Developing a real-time live cell imaging platform at Newcastle University

纽卡斯尔大学开发实时活细胞成像平台

• 批准号: MR/X012360/1
• 负责人: Kelly Coffey
• 金额: $ 77.67万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX012360%2F1
• 关键词: Developing; real; time; live; cell

Understanding how cells respond in real-time to their environment is a key observation in many disciplines of medical research. For example, understanding how cancer cells respond to novel drug treatments or how immune cells interact with other cell types in autoimmune disease. Simple incubator-based microscope-based platforms have existed for many years and have allowed us to monitor in real-time the behaviour of cells by following changes in: shape, division, migration and proliferation. Technology in this area has now vastly improved and combined with AI-driven image analysis algorithms, we are now able to study much more complex behaviours and with much greater throughput. The Incucyte SX5 is a long-term live cell real-time microscopy platform that will enhance our research capabilities across a number of research fields at Newcastle University. By housing this platform within our established Bioimaging Unit, we can offer expert advice on experimental set up and data analysis and guarantee that the platform will be supported and used optimally throughout its operational lifespan. The ability of this machine to perform 6 independent studies concurrently provides superior multi-user capabilities over previous Incucyte generations which could only run one type of assay at a time. Research that will be carried out using this equipment includes the study of globally significant diseases where Newcastle University scientists are world-leaders these include: multiple cancer types (Newcastle Centre for Cancer), mitochondrial disorders (Wellcome Centre for Mitochondrial Research), respiratory, neurodegenerative and liver diseases. Using the Incucyte SX5, we not only carry out established and optimised experiments (using the previous-generation Incucyte Zoom technology) but will expand on them to incorporate complex kinetic measurements. For example, individual cellular analysis can now be performed which improves the accuracy of proliferative and migratory data. We can combine this with both drug and CRISPR screening to identify new therapeutic targets for disease. With the ability to detect up to 5 fluorescence colours the experimental capabilities are further enhanced. For example, cell cycle phase can be recorded in real-time, co-culture studies can be carried out such as visualisation and quantification of tumour-immune cell interactions to interrogate advanced therapeutic interventions. Excitingly, robust and consistent evaluation of 3D cell cultures is now possible and will be performed by a number of research groups which will increase the impact of their research programs and help deliver new disease models for their research field. With a strong neuroscience research base in Newcastle, there is a demand to access neuronal activity assays which only the SX5 model can offer. Similarly, ATP metabolism assays can be performed which are highly useful to our world-leading mitochondrial research teams.In line with the principles developed by Newcastle University in its commitment to become carbon neutral by 2030, the cross-campus imaging platform developed will result in the removal, re-use (for spare parts) and recycling of existing older systems. It will also make use of existing incubators and require no further lab modifications or services. The platform will be networked to facilitate remote monitoring and experimental set-up. It will also reduce the requirement for staff to regularly transport across campus as well as duplicate experiments, media and reagents.

了解细胞如何实时响应其环境是许多医学研究学科的关键观察。例如，了解癌细胞如何对新药治疗作出反应，或者免疫细胞如何与自身免疫性疾病中的其他细胞类型相互作用。简单的基于培养箱的显微镜平台已经存在多年，并使我们能够通过以下变化实时监测细胞的行为：形状，分裂，迁移和增殖。这一领域的技术现在已经得到了极大的改进，并与人工智能驱动的图像分析算法相结合，我们现在能够研究更复杂的行为，并具有更大的吞吐量。Incucyte SX 5是一个长期的活细胞实时显微镜平台，将提高我们在纽卡斯尔大学多个研究领域的研究能力。通过将该平台安装在我们已建立的生物成像单元中，我们可以提供有关实验设置和数据分析的专家建议，并保证该平台在其整个运行寿命期间得到最佳支持和使用。该机器能够同时执行6项独立研究，与之前一次只能运行一种类型的检测试剂盒的Incucyte代相比，提供了上级多用户功能。将使用该设备进行的研究包括对全球重大疾病的研究，其中纽卡斯尔大学的科学家处于世界领先地位，其中包括：多种癌症类型（纽卡斯尔癌症中心）、线粒体疾病（惠康线粒体研究中心）、呼吸道、神经退行性和肝脏疾病。使用Incucyte SX 5，我们不仅可以进行已建立和优化的实验（使用上一代Incucyte Zoom技术），而且还可以扩展它们以纳入复杂的动力学测量。例如，现在可以进行个体细胞分析，这提高了增殖和迁移数据的准确性。我们可以将其与药物和CRISPR筛选相结合，以确定疾病的新治疗靶点。随着检测多达5种荧光颜色的能力，实验能力进一步增强。例如，可以实时记录细胞周期阶段，可以进行共培养研究，例如肿瘤-免疫细胞相互作用的可视化和定量，以询问先进的治疗干预。令人兴奋的是，现在可以对3D细胞培养物进行稳健和一致的评估，并将由许多研究小组进行，这将增加其研究计划的影响力，并有助于为其研究领域提供新的疾病模型。由于纽卡斯尔拥有强大的神经科学研究基地，因此需要访问只有SX 5模型才能提供的神经元活动测定。同样，ATP代谢分析也可以进行，这对我们世界领先的线粒体研究团队非常有用。根据纽卡斯尔大学制定的到2030年实现碳中和的原则，开发的跨校园成像平台将导致现有旧系统的移除、再利用（作为备件）和回收。它还将利用现有的孵化器，不需要进一步的实验室改造或服务。该平台将联网，以便利远程监测和实验设置。它还将减少工作人员定期在校园内运输以及重复实验、培养基和试剂的需求。

项目成果

The catalytic subunit of DNA-PK regulates transcription and splicing of AR in advanced prostate cancer.

• DOI: 10.1172/jci169200
• 发表时间: 2023-11-15
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Adamson, Beth;Brittain, Nicholas;Walker, Laura;Duncan, Ruaridh;Luzzi, Sara;Rescigno, Pasquale;Smith, Graham;McGill, Suzanne;Burchmore, Richard J. S.;Willmore, Elaine;Hickson, Ian;Robson, Craig N.;Bogdan, Denisa;Jimenez-Vacas, Juan M.;Paschalis, Alec;Welti, Jonathan;Yuan, Wei;McCracken, Stuart R.;Heer, Rakesh;Sharp, Adam;de Bono, Johann S.;Gaughan, Luke
• 通讯作者: Gaughan, Luke