The overall goal of this Program Project Grant (P01) is to define the key interactions between multiple intracellular pathogens and infected host cells. Over the last 10 years, many of the host innate immune pathways involved in sensing microbial infection have been identified. The receptors controlling the activation of these pathways include the Toll-like receptors (TLRs) and a growing family of cytosolic receptors including Nods, Naips, Nalps, and multiple cytosolic nucleic acid sensors. Importantly, the contribution of each of these pathways during a microbial infection will differ based on the composition, lifestyle, and virulence mechanisms of that microbe. Core B of this P01 will maintain a colony of mouse strains with deficiencies in components of innate immunity or other genetic modifications useful for the study of innate immunity. Core B also supports an ENU-based forward genetic screen to identify new genes involved in host defense during L. monocytogenes, L. pneumophila, and M. tuberculosis infection. Mice and macrophages derived from these mice will be distributed to each of the projects within the P01. All mouse strains have been or will be backcrossed onto the C57B1/6 genetic background to equivalent degrees. Core B will reduce overall mouse costs due to economies of scale. In addition, each P01 project will benefit from using cells and mice with fewer genetic and experimental variations.

Public Health Relevance

Core B will provide mice and cells lacking key immune genes to each of the projects within this P01 application. Experiments using these materials will dissect how the immune system detects and responds to a broad range of pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI063302-11
Application #
8700309
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
11
Fiscal Year
2014
Total Cost
$342,238
Indirect Cost
$88,231
Name
University of California Berkeley
Department
Type
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Kranzusch, Philip J; Lee, Amy S Y; Wilson, Stephen C et al. (2014) Structure-guided reprogramming of human cGAS dinucleotide linkage specificity. Cell 158:1011-21
Burke, Thomas P; Loukitcheva, Anastasia; Zemansky, Jason et al. (2014) Listeria monocytogenes is resistant to lysozyme through the regulation, not the acquisition, of cell wall-modifying enzymes. J Bacteriol 196:3756-67
B├ęcavin, Christophe; Bouchier, Christiane; Lechat, Pierre et al. (2014) Comparison of widely used Listeria monocytogenes strains EGD, 10403S, and EGD-e highlights genomic variations underlying differences in pathogenicity. MBio 5:e00969-14
Tenthorey, Jeannette L; Kofoed, Eric M; Daugherty, Matthew D et al. (2014) Molecular basis for specific recognition of bacterial ligands by NAIP/NLRC4 inflammasomes. Mol Cell 54:17-29
Lee, Bettina L; Barton, Gregory M (2014) Trafficking of endosomal Toll-like receptors. Trends Cell Biol 24:360-9
Sivick, Kelsey E; Arpaia, Nicholas; Reiner, Gabrielle L et al. (2014) Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies. Cell Host Microbe 15:203-13
Archer, Kristina A; Durack, Juliana; Portnoy, Daniel A (2014) STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes. PLoS Pathog 10:e1003861
Arpaia, Nicholas; Barton, Gregory M (2013) The impact of Toll-like receptors on bacterial virulence strategies. Curr Opin Microbiol 16:17-22
Isaac, Dervla T; Coady, Alison; Van Prooyen, Nancy et al. (2013) The 3-hydroxy-methylglutaryl coenzyme A lyase HCL1 is required for macrophage colonization by human fungal pathogen Histoplasma capsulatum. Infect Immun 81:411-20
Aachoui, Youssef; Leaf, Irina A; Hagar, Jon A et al. (2013) Caspase-11 protects against bacteria that escape the vacuole. Science 339:975-8

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