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。染色体在细胞核中复制；在细胞分裂过程中，每个细胞的一个拷贝被分配到每个子细胞。错误会导致细胞死亡、出生缺陷和癌症。染色体通过有丝分裂纺锤体分布到子细胞，这是一种仅用于移动染色体的临时结构。首先，复制的染色体在纺锤体的中间排列。纺锤纤维将它们连接到相反的纺锤杆上，类似于一对不同颜色的船在湖中央排成一排，每种颜色的两条船（染色体）通过电缆（纺锤纤维）连接到湖对面的码头（纺锤杆）上。两个码头各有一艘不同颜色的船。我们研究将染色体（船）移动到极点（码头）的力。大多数细胞生物学家认为，船只是通过码头上的绞车或船上的绞车，或两者兼而有之，卷绕到码头上的。我们的实验反驳了这个观点。我们用激光微束切断电缆（纺锤形纤维），船只仍然可以移动到他们的码头。我们认为运动的力来自水流（来自主轴矩阵）。我们从实验中得出了同样的结论，在实验中，电缆被溶解（用一种药物），然后船只迅速移动到一个码头。让船只在没有缆绳的情况下移动，使我们能够识别和研究可能产生力的水（主轴矩阵）成分。我们也研究染色体之间的交流（船）。发令员的哨声响起（一个全球性的发令信号）后，每艘船都向码头移动。人们通常认为，这就是所需要的一切，但我们已经识别出船只之间的信号，这些信号改变了它们对码头的运动。例如，相同颜色的船向相反的码头移动时，它们的速度是协调的：当我们轻微损坏（但不切断）一艘船和它的码头之间的电缆时，这艘船和它的伙伴船（前往另一个码头）都停止移动。在这个例子中，通信代理是“系绳”，我们最近发现的通用纺锤组件，类似于连接相同颜色的船只的蹦极绳。当我们用激光切断一根蹦极绳（系绳），然后轻微损坏缆绳，伙伴船之间的通信停止：船独立移动。在其他交流的例子中，染色体之间没有物理联系。我们研究计划的总体目标是了解力的产生和染色体间的通信系统。我们的短期目标是确定非缆索（非纺锤体纤维）力元素，并表征染色体间协调的系索和其他元素。重要性：通过了解染色体运动是如何发生和被控制的，我们可以更好地理解导致出生缺陷和癌症的染色体分布错误的原因；这样的理解可以导致预防。

I study the basic mechanisms that control chromosome movements during cell division. Chromosomes are duplicated in the nucleus; then one copy of each is distributed to each daughter cell during cell division. Errors can cause cell death, birth defects and cancers.    Chromosomes are distributed to daughter cells by the mitotic spindle, a temporary structure used solely to move chromosomes. First the duplicated chromosomes line up in the middle of the spindle. Spindle fibres connect them to opposite spindle poles, analogous to pairs of differently coloured boats lined up in the middle of a lake with the two boats (chromosomes) of each colour connected by a cable (spindle fibre) to a dock (spindle pole) on opposite sides of the lake. Each of the two docks gets one boat of each colour.     We study the forces that move chromosomes (boats) to their poles (docks). Most cell biologists think that boats are reeled in to their docks by winches at the dock, or winches at the boat, or both. Our experiments dispute this idea. We sever the cables (spindle fibres) with a laser microbeam and the boats still move to their dock. We suggest that the force for movement arises from water currents (from a spindle matrix). We reached the same conclusion from experiments in which the cables were dissolved (with a drug) and the boats then rapidly moved to one dock. Having boats move without cables allows us to identify and study the water (spindle matrix) components that may produce the force.    We also study communication between the chromosomes (boats). Each boat moves to its dock after a starter's whistle sounds (a global start signal). It often is assumed that this is all that is needed, but we have identified signals between boats that alters their motions to their docks. For example, boats of the same colour moving to opposite docks coordinate their speeds: when we weakly damage (but do not sever) the cable between a boat and its dock, both that boat and its partner boat (going to the other dock) stop moving. In this example the communication agents are "tethers", universal spindle components that we recently uncovered, analogous to bungee cords that connect boats of the same colour. When we cut a bungee cord (tether) with a laser, and then weakly damage the cable, communication between partner boats stops: the boats move independently. In other examples of communication there are no physical connections between the chromosomes. The overall goal of our research program is to understand the force production and inter-chromosome communication systems. Our short-term goal is to identify the non-cable (non-spindle fibre) force elements and to characterise the tethers and other elements of inter-chromosome coordination.    Importance: By knowing how chromosome movements occur and are controlled we can better understand the causes of errors in chromosome distributions that cause birth defects and cancers; such understanding can lead to preventions.