Functional Imaging of Barrier Function in 2D and 3D epithelia

2D 和 3D 上皮细胞屏障功能的功能成像

• 批准号: 2880659
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2880659
• 关键词: Functional; Imaging; Barrier; Function; 2D

This project aims to create next-generation drug discovery platforms to characterise barrier function in microphysiological models of epithelial barrier tissues non-invasively. The pharmaceutical industry is increasingly shifting away from animal studies towards cell assays based on human or human-derived cells. Reasons are both ethical and practical, since human cells more accurately mimic human cell tissue behaviour and responses. This saves time and money in drug development pipelines and helps to de-risk lead advancement by providing early data on potential human side-effects. Next generation platform technologies are urgently needed to extract real-time data from "microphysiological" systems, which are being developed through "tissue on chip" approaches. However, we presently lack the ability to combine key physiological requirements such as porosity, polarity, fluidic access, and electrode access with the optical transparency and small dimensions required to achieve scalable manufacture at tractable cost. This project will develop novel imaging and sensing methods to compliment techniques developed at Nottingham (electro-impedance imaging, hydrodynamic Raman imaging) to monitor and characterise electrical molecular barrier function in epithelial (skin) barrier tissue models in routine use in the Webb lab (lung: Calu-3, eye: ARPE-19, gut: Caco-2). Physiological parameters of cell systems using industry-standard methods (Transwell) will be compared with novel advanced materials such as nanoporous nitride (NPN) membranes and microporous bioglasses developed herein, on which 2D and 3D epithelial cultures will be established and characterised. Gold-standard methods will provide quantitative data demonstrating the potential of these novel platforms for the monitoring of physiology in a high-throughput context. We will leverage existing links to UoN IP and potential commercialisation pathways for NPN biosensors, microporous glasses, electroimpedance imaging methods, biocompatible surface coatings, and microphysiological devices to generate an advanced platform for the sensitive and non-invasive monitoring of physiology during exposure to pharmacological (drug candidates, permeation enhancing systems) and physiological (ion replacement, osmotic manipulation) challenges.

该项目旨在创建下一代药物发现平台，以表征非侵入性上皮屏障组织的微生物生理模型中的屏障功能。制药行业越来越多地从动物研究转移到基于人类或人类衍生细胞的细胞分析。原因既是伦理又实用，因为人类细胞更准确地模仿了人类细胞组织的行为和反应。这样可以节省药物开发管道中的时间和金钱，并通过提供潜在的人类副作用的早期数据来帮助脱离风险的铅进步。迫切需要下一代平台技术从“微生物生理”系统中提取实时数据，这些数据是通过“芯片上的组织”方法开发的。但是，我们目前缺乏结合关键生理要求的能力，例如孔隙率，极性，流体通道和电极访问，以及以可拖动成本实现可扩展制造所需的光学透明度和较小的尺寸。该项目将开发出新的成像和传感方法，以补充诺丁汉（电势成像，流体动力拉曼成像）开发的技术，以监视和表征上皮分子屏障功能（皮肤）屏障组织在常规中的屏障组织中的电气屏障功能（webb实验室中）（lung-3，calu-3，calu-3，eye：arpe-3，arpe-119，gut：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco：caco-2）。使用行业标准方法（Transwell）的细胞系统的生理参数将与新的先进材料（例如纳米多孔氮化物（NPN）膜和本文开发的微孔野生相提并论）进行比较，其中将建立2D和3D上皮培养物。黄金标准方法将提供定量数据，证明这些新型平台在高通量环境中监测生理学的潜力。我们将利用NPN生物传感器，微孔玻璃，电浪费成像方法，生物相容性的表面涂层和微生物生理设备的现有链接以及潜在的商业化途径，以生成对敏感和非侵入性监测物质的敏感和非侵入性监测的高级平台（渗透性（Pressigation），渗透性（渗透性）（渗透性），渗透性（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性）（渗透性），培养eatione（pressigion））操纵）挑战。