Understanding Mechanisms of Robust Information Processing by NF-kappaB

了解 NF-kappaB 鲁棒信息处理的机制

基本信息

批准号：
9884554
负责人：
Savas Tay
金额：
$ 35.53万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884554
关键词：
Affect Attention Autoimmune Diseases Autoimmunity Back Bacteria Biological Biological Models Biology Buffers CRISPR/Cas technology Cell Culture Techniques Cells Cellular biology Chronic Complex Data Decision Making Disease Double-Stranded RNA Environment Feedback Fibroblasts Gene Expression Gene Expression Regulation Immune Immune response Immune signaling Immunity Individual Infection Inflammation Knock-out Ligands Malignant Neoplasms Maps Measurement Measures Medical MicroRNAs Microfluidic Microchips Microfluidics Modeling Molecular NF-kappa B Nature Noise Organism Output Pathway interactions Pharmacology Positioning Attribute Process Reporting Role Signal Pathway Signal Transduction Signaling Molecule Small Interfering RNA Stimulus System TNF gene Techniques Testing Therapeutic Tissues Translations Virus Diseases Zymosan cytokine digital experience experimental study fungus improved information processing insight knock-down mathematical methods mathematical model network architecture operation pathogen prevent receptor response simulation single cell analysis

项目摘要

Understanding Mechanisms of Robust Information Processing by NF-κB A major open question in biology is how do cells operate robustly despite ever-present biological noise? Inputs received by cells are unavoidably noisy due to variable translation and secretion of signaling factors, propagation in tissues and stochastic fluctuations in molecular concentrations. Yet, somehow cells are able to accurately process these noisy inputs and create appropriate responses regularly. This proposal aims to answer this fundamental question by studying the effect of noise on gene regulation by the well-known and medically important innate immune signaling pathway NF-B. Attempts at understanding dynamic gene regulation by NF-B and the molecular mechanisms that deal with noise have generally been hampered by significant cell-to-cell variability (requiring single cell analyses), and technical limitations in studying live cells under dynamical signals. Here, we will combine our experience in NF-B signaling, established microfluidic cell culture techniques and mathematical modeling to study this most interesting problem in single cells. Our lab is uniquely positioned to explore and answer this new field, as we have spent the last 10 years constructing and improving the experimental and mathematical methods to study the effect of noise in cellular decision making. Answering this question will have a profound impact on both our basic understanding of cellular decision-making processes, as well as implications in preventing and treating diseases like infection, autoimmunity and cancer.

了解 NF-κB 鲁棒信息处理的机制生物学中一个主要的悬而未决的问题是，尽管生物噪音始终存在，细胞如何稳健运行？由于信号因子的翻译和分泌的可变性，细胞接收到的输入不可避免地存在噪音，然而，细胞在组织中的传播和分子浓度的随机波动却是能够的。准确处理这些噪音输入并定期创建适当的响应。通过研究噪音对基因调控的影响来回答这个基本问题医学上重要的先天免疫信号通路 NF-β 尝试了解动态基因。 NF-κB 的调节和处理噪音的分子机制通常受到以下因素的阻碍：显着的细胞间差异（需要单细胞分析）以及活细胞研究的技术限制在这里，我们将结合我们在 NF-κB 信号传导方面的经验，建立了微流控细胞培养技术和数学建模来研究这个最有趣的问题我们的实验室在探索和回答这个新领域方面处于独特的地位，因为我们已经度过了最后的时光。 10年构建和完善实验和数学方法来研究效果回答这个问题将对我们的基本决策产生深远的影响。了解细胞决策过程以及对预防和治疗的影响感染、自身免疫和癌症等疾病。