Mesolab: A Centre for Optical Mesoscopy for Biomedical Research at the University of Strathclyde

Mesolab：斯特拉斯克莱德大学生物医学研究光学介观中心

• 批准号: MR/K015583/1
• 负责人: Gail McConnell
• 金额: $ 196.5万
• 依托单位: University of Strathclyde
• 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%2FK015583%2F1
• 关键词: Mesolab; Centre; Optical; Mesoscopy; Biomedical

During the last twenty years, several different microscopes have been invented which can sharpen the eyes of biomedical scientists, showing more detail in an ever-tinier field of view. Our microscope, developed only recently in the UK, represents lateral thinking: we have broadened the field of view enormously, while keeping the acuity of a conventional microscope. This innovation allows a hundred-fold increase in the volume of the specimen from which sub-cellular detail can be obtained. Individual cells are seen in detail, but so also, for the first time, is their three-dimensional relationship to the whole organ or body. The first confocal results of our optical 'mesoscope' were obtained in the last six months and announced in the 2012 Royal Society Leeuwenhoek Lecture and in a profile in the journal Science. There is now strong worldwide interest because the benefit is obvious in the images already published. There are many applications: here we will describe one of the most important as an example. One image (shown in the Case for Support) shows a median optical section of an entire mouse embryo five millimetres long. This is the first ever confocal image of such a large and thick specimen, with sub-cellular detail including individual Golgi bodies in the same image. The participants in this proposal include the two top UK labs in the field of mouse genetics, where researchers are eagerly seeking to use such images for phenotypic screening of human genes in mouse embryos, one of the most important and large-scale activities in modern biomedicine. We propose to also include in our project equally important but quite different areas of biomedical research where it is almost certain that the optical mesoscope will change the way that work is done. This proposal to the MRC is to set up a centre, the Mesolab, and purchase two optical mesoscope systems at cost from the fledgling manufacturing company Mesolens Ltd (with which we have already worked successfully using our expertise in optical physics and software development to build the prototype confocal system). We are currently pursuing this work with modest but vital EPSRC Knowledge Transfer Agreement funding and support from the University of Strathclyde, as well as a single prototype Mesolens originally developed in the MRC Laboratory of Molecular Biology, Cambridge. We will use the proposed MRC Mesolab facility to develop multi-photon scanning, high-resolution and fast camera imaging, and other imaging modes for the optical mesoscopes, with strong support in manpower, expertise and infrastructure from the University of Strathclyde and substantial input of material support and expertise and intensive design participation by the company, who will be our Project Partner. This development work will be completed within the first three years of the project, but even during this phase biomedical work will occur and there will be synergy between the collaborating biomedical users of the systems and the designers. This engagement (which the large microscope manufacturers have hitherto failed to achieve) will be a key feature of our project. In the second phase, the work will consist exclusively of optimisation of experimental procedures in each application to yield the greatest biomedical benefit. We expect optical mesoscopy to be similar to the original development of the beam-scanning confocal microscope by the MRC, in providing a transforming technology for biomedical research. The creation of the Mesolab will allow scientists rapid access to this next generation microscopy method, which they are already seeking.

在过去的二十年里，几种不同的显微镜已经发明出来，它们可以使生物医学科学家的眼睛变得敏锐，在更小的视野中显示更多的细节。我们的显微镜，最近才在英国开发出来，代表了横向思维：我们极大地拓宽了视野，同时保持了传统显微镜的敏锐度。这一创新允许一百倍增加的样本的体积，从亚细胞的细节可以获得。单个细胞被详细地观察到，但它们与整个器官或身体的三维关系也是第一次。 我们的光学“介观镜”的第一个共焦结果是在过去的六个月里获得的，并在2012年皇家学会列文虎克讲座和《科学》杂志上的一篇简介中宣布。现在全世界都有强烈的兴趣，因为已经公布的图像中的好处是显而易见的。有许多应用程序：在这里，我们将描述一个最重要的作为一个例子。其中一张图片（如支持案例所示）显示了一个5毫米长的整个小鼠胚胎的中间光学切片。这是有史以来第一张如此大而厚的标本的共聚焦图像，在同一张图像中，亚细胞细节包括单个高尔基体。该提案的参与者包括两个英国小鼠遗传学领域的顶级实验室，研究人员正在急切地寻求使用这些图像对小鼠胚胎中的人类基因进行表型筛选，这是现代生物医学中最重要和最大规模的活动之一。我们建议在我们的项目中也包括同样重要但完全不同的生物医学研究领域，几乎可以肯定的是，光学显微镜将改变工作的方式。 向MRC提出的这一建议是建立一个中心，Mesolab，并以成本价从新兴的制造公司Mesolens Ltd购买两个光学介观系统（我们已经成功地利用我们在光学物理和软件开发方面的专业知识建立了原型共聚焦系统）。我们目前正在进行这项工作，来自斯特拉斯克莱德大学的适度但重要的EPSRC知识转移协议资金和支持，以及最初在剑桥MRC分子生物学实验室开发的单一原型Mesolens。 我们将利用拟议的MRC Mesolab设施开发多光子扫描，高分辨率和快速相机成像以及光学介观镜的其他成像模式，斯特拉斯克莱德大学在人力，专业知识和基础设施方面提供强有力的支持，以及大量的材料支持和专业知识的投入以及公司的密集设计参与，他们将成为我们的项目合作伙伴。这项开发工作将在项目的头三年内完成，但即使在这一阶段，生物医学工作也将发生，系统的生物医学用户和设计者之间将产生协同作用。这种参与（大型显微镜制造商迄今未能实现）将是我们项目的一个关键特征。在第二阶段，工作将专门包括优化每个应用中的实验程序，以产生最大的生物医学效益。我们希望光学介观镜类似于MRC最初开发的光束扫描共聚焦显微镜，为生物医学研究提供一种转换技术。Mesolab的创建将使科学家能够快速获得他们已经在寻找的下一代显微镜方法。

项目成果

A new giant lens for confocal mesoscopy

用于共焦介观镜的新型巨型透镜

• 发表时间: 2014
• 作者: Amos W

Intra-colony channel morphology in Escherichia coli biofilms is governed by nutrient availability and substrate stiffness.

• DOI: 10.1016/j.bioflm.2022.100084
• 发表时间: 2022-12
• 期刊: Biofilm
• 影响因子: 6.8

Time-lapse mesoscopy of Candida albicans and Staphylococcus aureus dual-species biofilms reveals a structural role for the hyphae of C. albicans in biofilm formation

• DOI: 10.1101/2023.08.31.555792
• 发表时间: 2023-09
• 期刊: Microbiology
• 影响因子: 1.5
• 作者: K. Baxter;Fiona A. Sargison;J. R. Fitzgerald;Gail McConnell;P. Hoskisson

Light-sheet mesoscopy with the Mesolens provides fast sub-cellular resolution imaging throughout large tissue volumes.

• DOI: 10.1016/j.isci.2022.104797
• 发表时间: 2022-09-16
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Battistella, Eliana;Schniete, Jan;Wesencraft, Katrina;Quintana, Juan F.;McConnell, Gail
• 通讯作者: McConnell, Gail

Widefield Two-Photon Excitation without Scanning: Live Cell Microscopy with High Time Resolution and Low Photo-Bleaching.

• DOI: 10.1371/journal.pone.0147115
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Amor R;McDonald A;Trägårdh J;Robb G;Wilson L;Abdul Rahman NZ;Dempster J;Amos WB;Bushell TJ;McConnell G
• 通讯作者: McConnell G