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Quantitative modeling of the phenotypic variability of individual T cells and the

个体 T 细胞表型变异的定量建模和

基本信息

批准号：
8306678
负责人：
Gregoire Altan-Bonnet
金额：
$ 48.89万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-05 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306678
关键词：
Accounting Affect Agonist Antigen Receptors Antigens Autoantigens Biological Biological Assay Blast Cell Cell Proliferation Cells Cessation of life Chimeric Proteins Communication Computer Simulation Computers Conflict (Psychology)Coupled Cues Cytokine Signaling Data Discrimination Down-Regulation Feedback Fluorescence Frequencies Genetic Goals Heterogeneity IL2 gene Immune System Diseases Immune response Immune system Individual Infection Interleukin-15 Interleukin-2 Knowledge Libraries Ligands Maps Measurement Methods Modeling Monitor Mutate Pathway interactions Peripheral Phenotype Phosphotransferases Physiological Population Population Heterogeneity Property Proteins RNA Interference Receptor Signaling Regulation Regulatory Pathway Regulatory T-Lymphocyte Research Shapes Signal Pathway Signal Transduction Signaling Protein Sorting - Cell Movement Specificity Staging System T cell response T-Cell Activation T-Lymphocyte Testing Tissues Translating Update Variant Work analog antigen challenge base cDNA Library cancer immunotherapy chemokine clinical application cytokine density deprivation digital overexpression pathogen protein expression quorum sensing receptor expression response synergism thymocyte

项目摘要

Our long-term goal is to probe theoretically and experimentally how reliable immune responses emerge at the system level from the unreliable responses of individual T cells. Our first project aims at probing how heterogeneity in the expression levels of key signaling proteins generates phenotypic variability in T cells' responsiveness to ligands. We will also probe how such stochasticity of signaling responses translates into functional phenotypic variability. Our second aim tests how multiplexed signals (e.g. T cell ligands and IL15 cytokine) can activate signaling crosstalks that modulate the levels and/or activity of key signaling proteins and make T cells hyperresponsive to self-derived ligands. Our third aim probes how cytokine regulation integrates cell variability in antigen response at the individual cell level towards a regulated collective response. This project focuses on Interleukin-2 as a critical cytokine that controls quorum sensing among effector T cells and suppression by regulatory T cells. Our approach is fundamentally interdisciplinary with concomitant computational modeling and experimental testing. It consists in making and validating theoretical predictions to quantify and control how immune responses emerge as dynamically- and collectively-regulated properties of individual T cells.

我们的长期目标是从理论上和实验上探索如何可靠地免疫在系统层面上的反应来自于个体T的不可靠反应，细胞我们的第一个项目旨在探讨在表达水平的异质性，关键信号蛋白在T细胞对免疫应答的反应中产生表型变异，配体。我们还将探讨这种信号反应的随机性如何转化为功能表型变异性我们的第二个目的是测试多重信号（例如T细胞配体和IL 15）如何在细胞内表达。细胞因子）可以激活信号传导串扰，所述信号传导串扰调节关键细胞因子的水平和/或活性。信号蛋白，使T细胞对自身衍生的配体反应过度。我们的第三个目标是探索细胞因子调节如何整合抗原中的细胞变异性。在个体细胞水平上的反应朝向调节的集体反应。这个项目白细胞介素-2作为一种关键的细胞因子，控制群体感应，效应T细胞和调节性T细胞的抑制。我们的方法从根本上讲是跨学科的，建模和实验测试。它包括制定和验证理论预测，以量化和控制免疫反应如何动态地出现，个体T细胞的集体调节特性。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fluorescence correlation spectroscopy in living cells: a practical approach.

DOI：
10.1002/0471143030.cb0424s45
发表时间：
2009-12-01
期刊：
Current protocols in cell biology
影响因子：
0
作者：
Altan-Bonnet, Nihal;Altan-Bonnet, Gregoire
通讯作者：
Altan-Bonnet, Gregoire

Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.

DOI：
10.1016/j.molcel.2017.05.011
发表时间：
2017-06-01
期刊：
Molecular cell
影响因子：
16
作者：
Oyler-Yaniv J;Oyler-Yaniv A;Shakiba M;Min NK;Chen YH;Cheng SY;Krichevsky O;Altan-Bonnet N;Altan-Bonnet G
通讯作者：
Altan-Bonnet G

T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens.

T 细胞整合局部和全局线索来区分结构相似的抗原。

DOI：
10.1016/j.celrep.2015.04.051
发表时间：
2015
期刊：
Cell reports
影响因子：
8.8
作者：
Voisinne,Guillaume;Nixon,BrianaG;Melbinger,Anna;Gasteiger,Georg;Vergassola,Massimo;Altan-Bonnet,Grégoire
通讯作者：
Altan-Bonnet,Grégoire

Noise-driven causal inference in biomolecular networks.

DOI：
10.1371/journal.pone.0125777
发表时间：
2015
期刊：
PloS one
影响因子：
3.7
作者：
Prill RJ;Vogel R;Cecchi GA;Altan-Bonnet G;Stolovitzky G
通讯作者：
Stolovitzky G

Phosphatidylserine vesicles enable efficient en bloc transmission of enteroviruses.

DOI：
10.1016/j.cell.2015.01.032
发表时间：
2015-02-12
期刊：
Cell
影响因子：
64.5
作者：
Chen YH;Du W;Hagemeijer MC;Takvorian PM;Pau C;Cali A;Brantner CA;Stempinski ES;Connelly PS;Ma HC;Jiang P;Wimmer E;Altan-Bonnet G;Altan-Bonnet N
通讯作者：
Altan-Bonnet N