This program project seeks to systematically address crucial questions about the interplay between innate responses to HIV-1 infection. We anticipate to dissect the complete repertoire of cellular sensors and effectors involved in the innate signaling pathways that respond to HIV-1. Moreover, the rate-limiting components and the crosstalk between these pathways will provide critical information about important key players in the response to HIV-1. We also anticipate to acquire a novel understanding of the kinetics of HIV-1 infection regulated by these pathways and the effect of these pathways on the clinical outcome of infection. The systems-level understanding of these processes will be used to construct mathematical models that can predict the behavior of these pathways to HIV-1 infection. These integrated pieces of information about the host-pathogen interface will be invaluable for future optimization of antiviral and vaccine approaches. Scientific projects taking place within the scope of the Program Project will rely to a great extent on largescale production of viruses and siRNA, shRNA and cDNA technologies in high-throughput format as a result of the genomics nature of the approach. The goal of the Molecular Virology and Systems Biology Screening Core is to support the scientists in all aspects ofthe large-scale and system-biology screening approaches by providing state-of-the-art cellular genomics technologies and molecular virology tools. The PI has significant experience in the field of systems-biology. Dr. KOnig will provide her collective expertise in Virology for over 11 years and her experience in developing and employing systems-biology screening tools. These studies are expected to provide global molecular insight into cellular and viral processes that regulate early immune responses to HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
7P01AI090935-05
Application #
8707335
Study Section
Special Emphasis Panel (ZAI1-EC-A)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$183,771
Indirect Cost
$42,786
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Hansen, Maike M K; Desai, Ravi V; Simpson, Michael L et al. (2018) Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability. Cell Syst 7:384-397.e6
Jain, Prashant; Boso, Guney; Langer, Simon et al. (2018) Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu. Cell Rep 22:2493-2503
Hansen, Maike M K; Wen, Winnie Y; Ingerman, Elena et al. (2018) A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization. Cell 173:1609-1621.e15
Alvarez, Raymond A; Maestre, Ana M; Law, Kenneth et al. (2017) Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG. JCI Insight 2:e88226
Park, Ryan J; Wang, Tim; Koundakjian, Dylan et al. (2017) A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Nat Genet 49:193-203
Ball, K Aurelia; Johnson, Jeffrey R; Lewinski, Mary K et al. (2016) Non-degradative Ubiquitination of Protein Kinases. PLoS Comput Biol 12:e1004898
Hultquist, Judd F; Schumann, Kathrin; Woo, Jonathan M et al. (2016) A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep 17:1438-1452
Cheng, Zhang; Hoffmann, Alexander (2016) A stochastic spatio-temporal (SST) model to study cell-to-cell variability in HIV-1 infection. J Theor Biol 395:87-96
Guo, Haitao; K├Ânig, Renate; Deng, Meng et al. (2016) NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses. Cell Host Microbe 19:515-528
Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain et al. (2016) Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity 44:46-58

Showing the most recent 10 out of 94 publications