? This project will develop a realistic microsimulation of the pathogenesis of B. anthracis infection and the immune response mounted against it. This computational model is intended to complement the ongoing in vitro and animal studies and provide a means to integrate the information obtained in these various experiments. ? ? The investigators will study the transient functional reorganization of the immune system in response to B. anthracis infection. Anthrax lethal toxin appears to act largely by cleaving proteins in the signaling cascade that controls the synthesis of pro-inflammatory cytokines including TNF and IL-1 [beta]. This interference results in the overproduction of these cytokines, which are a key component of the host antibacterial response, but also mediate shock and cytotoxicity. It is not simply the overproduction of pro-inflammatory cytokines per se that drives the pathogenesis of anthrax, but the dysregulation of the normal transient reorganization of the immune system of which TNF and IL-1[beta] are a key part. ? ? The microsimulation will be constructed as a modular and multi-scale realistic computational model providing the means to explore this hypothesis, design experimental tests for its falsification and examine its implications for the design of novel therapies. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI058227-01A1
Application #
6821849
Study Section
Special Emphasis Panel (ZRG1-MABS (01))
Program Officer
Sawyer, Richard T
Project Start
2004-06-15
Project End
2006-05-30
Budget Start
2004-06-15
Budget End
2005-05-31
Support Year
1
Fiscal Year
2004
Total Cost
$192,500
Indirect Cost
Name
Duke University
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Chan, Cliburn; Kepler, Thomas B (2007) Computational immunology--from bench to virtual reality. Ann Acad Med Singapore 36:123-7
Kepler, Thomas B; Chan, Cliburn (2007) Spatiotemporal programming of a simple inflammatory process. Immunol Rev 216:153-63