DNA variations impact immune host response through the perturbations they cause to transcriptional and biological networks, providing a molecular phenotype* that is an intermediate to the clinical phenotype. By integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data, we are now able to infer transcriptional networks capable of representing causal relationships among genes and traits in the network. This provides the opportunity to identify multiple genetic perturbations that alter the states of molecular networks and that in turn move systems into disease states. Specifically, by dissecting immunogenetic traits, we are able to elucidate key drivers of immune host response beyond what could be achieved by traditional genetic association studies alone. The Systems Immunogenetics core (Core D) will provide critical statistical genetics and computational biology expertise to the U19 investigators across all projects by guiding experimental design with appropriate biostatistical oversight, providing state-of-the-art systems genetics analysis and modeling approaches and ensuring that the vast amounts of data generated are rapidly integrated to identify key genetic regulators of immune phenotype and response to SARS, Influenza and West Nile Viruses.

Public Health Relevance

The Systems Immunogenetics Core provides the blostatistical and computational modeling expertise to elucidate the genetic basis of host immune response and to use this knowledge to aid in prioritization and identification of targets for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI100625-01
Application #
8369982
Study Section
Special Emphasis Panel (ZAI1-QV-I (M3))
Project Start
Project End
Budget Start
2012-08-05
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$546,103
Indirect Cost
$84,234
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Maurizio, Paul L; Ferris, Martin T; Keele, Gregory R et al. (2018) Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice. G3 (Bethesda) 8:427-445
Green, Richard; Ireton, ReneƩ C; Gale Jr, Michael (2018) Interferon-stimulated genes: new platforms and computational approaches. Mamm Genome 29:593-602
Agnihothram, Sudhakar; Menachery, Vineet D; Yount Jr, Boyd L et al. (2018) Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform. J Virol 92:
Johnson, Bryan A; Graham, Rachel L; Menachery, Vineet D (2018) Viral metagenomics, protein structure, and reverse genetics: Key strategies for investigating coronaviruses. Virology 517:30-37
Gunn, Bronwyn M; Jones, Jennifer E; Shabman, Reed S et al. (2018) Ross River virus envelope glycans contribute to disease through activation of the host complement system. Virology 515:250-260
Kollmus, Heike; Pilzner, Carolin; Leist, Sarah R et al. (2018) Of mice and men: the host response to influenza virus infection. Mamm Genome 29:446-470
Gorman, Matthew J; Caine, Elizabeth A; Zaitsev, Konstantin et al. (2018) An Immunocompetent Mouse Model of Zika Virus Infection. Cell Host Microbe 23:672-685.e6
Baxter, Victoria K; Heise, Mark T (2018) Genetic control of alphavirus pathogenesis. Mamm Genome 29:408-424
Chow, Kwan T; Driscoll, Connor; Loo, Yueh-Ming et al. (2018) IRF5 regulates unique subset of genes in dendritic cells during West Nile virus infection. J Leukoc Biol :
Gralinski, Lisa E; Sheahan, Timothy P; Morrison, Thomas E et al. (2018) Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. MBio 9:

Showing the most recent 10 out of 77 publications