This Program Project application """"""""The Role of mRNA Decay in the Immune System"""""""" is designed to coordinate the efforts of investigators who have been studying post-transcriptional regulation, in particular, the mechanisms involved in mRNA turnover. The program is to be directed by Sidney Pestka, chair of the Department of Molecular Genetics, Microbiology and Immunology and an investigator with a long term interest in interferons, cytokines, signal transduction and mRNA turnover. The Program Project consists of five projects: 1. Adherence Activated Monocyte Genes;2. ARE &non-ARE Pathways Regulating CD154 mRNA Stability;3. Translational Regulation by the TNF Alpha AU-rich Element;4. Regulation of Cytokine Gene Expression by mRNA Turnover;5: Regulation of RANKL Expression in T-Lymphocytes. Four of the individuals have experience in the study of mRNA lifetime;two of the investigators are immunologists. The Program Project contains an administrative core and six small cores to make the work efficient and effective. The cores are: A) Flow Cytometry Facility;B) Real-Time PCR Facility;C) Imaging Facility;D) Irradiation Facility;E) DNA Synthesis &Sequencing Facility;F) Real time Fluorescence Resonance Energy Facility. The overall aim of this application is to understand how mRNA turnover controls various steps in immune activation and differentiation during immune responses. One of the fast methods to control changes in protein expression is by modification of the rate of mRNA decay, a post-transcriptional process. Understanding the role of mRNA turnover in regulation of the immune system will provide an opportunity to develop new therapeutics to control these processes and treat a variety of diseases such as rheumatoid arthritis and other immune disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
3P01AI057596-05S1
Application #
7925367
Study Section
Special Emphasis Panel (ZAI1-CL-I (S2))
Program Officer
Mallia, Conrad M
Project Start
2009-09-22
Project End
2010-06-30
Budget Start
2009-09-26
Budget End
2010-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$655,862
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Genetics
Type
Schools of Medicine
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Krause, Christopher D; Izotova, Lara S; Pestka, Sidney (2013) Analytical use of multi-protein Fluorescence Resonance Energy Transfer to demonstrate membrane-facilitated interactions within cytokine receptor complexes. Cytokine 64:298-309
Zhang, J; Roberts, A I; Liu, C et al. (2013) A novel subset of helper T cells promotes immune responses by secreting GM-CSF. Cell Death Differ 20:1731-41
Krause, Christopher D; Digioia, Gina; Izotova, Lara S et al. (2013) Improving the spectral analysis of Fluorescence Resonance Energy Transfer in live cells: application to interferon receptors and Janus kinases. Cytokine 64:272-85
Krause, Christopher D; Digioia, Gina; Izotova, Lara S et al. (2013) Ligand-independent interaction of the type I interferon receptor complex is necessary to observe its biological activity. Cytokine 64:286-97
Wu, Xiangyue; Chesoni, Sandra; Rondeau, Gaelle et al. (2013) Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs. Nucleic Acids Res 41:2644-58
Krause, Christopher D; Izotova, Lara S; Ren, Gwangwen et al. (2011) Efficient co-expression of bicistronic proteins in mesenchymal stem cells by development and optimization of a multifunctional plasmid. Stem Cell Res Ther 2:15
Matus-Nicodemos, Rodrigo; Vavassori, Stefano; Castro-Faix, Moraima et al. (2011) Polypyrimidine tract-binding protein is critical for the turnover and subcellular distribution of CD40 ligand mRNA in CD4+ T cells. J Immunol 186:2164-71
Yamaza, T; Ren, G; Akiyama, K et al. (2011) Mouse mandible contains distinctive mesenchymal stem cells. J Dent Res 90:317-24
Sarkar, Srijata; Han, Junfeng; Sinsimer, Kristina S et al. (2011) RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IkappaB kinase complex in monocytes. Mol Cell Biol 31:602-15
Knapinska, Anna M; Gratacós, Frances M; Krause, Christopher D et al. (2011) Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation. Mol Cell Biol 31:1419-31

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