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在免疫突触蛋白在细胞膜上的喷雾型态分布统计分析
Statistical analysis of protein patternation on cell membranes during immunological synapse |
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| 课程网址: |
http://videolectures.net/licsb2010_miloserdov_sap/
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| 主讲教师: |
Vladimir Miloserdov
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| 开课单位: |
华威大学
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| 开课时间: |
2010-05-06
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| 课程语种: |
英语
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| 中文简介: |
考虑了两个不同实验的统计分析。它们都与理解在免疫细胞膜和抗原呈递细胞的膜之间的接触界面中参与形成蛋白质复合物和分子的有组织模式的分子分布背后的机制有关。这种模式称为免疫突触。在第一个实验中，T细胞粘附在脂质双层的平坦表面上。在双层的表面上存在两种类型的分子。它们用不同的颜色进行荧光标记，因此可以使用显微镜观察它们的分布。在接触期间，一种类型的分子结合，而第二种类型的分子保持未结合。这导致不同类型分子的分离并形成可以使用共聚焦显微镜观察和扫描的突触图案。在脂质双层的情况下，接触界面是平坦的，并且整个接触界面可以作为单个图像扫描。第二个实验涉及与靶抗原呈递细胞形成突触的NK细胞。再次使用双色荧光标记，并且可以使用共聚焦显微镜观察细胞 - 细胞接触界面上的类似蛋白质图案。与第一个实验的主要区别在于成像技术，而不是单个图像，沿着与突触界面大致平行的同一轴形成一系列共焦图像。结果，相互作用细胞的一叠截面荧光图像被考虑用于定量分析。在两个实验中，可以在突触模式的形成过程中观察标记分子的分离。就荧光强度值而言，这表示为不同颜色荧光之间的强负相关。我们引入了一个基于大小排除假设的模型，该模型解释了由于单分子和键的弹性特性以及细胞膜的特性而导致的分子的相互分离。基于该模型，开发了用于荧光图像的贝叶斯统计分析的计算算法，以便估计不能明确测量的相关物理参数。
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| 课程简介: |
A statistical analysis of two different experiments is considered. Both of them are related to understanding the mechanism behind the distribution of molecules involved in formation of organized patterns of protein complexes and molecules in the contact interface between the membranes of an immune cell and an antigen presenting cell. Such patterns are called immunological synapses. In the first experiment a T-cell is adhering to the flat surface of a lipid bilayer. There are molecules of two types on the surface of the bilayer. They are fluorescently labelled with different colours so their distribution can be observed using microscope. During the contact molecules of one type are binding while second type molecules stay unbound. This results in segregation of different type molecules and forming a synapse pattern that can be observed and scanned using confocal microscopy. In the case of lipid bilayer the contact interface is flat and the whole contact interface can be scanned as a single image. The second experiment deals with NK-cells forming synapses with target antigen presenting cells. Two-colour fluorescent labelling is used again and a similar protein patternation on the cell-cell contact interface can observed using confocal microscopy. The main difference with the first experiment is in imaging technique as instead of a single image a series of confocal images is made along the same axis which is approximately parallel to the synapse interface. As a result a stack of cross-section fluorescence images of the interacting cells is considered for the quantitative analysis. In both experiments it is possible to observe the segregation of labelled molecules during the formation of the synapse pattern. In terms of fluorescence intensity values this is expressed in strong negative correlation between different colour fluorescence. We introduce a model based on the hypothesis of exclusion by size which explains the mutual segregation of molecules as a result of elastic properties of single molecules and bonds combined with the properties of the cell membrane. Based on this model a computational algorithm for the Bayesian statistical analysis of fluorescence images is developed in order to estimate relevant physical parameters that cannot be measured explicitly.
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| 关 键 词: |
免疫突触; 荧光标记; 分子的相互隔离; 贝叶斯统计分析的计算算法
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| 课程来源: |
视频讲座网
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| 最后编审: |
2020-06-01：吴雨秋(课程编辑志愿者)
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| 阅读次数: |
42
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