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。

基本信息

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

项目摘要

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.

生物系统通过细胞之间协调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。免疫系统是细胞间信号传导研究最充分的系统之一，既通过可溶性介质进行信号传导，又通过细胞与细胞接触进行信号传导。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能导致疾病和死亡。细胞与细胞接触过程中的信号传导导致宏观信号传导界面的形成，其中各种受体具有微米级的图案，观察到的最简单的图案是牛眼结构。已经提出了这种模式机制的理论，以及可用于模拟的数学模型，该模型给出了真实的结果，该模型强调了细胞：细胞界面环境对信号传导的作用。我们将通过测量从细胞弹性到化学反应亲和力等一系列模型参数来测试该模型，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以及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具有极其重要的意义。