This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Innate immunity serves as an essential first-line of defense against microbial pathogens and also influences the nature of the subsequent adaptive immune response. Phagocytic cells, such as macrophages and neutrophils, play key roles in innate immunity because of their ability to recognize, ingest, and destroy many pathogens by oxidative and non-oxidative mechanisms. These phagocytes express the NADPH oxidase, a multi-protein enzyme complex that generates reactive oxygen species (ROS) during the host immune responses. Although essential to host defense, ROS are highly-reactive and can also damage host tissue. It is therefore essential that we understand the regulatory aspects of the host inflammatory response, in order to define better strategies for controlling inflammation. Recently, we made the exciting observation that the oncogenic transcription factor, PLAGL2, plays a role in the regulation of the NADPH oxidase. Although PLAGL2 has been shown to be involved in carcinogenesis, virtually nothing is known regarding the identity of PLAGL2 target genes or the mechanisms of PLAGL2 gene regulation in vivo and nothing is known about the role of PLAGL2 in phagocytic leukocytes. Based on our studies, we hypothesize that PLAGL2 is an important regulatory component in innate immune responses. The proteomics-based approach outlined in this proposal incorporates 2D-DIGE, 2D-Zdye and LC-MS/MS to elucidate the role of PLAGL2 in phagocytic leukocytes by 1) identifying additional PLAGL2 target genes and the signaling networks involved, and 2) the mechanisms whereby PLAGL2 regulates inflammation via protein-protein interactions. This work aims to lead to a systems biology analysis of the signaling pathways and mechanisms in the host inflammatory response, in collaboration with systems researchers at MSU and Pacific Northwest National Lab (PNNL). Understanding the basic systems biology of the host inflammatory response, as regulated by PLAGL2, is expected to uncover unique regulatory mechanisms that will provide the foundation for the development of improved therapies for influencing inflammation and disease pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR024237-04
Application #
8359569
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2011-03-01
Project End
2012-02-29
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
4
Fiscal Year
2011
Total Cost
$175,246
Indirect Cost
Name
Montana State University - Bozeman
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
McCutchen, Carley N; Zignego, Donald L; June, Ronald K (2017) Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments. J Biomech 64:49-58
Folsom, James Patrick; Carlson, Ross P (2015) Physiological, biomass elemental composition and proteomic analyses of Escherichia coli ammonium-limited chemostat growth, and comparison with iron- and glucose-limited chemostat growth. Microbiology 161:1659-70
Weaver Jr, Alan J; Shepard, Joyce B; Wilkinson, Royce A et al. (2014) Antibacterial activity of THAM Trisphenylguanide against methicillin-resistant Staphylococcus aureus. PLoS One 9:e97742
Bernstein, Hans C; Carlson, Ross P (2014) Design, construction, and characterization methodologies for synthetic microbial consortia. Methods Mol Biol 1151:49-68
Blosser, Sara J; Merriman, Brittney; Grahl, Nora et al. (2014) Two C4-sterol methyl oxidases (Erg25) catalyse ergosterol intermediate demethylation and impact environmental stress adaptation in Aspergillus fumigatus. Microbiology 160:2492-506
Heinemann, Joshua; Hamerly, Timothy; Maaty, Walid S et al. (2014) Expanding the paradigm of thiol redox in the thermophilic root of life. Biochim Biophys Acta 1840:80-5
Fonner, Brittany A; Tripet, Brian P; Lui, Mengyao et al. (2014) ¹H, ¹³C, ¹?N backbone and side chain NMR resonance assignments of the N-terminal NEAr iron transporter domain 1 (NEAT 1) of the hemoglobin receptor IsdB of Staphylococcus aureus. Biomol NMR Assign 8:201-5
Duffus, Benjamin R; Ghose, Shourjo; Peters, John W et al. (2014) Reversible H atom abstraction catalyzed by the radical S-adenosylmethionine enzyme HydG. J Am Chem Soc 136:13086-9
Mason, Katelyn E; Tripet, Brian P; Parrott, David et al. (2014) ¹H, ¹³C, ¹?N backbone and side chain NMR resonance assignments for the N-terminal RNA recognition motif of the HvGR-RBP1 protein involved in the regulation of barley (Hordeum vulgare L.) senescence. Biomol NMR Assign 8:149-53
Chung, Dawoon; Thammahong, Arsa; Shepardson, Kelly M et al. (2014) Endoplasmic reticulum localized PerA is required for cell wall integrity, azole drug resistance, and virulence in Aspergillus fumigatus. Mol Microbiol 92:1279-98

Showing the most recent 10 out of 39 publications