-influenza interaction, the innate and adaptive immune response and pulmonary gas exchange under evolving lung injury. These models will be calibrated with prospective data from a series of animal experiments, including non-human primate models,  with strains of Influenza of varying virulence, with or without immunization, and with or without antiviral pharmacotherapy.

Our group of interdisciplinary investigators have for several years been working to develop theoretical and animal models of infection and inflammation. When completed, these projects will have accomplished three important scientific goals:

(1) Provide a solid biological basis for assumptions used in the design of individual and population-based containment strategies of highly virulent Influenza.

(2) Provide a foundation for further studies of multiscale whole organ models including mechanisms of organ failure.

(3) Provide quantitative methods to assess the uncertainty associated with model predictions when such models are calibrated from imperfect or sparse empirical data.

These activities involve the training post-doctoral fellows, graduate and undergraduate students in an interdisciplinary environment strongly dedicated to scientific dissemination to clinicians, biologists and quantitative scientists. This project confirms the investigators strong continued commitment to the training of women scientists, and will reach out to underrepresented minorities, particularly at the undergraduate level.

This research is supported by National Institute of General Medical Sciences - 5R01GM083602-04



G. Bard Ermentrout

Elodie Ghedin

Roni Rosenfeld

Ted Ross

David Swigon