Super resolution imaging of protein dynamics and functions in physiology and disease

生理学和疾病中蛋白质动力学和功能的超分辨率成像

• 批准号: MR/K015613/1
• 负责人: Michelle Peckham
• 金额: $ 155.14万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015613%2F1
• 关键词: Super; resolution; imaging; protein; dynamics

A major challenge in biomedical research is to be able to see inside a cell with enough detail to be able to understand how proteins interact with each other, and what goes wrong in disease. Typically, to see where a protein is inside a cell, a researcher will use a microscope that illuminates the cells with visible light together with dyes to label the proteins. This type of microscope can see detail to about 200nm (1/5000th of a millimetre), but cellular organelles are commonly at least 4 fold smaller than this, and proteins at least 10 fold smaller. Imaging these organelles and proteins with a normal light microscope does not reveal enough detail about the organisation of proteins and organelles within a cell, or help us understand the normal cellular functions of the proteins, and how they are affected by disease. To overcome this problem, several new types of microscopy have been recently invented to help see the detailed organisation of proteins inside cells. The goal of our research is to build a new microscope and develop new dyes that will help us achieve this, and solve important biomedical questions that are impossible to solve with our existing microscopes.

生物医学研究的一个主要挑战是能够看到细胞内部的足够细节，以便能够了解蛋白质如何相互作用，以及疾病中出现了什么问题。通常情况下，为了查看蛋白质在细胞内的位置，研究人员将使用显微镜，用可见光照射细胞，并用染料标记蛋白质。这种类型的显微镜可以看到大约200纳米（1/5000毫米）的细节，但细胞器通常比这个小至少4倍，蛋白质至少小10倍。用普通光学显微镜对这些细胞器和蛋白质进行成像，并不能揭示细胞内蛋白质和细胞器组织的足够细节，也不能帮助我们了解蛋白质的正常细胞功能以及它们如何受到疾病的影响。为了克服这个问题，最近发明了几种新型显微镜，以帮助观察细胞内蛋白质的详细组织。我们研究的目标是建立一个新的显微镜和开发新的染料，这将有助于我们实现这一目标，并解决重要的生物医学问题，是不可能解决与我们现有的显微镜。

项目成果

Nanoscale Pattern Extraction from Relative Positions of Sparse 3D Localizations.

• DOI: 10.1021/acs.nanolett.0c03332
• 发表时间: 2021-02-10
• 期刊: Nano letters
• 影响因子: 10.8
• 作者: Curd AP;Leng J;Hughes RE;Cleasby AJ;Rogers B;Trinh CH;Baird MA;Takagi Y;Tiede C;Sieben C;Manley S;Schlichthaerle T;Jungmann R;Ries J;Shroff H;Peckham M
• 通讯作者: Peckham M

Affimers and nanobodies as molecular probes and their applications in imaging.

• DOI: 10.1242/jcs.259168
• 发表时间: 2022-07-15
• 期刊: Journal of cell science
• 影响因子: 4

Visualisation and analysis of hepatitis C virus non-structural proteins using super-resolution microscopy.

• DOI: 10.1038/s41598-018-31861-0
• 发表时间: 2018-09-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bartlett C;Curd A;Peckham M;Harris M
• 通讯作者: Harris M

Nanoscale pattern extraction from relative positions of sparse 3D localisations

从稀疏 3D 定位的相对位置提取纳米级图案

• DOI: 10.1101/2020.02.13.947135
• 发表时间: 2020
• 作者: Curd A

Construction of an instant structured illumination microscope.

• DOI: 10.1016/j.ymeth.2015.07.012
• 发表时间: 2015-10-15
• 期刊: Methods (San Diego, Calif.)
• 作者: Curd A;Cleasby A;Makowska K;York A;Shroff H;Peckham M
• 通讯作者: Peckham M