权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Integrin specificity regulating chemotaxis in 3-dimensional matrix.

整合素特异性调节 3 维基质中的趋化性。

基本信息

批准号：
BB/D016185/1
负责人：
Madeline Parsons
金额：
$ 37.05万
依托单位：
King's College London
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%2FD016185%2F1
关键词：
Integrin specificity regulating chemotaxis dimensional

项目摘要

The movement of different types of cell within the body is vital for normal embryo development, immunity and wound healing in mammals. It is vital that the way in which cells move or 'migrate' and the proteins involved in this process are fully understood in order to allow the design of therapies to tackle diseases where cell movement is uncontrolled. Cell migration in humans is not a random process, but a highly complex, tightly regulated one. Initially, the cell must receive a signal from the environment to use as a cue to migrate. This provides the cell with a sense of direction and stimulates movement persistently in one direction, namely towards the source of the signal. For example, during wound healing, soluble factors are released into the wound itself by blood cells or invading bacteria. These factors trigger cells at the edge of the wound to move in and repopulate the wound space, and begin the healing process. The actual mechanism that cells use to co-ordinate these events is still not well understood. However, what is known is that cells must first attach to the surrounding tissue proteins, such as collagen, to be able to move. Attachment is achieved mainly using specialized membrane-bound (receptor) proteins called integrins. Integrins anchor the cells to the surrounding matrix and, in doing so, trigger changes to specific proteins inside the cell. A key early component of cell attachment is a protein called actin, which forms long structural polymers to give the cell a rigid shape. These actin polymers, known as the cytoskeleton, provide a crucial mechanical scaffold for the cell to use to propel itself forward. However, in order to allow the cell to move efficiently, the cytoskeleton is constantly being remodeled and reformed. This process is controlled initially from the cell membrane by integrins, although the way in which the cell does this is not well understood. The study outlined here aims to use a number of ways of imaging combined with biochemical analysis to characterise the role of integrins and associated proteins in cell migration in isolated human cells. It is important to understand exactly how and where in the cell the integrin is being controlled by binding proteins, and how this can alter the cell's response to external stimuli. It is possible to directly track the behaviour of these proteins in living cells. The protein of interest is tagged with a fluorescent dye, meaning it can be seen if excited by light of a specific colour. These molecules are then delivered into living cells. The protein can be seen using a highly sensitive camera attached to a microscope. By watching cells whilst they are moving using microscopy, and following protein movement inside the cells, we can work out the importance of these proteins in cell motility. This is a very exciting and important scientific field which allows us to study the fundamental questions of how human cells move and ultimately how they change to become, for example, cancer cells. This information has very important implications for developing new therapies to treat diseases. Once we understand the way in which a cell uses the integrins to move, we can begin to manipulate these proteins with a view to developing treatments to prevent disorders such as cancer, inflammatory asthma and developmental abnormalities.

哺乳动物体内不同类型细胞的运动对正常胚胎发育、免疫和伤口愈合至关重要。细胞移动或“迁移”的方式以及参与这一过程的蛋白质是至关重要的，以便设计治疗方法来治疗细胞运动不受控制的疾病。人类的细胞迁移不是一个随机的过程，而是一个高度复杂、受到严格调控的过程。最初，细胞必须接收到来自环境的信号，作为迁移的线索。这为细胞提供了方向感，并刺激细胞在一个方向上持续运动，即朝着信号源运动。例如，在伤口愈合过程中，可溶性因子被血细胞或入侵细菌释放到伤口本身。这些因素触发伤口边缘的细胞进入并重新填充伤口空间，并开始愈合过程。细胞用来协调这些事件的实际机制仍然没有被很好地理解。然而，我们所知道的是，细胞必须首先附着在周围的组织蛋白上，如胶原蛋白，才能移动。附着主要是通过称为整合素的特殊膜结合（受体）蛋白来实现的。整合素将细胞固定在周围的基质上，并在此过程中触发细胞内特定蛋白质的变化。细胞附着的早期关键成分是一种叫做肌动蛋白的蛋白质，它形成长结构聚合物，使细胞具有刚性形状。这些肌动蛋白聚合物，被称为细胞骨架，为细胞提供了一个关键的机械支架，用来推动细胞前进。然而，为了使细胞有效地移动，细胞骨架不断地被重塑和改造。这一过程最初是由细胞膜上的整合素控制的，尽管细胞是如何做到这一点的还不是很清楚。这里概述的研究旨在使用多种成像方法结合生化分析来表征整合素和相关蛋白在分离的人类细胞中细胞迁移中的作用。重要的是要准确地了解细胞中整合素是如何以及在哪里被结合蛋白控制的，以及这是如何改变细胞对外部刺激的反应的。在活细胞中直接追踪这些蛋白质的行为是可能的。感兴趣的蛋白质被荧光染料标记，这意味着如果被特定颜色的光激发，就可以看到它。然后这些分子被输送到活细胞中。这种蛋白质可以用连接在显微镜上的高灵敏度相机观察到。通过使用显微镜观察细胞的运动，并跟踪细胞内蛋白质的运动，我们可以计算出这些蛋白质在细胞运动中的重要性。这是一个非常令人兴奋和重要的科学领域，它使我们能够研究人类细胞是如何运动的基本问题，以及它们最终是如何变成癌细胞的。这一信息对开发治疗疾病的新疗法具有非常重要的意义。一旦我们了解了细胞使用整合素移动的方式，我们就可以开始操纵这些蛋白质，以期开发出预防癌症、炎症性哮喘和发育异常等疾病的治疗方法。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.

DOI：
10.1083/jcb.200912014
发表时间：
2010-04-19
期刊：
The Journal of cell biology
影响因子：
0
作者：
Worth DC;Hodivala-Dilke K;Robinson SD;King SJ;Morton PE;Gertler FB;Humphries MJ;Parsons M
通讯作者：
Parsons M

Live cell imaging analysis of receptor function.

受体功能的活细胞成像分析。