A novel computational model of B cell signaling and activation
B 细胞信号传导和激活的新型计算模型
基本信息
- 批准号:8120735
- 负责人:
- 金额:$ 28.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-05 至 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffinityAntigensB-Cell ActivationB-LymphocytesBindingBiologicalCell membraneCell surfaceCellsComplexComputer SimulationCouplingCrowdingDataDiffusionDiscriminationDiseaseFunctional disorderFutureGoalsImageImmuneImmune responseImmunologistIn VitroInvestigationLaboratoriesMapsMeasurableMediatingMembraneMethodsModelingOther GeneticsPattern FormationPhysiologicalPositioning AttributeProcessReactionReceptors, Antigen, B-CellRegulationResearchRunningSchemeSignal PathwaySignal TransductionSynapsesSystemTechniquesWorkcomputer programin vivoinsightnovelpredictive modelingpublic health relevancereceptorresearch studyresponsesimulationsingle moleculesynaptogenesistool
项目摘要
DESCRIPTION (provided by applicant): One of the long-term goals of our laboratory is to develop and combine different analytical and computer simulation techniques into a unified computational modeling scheme to investigate B cell responses. We are developing this proposed in silico model specifically to investigate the mechanism of B cell immune recognition, signaling, and activation. Computational modeling will be carried out synergistically with biological experiments in an iterative manner. The stochastic character of our model enables us to capture any cell-to-cell stochastic fluctuations present in the system. We rigorously map the probabilistic parameters of our model to the reaction and diffusion rate constants that are measurable in biological experiments. This proposed work is going to deliver the following: (i) computational and theoretical approaches to investigate B cell receptor clustering in the form of immune synapses and caps for the cases of membrane-bound and soluble antigens respectively, (ii) a computer model of receptor diffusion in a heterogeneous B cell membrane in parallel with single molecules tracking studies, (iii) a computational model of B cell signaling that can be used by B cell immunologists to study B cell antigen recognition, signaling, and activation under a plethora of different physiological conditions by running controlled in silico experiments. Our approach will also be able to address the question of how B cells generate a graded response by recognizing antigens of widely varying affinities.
PUBLIC HEALTH RELEVANCE: The B cell immune response is a complex process and a precise mechanism of B cell signaling and activation is not easy to investigate from in vivo and in vitro experiments alone. In the proposed research, we plan to develop computer models of B cell antigen recognition, signaling, and activation. Our computer model will help elucidate the fundamental regulation mechanisms underlying the B cell immune response and could potentially be applied to investigate B cell mediated diseases.
描述(由申请人提供):我们实验室的长期目标之一是开发和联合收割机不同的分析和计算机模拟技术到一个统一的计算建模方案,以调查B细胞的反应。我们正在开发这个提出的计算机模型,专门研究B细胞免疫识别,信号传导和激活的机制。计算建模将以迭代方式与生物实验协同进行。我们的模型的随机特性使我们能够捕获系统中存在的任何细胞到细胞的随机波动。我们严格地将我们模型的概率参数映射到生物实验中可测量的反应和扩散速率常数。这项拟议的工作将实现以下目标:(i)分别针对膜结合抗原和可溶性抗原的情况研究免疫突触和帽形式的B细胞受体聚集的计算和理论方法,(ii)与单分子追踪研究平行的异质B细胞膜中受体扩散的计算机模型,(iii)B细胞信号传导的计算模型,其可由B细胞免疫学家用于通过运行受控的计算机模拟实验来研究在大量不同生理条件下的B细胞抗原识别、信号传导和活化。我们的方法也将能够解决B细胞如何通过识别亲和力差异很大的抗原来产生分级反应的问题。
公共卫生相关性:B细胞免疫应答是一个复杂的过程,并且仅从体内和体外实验不容易研究B细胞信号传导和活化的精确机制。在拟议的研究中,我们计划开发B细胞抗原识别、信号传导和激活的计算机模型。我们的计算机模型将有助于阐明B细胞免疫应答的基本调控机制,并可能被应用于研究B细胞介导的疾病。
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)
Correlating anomalous diffusion with lipid bilayer membrane structure using single molecule tracking and atomic force microscopy.
- DOI:10.1063/1.3596377
- 发表时间:2011-06
- 期刊:
- 影响因子:0
- 作者:Michael J. Skaug;R. Faller;M. Longo
- 通讯作者:Michael J. Skaug;R. Faller;M. Longo
Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement.
B 细胞对膜抗原亲和力的区分需要动力学校对优于串行接合。
- DOI:10.1038/cmi.2011.29
- 发表时间:2012
- 期刊:
- 影响因子:24.1
- 作者:Tsourkas,PhilipposK;Liu,Wanli;Das,SomkanyaC;Pierce,SusanK;Raychaudhuri,Subhadip
- 通讯作者:Raychaudhuri,Subhadip
The network of receptors characterize B cell receptor micro- and macroclustering in a Monte Carlo model.
受体网络表征了蒙特卡罗模型中 B 细胞受体微观和宏观聚类的特征。
- DOI:10.1021/jp9079074
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Reddy,ASrinivas;Chilukuri,Sandeep;Raychaudhuri,Subhadip
- 通讯作者:Raychaudhuri,Subhadip
Metastability in pixelation patterns of coexisting fluid lipid bilayer phases imposed by e-beam patterned substrates.
电子束图案化基底施加的共存流体脂质双层相的像素化图案的亚稳定性。
- DOI:10.1039/c2sm27027g
- 发表时间:2013
- 期刊:
- 影响因子:3.4
- 作者:Ogunyankin,MariaO;Longo,MarjorieL
- 通讯作者:Longo,MarjorieL
Lipid domain pixelation patterns imposed by e-beam fabricated substrates.
由电子束制造的基底施加的脂质域像素化图案。
- DOI:10.1021/la3008415
- 发表时间:2012
- 期刊:
- 影响因子:0
- 作者:Ogunyankin,MariaO;Torres,Andrea;Yaghmaie,Frank;Longo,MarjorieL
- 通讯作者:Longo,MarjorieL
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CRAIG J. BENHAM的其他文献
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{{ truncateString('CRAIG J. BENHAM', 18)}}的其他基金
INFERRING CHROMOSOME ARCHITECTURE FROM GENOMIC SEQUENCE
从基因组序列推断染色体结构
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6397760 - 财政年份:2000
- 资助金额:
$ 28.05万 - 项目类别:
INFERRING CHROMOSOME ARCHITECTURE FROM GENOMIC SEQUENCE
从基因组序列推断染色体结构
- 批准号:
6095266 - 财政年份:2000
- 资助金额:
$ 28.05万 - 项目类别:
INFERRING CHROMOSOME ARCHITECTURE FROM GENOMIC SEQUENCE
从基因组序列推断染色体结构
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6536467 - 财政年份:2000
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$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
2749897 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
2459436 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
2184484 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
2184482 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
6018880 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
2184483 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
THEORETICAL ANALYSIS OF DNA SUPERHELICAL EQUILIBRIA
DNA超螺旋平衡的理论分析
- 批准号:
3306556 - 财政年份:1993
- 资助金额:
$ 28.05万 - 项目类别:
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