Cells to Molecules: Structural EM at Newcastle University

细胞到分子：纽卡斯尔大学的结构电磁学

• 批准号: BB/R013942/1
• 负责人: Martin Noble
• 金额: $ 37.54万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR013942%2F1
• 关键词: Cells; Molecules; Structural; EM; Newcastle

Light microscopes are limited in terms of the level of detail they can provide of cells and it is not possible to use them to look at the fine structure of the internal features of cells or molecules. Transmission Electron Microscopes (TEM) use high energy electrons rather than light to produce images and provide over 1000 times the level of detail possible with a light microscope. Using a TEM it is possible to look at the structures within cells to see how they form and even see the arrangement of atoms within proteins and protein machines. In the last twenty years, the technology behind TEM instruments and the cameras used to acquire images from them have undergone significant developments. One of the major drawbacks of imaging with a TEM is the limited contrast available from biological samples and the resulting impact of noise on the images. This makes our studies difficult as it is often hard to see the structures we are looking at clearly. Modern TEMs are equipped with cameras capable of taking images with very low noise and even capturing movies to allow very fine detail to be observed that would otherwise be lost. One major advance has been the preparation of samples at very low-temperatures, this allows cells and molecules to be viewed in a naturally hydrated state and minimises the spread of sample damage caused by the electrons from the microscope. This technique is known as cryo-EM and permits cells and proteins to be imaged with a level of detail at which it is possible to see the individual amino-acid components of proteins.Our research projects cover a wide range of subjects from understanding how the intestinal pathogen Clostridium difficile forms disinfectant resistant spores; to the production of DNA-based nanowires for use in electronics and conductive polymer materials. Other projects seek to understand how particular genes influence the formation of kidney tissues. We are also interested in how proteins called cyclin dependent kinases interact with their partner proteins to influence cell division and the production of RNA messages encoding proteins. This work has implications for the development of anti-cancer drugs.

光学显微镜在它们可以提供的细胞细节水平方面是有限的，并且不可能使用它们来观察细胞或分子内部特征的精细结构。透射电子显微镜（TEM）使用高能电子而不是光来产生图像，并提供超过1000倍的细节水平与光学显微镜可能。使用TEM可以观察细胞内的结构，以了解它们是如何形成的，甚至可以看到蛋白质和蛋白质机器内原子的排列。在过去的二十年中，TEM仪器背后的技术和用于从它们获取图像的相机经历了重大的发展。TEM成像的主要缺点之一是生物样品的对比度有限，以及由此产生的噪声对图像的影响。这使得我们的研究变得困难，因为我们通常很难清楚地看到我们正在观察的结构。现代TEM配备了能够以非常低的噪声拍摄图像的相机，甚至可以捕获电影，以允许观察到非常精细的细节，否则这些细节会丢失。一个主要的进步是在非常低的温度下制备样品，这使得细胞和分子可以在自然水合状态下观察，并最大限度地减少了由显微镜电子引起的样品损伤的扩散。这种技术被称为cryo-EM，它可以对细胞和蛋白质进行成像，并且可以看到蛋白质的单个氨基酸成分。我们的研究项目涵盖了广泛的主题，从了解肠道病原体艰难梭菌如何形成耐消毒剂的孢子，到生产用于电子和导电聚合物材料的DNA纳米线。其他项目试图了解特定基因如何影响肾组织的形成。我们也对称为细胞周期蛋白依赖性激酶的蛋白质如何与它们的伴侣蛋白质相互作用以影响细胞分裂和编码蛋白质的RNA信息的产生感兴趣。这项工作对抗癌药物的开发具有重要意义。

项目成果

Structural maturation of SYCP1-mediated meiotic chromosome synapsis through conformational remodelling by molecular adapter SYCE3

• DOI: 10.1101/2022.03.06.483192
• 发表时间: 2022-03
• 期刊: bioRxiv
• 作者: James H. Crichton;J. M. Dunce;O. Dunne;L. Salmon;Paul S. Devenney;J. Lawson;I. Adams;O. Davies

Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3.

• DOI: 10.1038/s41594-022-00909-1
• 发表时间: 2023-03
• 期刊: Nature structural & molecular biology
• 影响因子: 16.8
• 作者: Crichton JH;Dunce JM;Dunne OM;Salmon LJ;Devenney PS;Lawson J;Adams IR;Davies OR
• 通讯作者: Davies OR

Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function.

• DOI: 10.1002/sctm.20-0211
• 发表时间: 2020-12
• 期刊: Stem cells translational medicine
• 影响因子: 6
• 作者: Cerniauskas E;Kurzawa-Akanbi M;Xie L;Hallam D;Moya-Molina M;White K;Steel D;Doherty M;Whitfield P;Al-Aama J;Armstrong L;Kavanagh D;Lambris JD;Korolchuk VI;Harris C;Lako M
• 通讯作者: Lako M

Coiled-coil structure of meiosis protein TEX12 and conformational regulation by its C-terminal tip.

• DOI: 10.1038/s42003-022-03886-9
• 发表时间: 2022-09-07
• 期刊: Communications biology
• 影响因子: 5.9

Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly.

• DOI: 10.1038/s41594-018-0078-9
• 发表时间: 2018-07
• 期刊: Nature structural & molecular biology
• 影响因子: 16.8
• 作者: Dunce JM;Dunne OM;Ratcliff M;Millán C;Madgwick S;Usón I;Davies OR
• 通讯作者: Davies OR