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.

生物系统通过协调细胞之间的信号传导和通信来发挥作用，这些信号决定细胞的功能和反应。免疫系统是关于细胞之间的信号传导的最好的研究之一，其中信号传导通过可溶性介质和细胞：细胞接触。这种信号传导调节和指导免疫系统对病原体暴露的反应，其中不适当的反应可导致疾病和死亡。细胞：细胞接触期间的信号传导导致形成宏观信号传导界面，其具有各种受体的微米级图案，观察到的最简单图案是靶心构型。这种模式化的机制的理论已被提出，并提供了一个数学模型的模拟，给出了现实的结果，一个模型，强调细胞的作用：细胞界面环境的信号。我们将通过测量一些模型参数来测试这个模型，从细胞弹性到化学反应亲和力，并验证模型预测。这将通过使用与感兴趣的蛋白质融合的绿色荧光水母蛋白的复杂成像和前沿图像分析来实现。我们将要研究的系统在医学和免疫学中非常重要。

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