Taking super resolution microscopy beyond the laboratory

将超分辨率显微镜带出实验室

• 批准号: MR/S03241X/1
• 负责人: Izzy Jayasinghe
• 金额: $ 118.07万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS03241X%2F1
• 关键词: Taking; super; resolution; microscopy; beyond

In this fellowship, I will build a new portable imaging technology which will allow scientists, medical doctors, conservationists and industrial parties to visualise the smallest building blocks of any biological sample from any location. The UK and other governments are currently making urgent investments into understanding the role of molecules and cells in the "Global Challenges" which include the effects of climate change on food sources and lifestyle effects on major human diseases and ageing. Despite this urgency, we remain unable to visualise the relevant genes, proteins and cellular components in their natural environments or the geographical locations of the problem. Frustratingly, the technology for visualising such minute structures exists. It is called 'super-resolution microscopy' and we even hailed its invention with a Nobel Prize in 2014. However, it has remained beyond the reach of field scientists and clinicians because it has always relied upon specialist skill for its operations and expensive and bulky equipment for its implementation. In this fellowship, I will use a radically new approach to make super-resolution microscopy portable, cheap and easy to use. I will harness a novel chemical reaction which allows any scientists to physically inflate a desired feature of a sample, for example a patient biopsy or a small organism, by 200 to 3000-fold in volume. I will build a set of molecular tools and a miniaturised transparent enclosure within which the desired sample can be inflated under full computer control. With the physical inflation of the sample, its finer features will then become easy to visualise with a simple microscope. To this end, I will build a miniaturised optical microscope which can acquire precise digital images of the cells, tissues or organism which were previously too small to be visualised with traditional optical microscopes. To refine and ensure that this device delivers this claimed imaging capability, I will carry out case studies in partnership with experts whose samples are collected outside of the academic laboratory (in Phase II). They include a field scientist who will use it to examine young sea urchins in the UK coast, doctors and sports scientists who will screen for the fine structure of needle biopsies taken in the clinic from human patients, and a partner of the European space programme who will use it to remotely study the effect 'zero gravity' on the ageing of microscopic worms sent between earth and the international space station. Beyond the timeline of the fellowship, I will develop this technology into a handheld device which will become a part of the repertoire of any scientist, doctor or field surveyor who wishes to study life in the sub-microscopic scale outside of the walls of the laboratory. Applied to the "Global Challenges", this technology will broaden their ability to visualise and target cells and molecules to find the solutions that humankind urgently needs. I apply for this fellowship as the ideal candidate to develop this tool, having acquired 11 years of experience in adopting and refining super-resolution microscopy. This fellowship will provide a critical springboard to developing this transformative technology by affording me (i) an interdisciplinary skill base required for building the tool and (ii) the opportunity to partner with the end-users of the technology throughout the complete programme of tool building and field testing.

在这个奖学金，我将建立一个新的便携式成像技术，这将允许科学家，医生，环保主义者和工业党可视化的任何生物样本的最小的积木从任何位置。 英国和其他国家政府目前正在进行紧急投资，以了解分子和细胞在“全球挑战”中的作用，包括气候变化对食物来源的影响以及生活方式对主要人类疾病和衰老的影响。尽管如此紧迫，我们仍然无法在自然环境或问题的地理位置中可视化相关的基因，蛋白质和细胞成分。令人沮丧的是，可视化这种微小结构的技术存在。它被称为“超分辨率显微镜”，我们甚至在2014年获得了诺贝尔奖。然而，它仍然超出了现场科学家和临床医生的能力范围，因为它一直依赖于专业技能的操作和昂贵和笨重的设备来实施。 在这个奖学金中，我将使用一种全新的方法，使超分辨率显微镜便携，廉价和易于使用。我将利用一种新的化学反应，使任何科学家都可以物理膨胀样品的所需特征，例如患者活检或小生物体，体积增加200至3000倍。我将建造一套分子工具和一个密封的透明外壳，在完全计算机控制下，所需的样品可以在其中膨胀。随着样品的物理膨胀，其更精细的特征将变得很容易用简单的显微镜观察。为此，我将建立一个自动化的光学显微镜，它可以获取细胞，组织或生物体的精确数字图像，这些图像以前太小，无法用传统的光学显微镜观察。为了完善并确保该设备提供这种声称的成像能力，我将与专家合作进行案例研究，这些专家的样本是在学术实验室之外收集的（在第二阶段）。他们包括一位实地科学家，他将用它来检查英国海岸的年轻海胆，医生和体育科学家，他们将筛选在诊所从人类患者身上取下的针活检的精细结构，以及欧洲太空计划的合作伙伴，他们将用它来远程研究“零重力”对地球和国际空间站之间发送的微观蠕虫衰老的影响。在奖学金的时间轴之外，我将把这项技术发展成一种手持设备，它将成为任何科学家、医生或实地调查员的一部分，他们希望在实验室墙壁之外的亚微观尺度上研究生命。应用于“全球挑战赛”，这项技术将扩大他们可视化和靶向细胞和分子的能力，以找到人类迫切需要的解决方案。 我申请这个奖学金作为开发这个工具的理想候选人，在采用和改进超分辨率显微镜方面获得了11年的经验。该奖学金将为开发这种变革性技术提供一个重要的跳板，为我提供（i）构建工具所需的跨学科技能基础，以及（ii）在整个工具构建和现场测试的完整计划中与技术的最终用户合作的机会。

项目成果

Cysteine post-translational modifications regulate protein interactions of caveolin-3

半胱氨酸翻译后修饰调节 Caveolin-3 的蛋白质相互作用

• DOI: 10.1101/2022.09.15.508083
• 发表时间: 2022
• 作者: Ashford F

Increased SERCA2a sub-cellular heterogeneity in right-ventricular heart failure inhibits excitation-contraction coupling and modulates arrhythmogenic dynamics.

• DOI: 10.1098/rstb.2021.0317
• 发表时间: 2022-11-21
• 期刊: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 6.3
• 作者: Holmes, M.;Hurley, M. E.;Sheard, T. M. D.;Benson, A. P.;Jayasinghe, I.;Colman, M. A.
• 通讯作者: Colman, M. A.

Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.

• DOI: 10.1098/rsob.230045
• 发表时间: 2023-05
• 期刊: Open biology
• 影响因子: 5.8

Self-activated photoblinking of nitrogen vacancy centers in nanodiamonds (sandSTORM): A method for rapid single molecule localization microscopy with unlimited observation time

• DOI: 10.1101/2020.05.20.106716
• 发表时间: 2020-05
• 期刊: bioRxiv
• 作者: Kaarjel K. Narayanasamy;J. Price;Raquel Mesquita-Riberio;M. Mather;I. Jayasinghe

Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease

心脏钙火花及其在健康和疾病中的分子起源的相关超分辨率分析

• DOI: 10.1101/2023.02.12.528168
• 发表时间: 2023
• 作者: Hurley M