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Combining Computational and Experimentation to Interrogate NF-kappaB Signaling

结合计算和实验来探究 NF-kappaB 信号传导

基本信息

批准号：
8100175
负责人：
Markus W Covert
金额：
$ 24.15万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-18 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8100175
关键词：
Address Autocrine Communication B-Cell Lymphomas B-Lymphocytes Baltimore Behavior Binding Sites Biochemical Cells Chimeric Proteins Complex Computer Simulation Computing Methodologies Development Exhibits Gene Chips Gene Expression Gene Targeting Genes Investigation Language Malignant Neoplasms Methods Microscopy Modeling Molecular Monitor NF-kappa B Paracrine Communication Pathway Analysis Pathway interactions Phase Population Principal Investigator Property Receptor Activation Receptors, Antigen, B-Cell Repression Research Role Signal Transduction Specific qualifier value Specificity Stimulus Study models System Systems Biology TLR4 gene Techniques Time Work abstracting autocrine base cancer type large cell Diffuse non-Hodgkin&apos s lymphoma models and simulation network models p65 programs reconstruction research study response time use transcription factor tumor progression

项目摘要

DESCRIPTION (provided by applicant): The purpose of this research is to use systems biology approaches to understand the specificity and temporal mechanisms that govern activation of transcription factor NF-kappaB, as well as how NF-kappaB evokes a transcriptional response, in order to better understand progression of certain types of cancer. Systems-based and computational approaches are particularly well-suited to address this issue. Using a combined computational modeling/experimental approach, we were able to characterize a previously-unknown part of the pathways which led from LPS stimulation to NF-kappaB activation. This approach also led to the explanation of a complex behavior: the observed stable activation of NF-kappaB under LPS stimulation. Moving forward, we propose to continue using an integrated approach to study the NF-kappaB network at several levels of abstraction. Our Specific Aims are to: (1) reconstruct and analyze a network model of the entire known NF-kappaB signaling and transcriptional network; (2) derive a detailed description and model of the gene expression response to NF-kappaB activation; (3) build a quantitative description of B cell-related NF-kappaB activation dynamics into a detailed computational model; and (4) observe and model NF-kappaB-related activation and autocrine/paracrine signaling in single cells. PLAIN LANGUAGE SUMMARY: Advances in our ability to build computer models, and to use model predictions to guide experiments, have great potential in helping us to understand cancer progression. We propose to use computer modeling and experiments to help us understand the NF-kappaB signaling network and its role in cancer development, particularly with regard to diffuse large B cell lymphomas.

描述（由申请人提供）：本研究的目的是使用系统生物学方法来了解控制转录因子NF-kappaB激活的特异性和时间机制，以及NF-kappaB如何引发转录反应，以便更好地了解某些类型癌症的进展。基于系统的方法和计算方法特别适合解决这个问题。