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发表于 2011-6-7 12:49 |只看该作者 |倒序浏览 |打印
本帖最后由 StephenW 于 2011-6-7 12:50 编辑

http://www.sciencealert.com.au/news/20110606-22242.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencealert-latestnews+%28ScienceAlert-Latest+Stories%29
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Supermicroscope pins immune ‘switch’                        
The University of New South Wales                                          
Tuesday, 07 June 2011        

T cells are the 'front-line' troops that alert our immune system to go on the defensive against invaders.
Image: Henrik5000/iStockphoto


Using the only microscope of its kind in Australia, medical scientists have been able for the first time to see the inner workings of T-cells, the front-line troops that alert our immune system to go on the defensive against germs and other invaders in our bloodstream.

The discovery overturns prevailing understanding, identifying the exact molecular 'switch' that spurs T-cells into action -- a breakthrough that could lead to treatments for a range of conditions from auto-immune diseases to cancer.

The findings, by researchers at the University of New South Wales (UNSW), are reported in the journal Nature Immunology.

Studying a cell protein important in early immune response, the researchers led by Associate Professor Katharina Gaus from UNSW's Centre for Vascular Research at the Lowy Cancer Research Centre, used Australia's only microscope capable of super-resolution fluorescence microscopy to image the protein molecule-by-molecule to reveal the immunity 'switch'.

The technology is a major breakthrough for science, Dr Gaus said. Currently there are only half a dozen of the 'super' microscopes in use around the world.

"Previously you could see T-cells under a microscope but you couldn't see what their individual molecules were doing," Dr Gaus said.

Using the new microscope the scientists were able to image molecules as small as 10 nanometres. Dr Gaus said that what the team found overturns the existing understanding of T-cell activation.

"Previously it was thought that T-cell signalling was initiated at the cell surface in molecular clusters that formed around the activated receptor.

"In fact, what happens is that small membrane-enclosed sacks called vesicles inside the cell travel to the receptor, pick up the signal and then leave again," she said.

Dr Gaus said the discovery explained how the immune response could occur so quickly.

"There is this rolling amplification. The signalling station is like a docking port or an airport with vesicles like planes landing and taking off. The process allows a few receptors to activate a cell and then trigger the entire immune response," she said.

PhD candidate David Williamson, whose research formed the basis of the paper, said the discovery showed what could be achieved with the new generation of super-resolution fluorescence microscopes.

"In conventional microscopy, all the target molecules are lit up at once and individual molecules become lost amongst their neighbours -- it's like trying to follow a conversation in a crowd where everyone is talking at once.

"With our microscope we can make the target molecules light up one at a time and precisely determine their location while their neighbours remain dark. This 'role call' of all the target molecules means we can then build a 'super resolution' image of the sample," he said.

The next step was to pinpoint other key proteins to get a complete picture of T-cell activity and to extend the microscope to capture 3-D images with the same unprecedented resolution.

"Being able to see the behaviour and function of individual molecules in a live cell is the equivalent of seeing atoms for the first time. It could change the whole concept of molecular and cell biology," Mr Williamson said.

Other research team members were physicist Dr Dylan Owen, cell biologists Dr Jérémie Rossy and Dr Astrid Magenau, from the Centre for Vascular Research, and Professor Justin Gooding and Matthias Wehrmann, from UNSW's School of Chemistry and the Australian Centre for Nanomedicine. The research was supported by funding from the National Health and Medical Research Council, Australian Research Council and Human Frontier Science Program.

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发表于 2011-6-7 12:52 |只看该作者
使用其在澳大利亚独一无二的显微镜,医学科学家们一直在为第一次看到的T -细胞,一线部队的内部工作方式的提醒我们的免疫系统去对抗入侵的细菌和其他防御能力我们的血液。

这一发现推翻了当时的认识,确定确切的分子'开关'的马刺队为行动的T细胞 - 一种突破,它可能会导致对于从自身免疫疾病的治疗癌症的条件范围。

该研究由新南威尔士大学(UNSW)的研究人员的调查结果,公布在自然免疫学杂志。

研究一种细胞蛋白的早期免疫反应的重要的带动下,副教授卡塔琳娜Gaus血管研究的新南威尔士大学的中心在洛伊癌症研究中心的研究人员,利用澳大利亚唯一的显微镜,超分辨荧光能显微图像的蛋白质分子分揭示免疫分子'开关'。

该技术是科学的一个重大突破,博士Gaus说。目前,只有一半的'超级'显微​​镜打在全世界使用。

“以前,你可以在显微镜下看到的T -细胞,但你无法了解他们的个别分子在做什么,”博士Gaus说。

使用新的显微镜,科学家能够对图像的分子小到10纳米。 Gaus博士说,该研究小组发现什么颠覆了T细胞活化现有的认识。

“以前人们认为的T细胞信号是在细胞表面的分子团簇,围绕激活受体形成发起的。

“其实,什么情况是,小膜封闭包装袋称为细胞内囊泡受体旅行,拿起信号,然后离开了,”她说。

医生说,这一发现解释Gaus如何可能发生的免疫反应这么快。

“有这样滚动放大。信令站像一个对接端口或具有类似飞机降落和起飞的机场是泡。过程允许少数受体激活细胞,然后触发整个免疫反应,”她说。

大卫威廉姆森博士候选人,其研究成果是在文件的基础上指出,此次发现表明什么可与超高分辨率荧光显微镜新一代的实现。

“在传统的显微镜,所有的目标分子立刻亮了起来单个分子成为他们的邻居之间的迷惘 - 它就像试图走一条在人群中每个人的谈话是一次谈话的。

“随着我们的显微镜,我们可以在一时间注册一个目标分子的光,精确地确定其位置,而他们的邻居保持黑暗。这种角色称为'分子的所有目标意味着我们可以建立一个'超分辨率的图像样,“他说。

接下来的步骤是针对其他获得关键蛋白质的T细胞活性的全貌,并扩大显微镜捕捉前所未有的决议具有相同的三维图像。

“能够看到的行为和活细胞中单个分子的功能是首次看到原子等价的。它会改变分子和细胞生物学的整体概念,”威廉姆森说。

其他研究小组成员迪伦博士欧文物理学家,细胞生物学家和医生热雷米罗西博士阿斯特丽德Magenau,从血管研究中心教授和贾斯汀古丁和马提亚Wehrmann,来自新南威尔士大学的化学学院和澳大利亚奈米中心。该研究得到了来自国家健康与医学研究理事会,澳大利亚研究理事会和人类前沿科学计划的资金。

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发表于 2011-6-7 17:13 |只看该作者
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这个显微镜我有研究过,superresolution。
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发表于 2011-6-7 17:36 |只看该作者
本帖最后由 StephenW 于 2011-6-7 17:37 编辑
lifevendor 发表于 2011-6-7 17:13
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这个显微镜我有研究过,superresolution。

University of New South Wales (UNSW) 是我去的大学,但那时显微镜,我只能看到变形虫(amoeba)
目前,只有一半打(half a dozen, i.e. 6)的'超级'显微​​镜在全世界使用.你是幸运的
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