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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. Unless otherwise noted, all seminars are held on Wednesdays in the Molecular Science and Engineering Building ("M" Building) in G011 (Cherry Logan Emerson Lecture Theater) at 4 p.m. Refreshments are served at 3:30 p.m. in the Emerson-Lewis Reception Salon. NOTE: The location for this seminar is the Pettit Microelectronics Building, Room 102 A-B.
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“Advances in Systems Immunology: Characterizing the Host Response Induced by Influenza Virus Infection”
Jason Shoemaker, Research Assistant Professor, Department of Microbiology and Immunology, University of Tokyo
Abstract:
Highly pathogenic influenza virus infections invoke distinct inflammatory response dynamics, yet the factors driving these distinctions remain unknown. There has been a growing trend in virus research to identify the proteins and genes responsible for the distinct dynamics and attempt to exploit these factors for therapeutic gain, but the approaches often ignore the complex, nonlinear interactions that may exist between virus growth, the immune response, and disease pathology. Our lab focuses on developing analytical tools for elucidating and modeling the complex regulatory architecture of the immune response. We especially emphasize the importance of developing approaches to infer models from tissue-level, whole-genome data. In this presentation, I will introduce systems inference microarray analysis (SIMA) for developing nonlinear, species-specific models, and CTen, a web-based analytical platform for associating sets of genes with specific immune cells. These tools were applied to microarray data developed from the lungs of influenza-infected mice to determine the factors that regulate immune response dynamics. Our analysis found that the dynamics of a key inflammatory event – the cytokine storm – is regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal inflammatory gene expression but expression is strongly induced once a threshold virus titer is exceeded. A mathematical model of the ultrasensitive response performed well for all strains and inoculation conditions tested; suggesting that virus-intrinsic properties (e.g. differences in interferon antagonism) are not strong determinants of the cytokine storm and that a novel means of protecting high risk groups could involve manipulating the molecular mechanisms responsible for the threshold behavior. We then show that changes in the cell count of many inflammatory leukocytes (e.g. macrophages, NK cells, T cells and B cells) can be determined from tissue-level gene expression data. This is a key first step to developing data-driven models that link immune cell activity and intracellular signaling to disease pathology. Such models may provide critical insight into the treatment of several diseases including microbial infections and severe allergic responses.
