Quantification modelling and analysis of molecular dynamics patterning and signalling in the NK synapse.

NK 突触分子动力学模式和信号传导的量化建模和分析。

• 批准号: BB/D011663/1
• 负责人: Nigel Burroughs
• 金额: $ 102万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD011663%2F1
• 关键词: Quantification; modelling; analysis; molecular; dynamics

Biological systems function by coordinated signalling and communication between cells, signals which determine cell function and response. The immune system is one of the best studied as regards signalling between cells with both signalling via soluble mediators and cell:cell contact. Such signalling regulates and directs the immune system response to pathogen exposure where an inappropriate response can lead to disease and death. Signalling during cell:cell contact results in formation of a macroscopic signalling interface with patterning on the scale of microns of various receptors, the simplest pattern observed being a bull's-eye configuration. A theory for the mechanism of this patterning has been suggested and a mathematical model available for simulation which gives realistic results, a model that emphasises the role of the cell:cell interface environment on signalling. We will test this model by measuring a number of model parameters, varying from cell elasticity to chemical reaction affinities, and verify model predictions. This will be achieved by sophisticated imaging using green fluorescent jelly fish protein fused to proteins of interest, and leading edge image analysis. The system we will be studying is of immense importance in medicine and immunology.

生物系统通过协调的信号传导和电池之间的通信，确定细胞功能和响应的信号的功能。免疫系统是通过可溶性介质和细胞传导的细胞之间的信号传导：细胞的信号传导：细胞接触：。这种信号调节并指导免疫系统对病原体暴露的反应，而病原体暴露会导致疾病和死亡。细胞中的信号传导：细胞接触导致形成宏观信号界面，并在各种受体的微米尺度上进行图案，这是最简单的模式，观察到的是公牛的眼睛构型。已经提出了有关这种模式的机理的理论，并提供了一个用于仿真的数学模型，该模型可提供逼真的结果，该模型强调了细胞：细胞界面环境在信号传导中的作用。我们将通过测量许多模型参数来测试该模型，从细胞弹性到化学反应亲和力不等，并验证模型预测。这将通过使用与感兴趣的蛋白质和前沿图像分析的绿色荧光果冻鱼蛋白进行复杂成像来实现。我们将研究的系统在医学和免疫学中至关重要。

项目成果

Intrigue at the immune synapse

• DOI: 10.1038/scientificamerican0206-48
• 发表时间: 2006-02-01
• 期刊: SCIENTIFIC AMERICAN
• 影响因子: 3
• 作者: Davis, DM

Remodelling of cortical actin where lytic granules dock at natural killer cell immune synapses revealed by super-resolution microscopy.

• DOI: 10.1371/journal.pbio.1001152
• 发表时间: 2011-09
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Brown AC;Oddos S;Dobbie IM;Alakoskela JM;Parton RM;Eissmann P;Neil MA;Dunsby C;French PM;Davis I;Davis DM
• 通讯作者: Davis DM

Ligand dimensions are important in controlling NK-cell responses.

• DOI: 10.1002/eji.201040335
• 发表时间: 2010-07
• 期刊: EUROPEAN JOURNAL OF IMMUNOLOGY
• 影响因子: 5.4
• 作者: Brzostek, Joanna;Chai, Jian-Guo;Gebhardt, Friedemann;Busch, Dirk H.;Zhao, Rui;van der Merwe, P. Anton;Gould, Keith G.
• 通讯作者: Gould, Keith G.

An improved strip FRAP method for estimating diffusion coefficients: correcting for the degree of photobleaching.

用于估计扩散系数的改进条带 FRAP 方法：校正光漂白程度。

• DOI: 10.1111/j.1365-2818.2009.03347.x
• 发表时间: 2010
• 期刊: Journal of microscopy
• 影响因子: 2
• 作者: Yang J