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Mechanisms mediating intracellular sorting of Roundabout

介导 Roundabout 细胞内排序的机制

基本信息

批准号：
BB/G022399/1
负责人：
Guy Justin Clive Tear
金额：
$ 44.19万
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：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG022399%2F1
关键词：
Mechanisms mediating intracellular sorting Roundabout

项目摘要

We are dependent on our nervous system functioning correctly for us to move, think, learn, speak and control our bodies. To do this all our nerve cells must connect up in the brain and to the parts of the body they control. Most of this 'wiring together' happens during the growth and development of the embryo in pregnancy. To do this each nerve cell must extend a long process, called an axon, over large distances and through complex environments to find and connect to its appropriate partners. Each axon is guided when to turn and which way to grow to reach its partner by sensing specific chemicals or molecular 'cues' in different parts of the body. These signals are detected by 'receptor' proteins at the tip of the growing axon. The activity of these receptors change as the axons grow into different regions, We want to find the molecules that work to control the activity of these receptors as they guide axons along their pathways. We know already that many of the same molecules and receptors in mammals are also present in smaller animals like the fruitfly Drosophila where they do the same job but on a simpler scale. We are using Drosophila to characterise how one of these receptors called Roundabout is regulated in a subset of neurons. We know that Roundabout must be precisely regulated for axons to grow correctly. Although we have identied one key regulator of the Roundabout protein, a protein called Commissureless we do not know precisely how this molecule acts to regulate Roundabout. We plan to use Drosophila as a model system where we can watch exactly how the Roundabout and Commissureless molecules behave in the axons as they grow. This will give us information on the dynamics of the process. We also use Drosophila as a model system to rapidly identify and test the role of further molecules that may act in this process, e.g. those that bind to Commissureless. By using Drosophila we can reduce the need to sacrifice large numbers of mice in research. Once we have found out how these molecules work in Drosophila we will inform other researchers so that the molecules can be tested in other model systems. We need this information both to learn how the nervous system is made and to find out what molecules might be useful in helping us to repair neural injuries or diseases that lead to paralysis or neural degeneration. Unfortunately mammals cannot repair nerve damage that occurs in the brain, our hope is that by identifying the molecules that were originally used to drive and direct nerve cell growth in the embryo we can re-supply these molecules to help nerve cell regeneration in people.

我们依赖于我们的神经系统正常运作，让我们移动，思考，学习，说话和控制我们的身体。要做到这一点，我们所有的神经细胞都必须连接到大脑和它们控制的身体部位。大多数这种“连接在一起”发生在怀孕期间胚胎的生长和发育过程中。要做到这一点，每个神经细胞必须延伸一个很长的过程，称为轴突，在很长的距离和复杂的环境中找到并连接到合适的伙伴。每个轴突通过感知身体不同部位的特定化学物质或分子“线索”来指导何时转向以及以何种方式生长以到达其伴侣。这些信号被生长轴突顶端的“受体”蛋白检测到。这些受体的活性随着轴突生长到不同的区域而改变，我们想找到那些分子，它们在引导轴突沿着它们的通路时，控制这些受体的活性.我们已经知道，哺乳动物中的许多相同分子和受体也存在于较小的动物中，如果蝇，它们在那里做同样的工作，但规模更简单。我们正在用果蝇来研究这些受体中的一种叫做Roundabout的受体是如何在神经元的一个子集中被调节的。我们知道Roundabout必须被精确地调节才能使轴突正确地生长。虽然我们已经确定了Roundabout蛋白的一个关键调节因子，一种称为Commissuerless的蛋白质，但我们并不确切知道这种分子如何调节Roundabout。我们计划使用果蝇作为模型系统，在那里我们可以确切地观察Roundabout和Commissuerless分子在轴突生长时的行为。这将为我们提供有关该过程动态的信息。我们还使用果蝇作为模型系统，以快速识别和测试可能在此过程中起作用的其他分子的作用，例如，那些与Commissueless结合的分子。通过使用果蝇，我们可以减少在研究中牺牲大量小鼠的需要。一旦我们发现这些分子如何在果蝇中起作用，我们将通知其他研究人员，以便这些分子可以在其他模型系统中进行测试。我们需要这些信息来了解神经系统是如何形成的，并找出哪些分子可能有助于我们修复导致瘫痪或神经退化的神经损伤或疾病。不幸的是，哺乳动物无法修复大脑中发生的神经损伤，我们希望通过识别最初用于驱动和指导胚胎神经细胞生长的分子，我们可以重新供应这些分子，以帮助人类神经细胞再生。