Intercellular membrane protein interactions - identification using protein microarrays and characterisation

细胞间膜蛋白相互作用 - 使用蛋白质微阵列进行鉴定和表征

• 批准号: G0500845/1
• 负责人: A Barclay
• 金额: $ 35.93万
• 依托单位: University of Oxford
• 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=G0500845%2F1
• 关键词: Intercellular; membrane; protein; interactions; identification

Communication between cells is an essential process in biology. For instance one gets very different types of response in terms of strength, duration and extent between a local pathogen infection with a cut and one that affects the whole body such is in influenza. These events are controlled through proteins at the surface of cells. If the response is not optimum then there is a potential for autoimmune disease or the failure to clear cancer cells. Interactions at the surface of these cells are crucial in obtaining the correct control. The same is true in other organs e.g. in brain to ensure the correct arrangement of neurons, and with blood cells to ensure they migrate properly through the blood vessels. The surfaces of these cell types contain hundreds of different proteins. Some of their interactions are known but many are not. This project aims to utilise newly established nanotechnology protein methods to identify and characterise these interactions on a systematic basis. Firstly a subset of proteins that are predicted on structural grounds to be likely to interact with other surface proteins will be selected and small amounts of protein made using recombinant DNA methods. These will be arrayed in a grid of several hundred small spots, with around 200 picogram (one million millionth of a gram) of each protein and tested for binding to possible ligands. The identification of the interactions is a first step in understanding their functions in biology. There is also a potential clinical benefit in that these interactions are possible therapeutic targets where regulation is not optimal, e.g. in enhancing responses against viruses and cancer cells, and in switching off responses in autoimmune diseases. The technology should be applicable to other areas such as in fertilisation namely in sperm egg interactions. I will continue to ensure that the results are published promptly and well detailed on the WWW. Medical benefits are likely to be in the long term but there is considerable interest in the technology and I will continue to ensure this is well publicised e.g. the new microarray technology was highlighted recently on the MRC WWW page (March 2005).

细胞间的通讯是生物学中必不可少的过程。例如，从强度、持续时间和程度来看，局部病原体感染与流感等影响全身的病原体感染之间的反应是非常不同的。这些事件是由细胞表面的蛋白质控制的。如果反应不是最佳的，那么就有潜在的自身免疫性疾病或无法清除癌细胞。这些细胞表面的相互作用对于获得正确的控制至关重要。在其他器官中也是如此，例如在大脑中确保神经元的正确排列，以及与血细胞一起确保它们在血管中正确移动。这些细胞的表面含有数百种不同的蛋白质。它们之间的一些相互作用是已知的，但很多是未知的。该项目旨在利用新建立的纳米技术蛋白质方法在系统的基础上识别和表征这些相互作用。首先，从结构角度预测可能与其他表面蛋白质相互作用的蛋白质子集将被选择，并使用重组DNA方法制造少量蛋白质。这些蛋白质将被排列成一个由几百个小点组成的网格，每种蛋白质大约有200皮克（1克的百万分之一），并被测试与可能的配体的结合。确定相互作用是了解它们在生物学中的功能的第一步。还有一个潜在的临床益处，因为这些相互作用可能是调节不理想的治疗靶点，例如增强对病毒和癌细胞的反应，以及关闭自身免疫性疾病的反应。这项技术应该适用于其他领域，比如受精，即精子和卵子的相互作用。我将继续确保结果及时和详细地公布在WWW上。医疗效益可能是长期的，但对这项技术有相当大的兴趣，我将继续确保这一点得到很好的宣传，例如，MRC WWW页面最近强调了新的微阵列技术（2005年3月）。