威尼斯注册登录主页的影响

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Pioneering work by researchers from the School of Biological Sciences reveals how invisible triggers orchestrate the earliest-known stages of a key life process, and may help offer clues to improving ways of treating diseases such as cancer.

Transparent cells with nucleus, cell membrane and visible chromosomes

由Corin坎贝尔, 公关和媒体经理,传播和市场营销

As part of the processes of renewal and repair that keep our bodies ticking over, new cells are made in their millions inside each of us every day through cell division.

Despite being one of the most fundamental processes in the biological world, the inner workings of its earliest-known stages have remained shrouded in mystery.

A team led by Professor Bill Earnshaw and Dr Georg Kustatscher have used pioneering techniques to shed light on the first steps taken inside cells as they begin to divide.

“Our study offers a glimpse into the never-before-seen first stages of cell division,恩肖教授说. “It’s a process that’s essential for all plant and animal life on Earth, 但威尼斯注册登录主页它,威尼斯注册登录主页还有很多不完全了解的地方, 尤其是一开始发生的事情.”

All of people’s genetic information is arranged into 23 chromosomes inside their cells. As well as DNA, chromosomes also contain protein molecules – lots of them. 在不分裂的细胞中, the proteins move dynamically on and off DNA to perform and regulate a whole host of functions, from controlling which genes are turned on or off to repairing damaged sections of DNA. The role that many of these proteins play in the first stages of cell division is less clear.

Scientist viewing a DNA autoradiogram showing the results from samples on the lab bench

当细胞分裂时, its chromosomes need to be carefully packaged into compact parcels to ensure they are split equally between the two new cells that are created. Each chromosome is first replicated before the division process starts. Only when replication is complete does what resembles a spaghetti-like jumble of threads compacts into rigid, 位于细胞中心的x形棒. 当细胞开始分裂成两半, a scaffolding of tube-like structures allows molecular motors to drag a copy of each of the 23 chromosomes into the two newly forming cells.

但这并不总是一帆风顺的, as Kustatscher explains: “When millions upon millions of cells are dividing, 有些错误是不可避免的. Errors can lead to new cells that have too many or too few chromosomes, 一种被称为非整倍体的特征. 当它发生在胚胎细胞中时,非整倍体通常是致命的, 但它也是癌症肿瘤的常见特征.”

A better understanding of precisely how chromosomes are packaged and moved into new cells – and the role that proteins play in this – could offer important insights into what may be a key feature of a number of diseases, 恩萧说.

为了进一步研究这个问题, Earnshaw devised a method that would enable them to shed light on the very first stages of cell division.

研究细胞分裂的一个巨大挑战是, 在任何时候, cells in a lab petri dish will be at various stages of the division process. 这 makes it very difficult to analyse what is happening at specific points in the process.

恩肖的方法是由他的日本同事. 久美子Samejima, involves genetically engineering chicken cells – which undergo a very similar division process to people – so that the start of cell division can be blocked using a drug. As soon as the drug is removed, cells begin dividing in a rapid and perfectly synchronised way.

戴着紫色手套的手使用质谱仪.

这 allowed the researchers to use a powerful analytical machine, 叫做质谱仪, to detect which proteins were bound to chromosomes at the very start of cell division, 以及这一过程的前25分钟是如何变化的.

他们跟踪2,500 of these proteins and found that hundreds drop off chromosomes because their functions are not needed during cell division. 与此同时, 其他的蛋白质穿过细胞并附着在染色体上, 当它们准备被拉开进入新形成的细胞时.

“What our results show is that by the time you can see under a microscope that the process of packaging chromosomes has begun there have already been thousands of changes in the proteins that attach to them,恩肖教授说.

染色体,电脑绘图.

The team has developed an app to help researchers studying the proteins they have identified and gain new insights into their involvement in cell division. 这, 反过来, may reveal more key details about the precise mechanisms behind the earliest stages of the process.

The hope is that it could open up a new frontier of research on cell division, and ultimately help facilitate the development of new therapies for diseases characterised by errors in the process, 恩萧说. “这是一个如此基本的过程, cell division is implicated in a wide range of medical disorders in one way or another. By developing a resource for other scientists to use and build upon, we hope our work can act as a focal point for researchers around the world to collaborate to further unpick cell division’s inner workings.”

Their research, which is published in the journal Molecular Cell, was funded by Wellcome. 该论文的开放获取版本是可用的.

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