Mechanisms of chromosome movement during cell division

我研究细胞分裂过程中控制染色体运动的基本机制。在细胞分裂之前，每条染色体都是复制的；我研究了两个子细胞是如何接收到每个染色体的一个拷贝的。这一点很重要，因为染色体携带遗传信息，而遗传物质分布中的错误会导致细胞死亡、出生缺陷和癌症。我们的一些工作涉及将染色体移动到两个新细胞的力量。在具有成对重复染色体的细胞中，由于配对染色体排列在细胞的中间，纺锤体纤维将配对染色体连接到相反的两极，从而产生了适当的染色体分布。伴侣们同时分开，移动到相反的极点；每条纺锤体纤维随着染色体的移动而缩短。这类似于一对不同颜色的船在湖中央排成一排。每种颜色的2艘船通过电缆连接到湖对面的码头，因此每个码头有一艘每种颜色的船。大多数细胞生物学家认为，船（染色体）是通过码头上的绞车或船上的绞车，或两者兼而有之的作用，被卷绕到码头（极点）上的。我的实验反驳了这个想法：我们用激光或紫外线微束照射切断了电缆（纺锤形纤维），船只仍然可以移动到它们的码头。我们认为，运动的力来自于水流（来自于主轴矩阵），缆绳不会拉动船，而是引导船到码头。因为缆索（纺锤微管）不能弯曲，所以它们能抵抗船只的运动，所以船只向码头移动的速度是由缆索卷绕的速度决定的。我们提出的实验研究纺锤体基质如何产生力，以及其他蛋白质如何参与其中。例如，我们会用一种叫做紫杉醇的药物稳定缆绳，使绞车不工作，然后切断缆绳。如果电流产生了移动船只的力量，正如我们所相信的那样，当电缆障碍物被移除时，船只应该向码头移动。我们提出的实验旨在了解染色体移动的基本机制。我们还研究了一个不太为人所知的问题，即船只之间的通信。发令员的哨声响起（一个全球性的发令信号）后，每艘船就会移到码头上，人们通常认为这就是所需要的一切。但我们已经确定了船只之间的各种本地信号可以改变它们对码头的运动。例如，在较弱的微束辐射破坏了绿色船和它的码头之间的电缆后，这艘船和它的伙伴绿色船（前往另一个码头）都停止了移动：伙伴船进行通信。在这个特殊的例子中，我们对机理有了一些了解。当同一颜色的船向相反的极点移动时，用蹦极绳连接（在细胞中它们被称为“系绳”），通过切断船的尾部（染色体的尾部）来识别。当船被切断的部分被收缩的蹦极绳拉向伙伴船时，船继续移动。我们建议（用激光）切断一艘船的蹦极绳，然后破坏相关的电缆：如果合作伙伴通过蹦极绳进行通信，当我们切断蹦极绳时，通信应该停止，这样被损坏的电缆的船会停止移动，而它的伙伴不会。在“交流”的其他例子中，我们不理解协调运动是如何产生的。我们的实验旨在更好地理解这些通信系统。通过理解它们，我们可以更好地理解错误是如何产生的，以及如何改进它们。

I study the basic mechanisms that control chromosome movements during cell division. Prior to cell division, each chromosome is duplicated; I study how each of the two daughter cells receives one copy of each chromosome. This is important because chromosomes carry genetic information and errors in the distribution of genetic material can cause cell death, birth defects and cancers. Some of our work deals with the forces that move the chromosomes to the two new cells. In cells with pairs of duplicated chromosomes, proper chromosome distribution arises because partner chromosomes line up in the middle of the cell and spindle fibres connect partners to opposite poles. The partners separate simultaneously and move to opposite poles; each spindle fibre shortens as its chromosome moves. This is analogous to pairs of differently coloured boats lined up in the middle of a lake. The 2 boats of each colour are connected by cables to docks on opposite sides of the lake so each dock gets one boat of each colour. Most cell biologists think that boats (chromosomes) are reeled to their docks (poles) by the action of winches at the dock, or winches at the boat, or both. My experiments dispute this idea: we severed the cable (the spindle fibre) with laser or ultraviolet light microbeam irradiations and the boats still moved to their dock. We suggest that the force for movement arises from water currents (from a spindle matrix) and that the cable does not pull the boat but rather guides the boat to the dock. Because the cables (spindle microtubules) resist bending, they resist the movements of the boats, so the speed that a boat moves to its dock is governed by the speed of reeling in the cable. Our proposed experiments study how the spindle matrix produces the force, and how other proteins might be involved. For example, we will stabilise the cables so the winches don’t work (using a drug called paclitaxel) and then sever a cable. If the current produces the force to move the boats, as we believe, the boat should move toward the dock when the cable impediment is removed. Our proposed experiments aim to understand the basic mechanisms that move chromosomes. We also study a less-well understood issue, communication between the boats. Each boat moves to its dock after a starter’s whistle is sounded (a global start signal), and it often is assumed that that is all that is needed. But we have identified various local signals between boats that can alter their motion to their dock. For example, after weaker microbeam irradiation damages the cable between a green boat and its dock, both that boat and its partner green boat (going to the other dock) stop moving: partner boats communicate. In this particular example we have some idea of the mechanism. Boats of the same colour when moving to opposite poles are connected by bungee cords (in cells they are called ‘tethers’), identified by cutting the trailing part of the boat (a trailing arm of the chromosome). The boats keep moving as the severed part of the boat is pulled to the partner boat by the contracting bungee cord. We propose to cut a bungee cord of a boat (with a laser) and then damage the associated cable: if the partners communicate via the bungee cord, communication should stop when we cut a bungee cord so the boat with damaged cable will stop moving but its partner will not. In the other examples of ‘communication’ we do not understand how the coordinated movements arise. Our experiments aim to better understand these communication systems. By understanding them we can better understand how errors arise and how one might ameliorate them.