Development and characterisation of multi-cellular lung organoids for use in Bovine TB research

用于牛结核病研究的多细胞肺类器官的开发和表征

• 批准号: 2902257
• 金额: --
• 依托单位: University of Edinburgh
• 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-2902257
• 关键词: Development; characterisation; multi; cellular; lung

Despite decades of research, Bovine Tuberculosis (BTb) continues to cause significant animal welfare and economic issues globally. Caused by the intracellular bacterium Mycobacterium bovis, this zoonotic pathogen also infects and causes disease in humans and multiple animal species. Current diagnostic tools, vaccination and treatment options are not ideal; resulting in a continued reliance on the 'test and cull' strategy in the UK.In this project, we aim to optimise the production of multi-cellular bovine lung organoids derived from bovine stem cells, and/or abattoir material, with the ultimate goal of reducing the numbers of live animals used in BTb research. These 'lungs-in-a-dish' (Archer et al. 2021, doi: 10.1186/s13567-021-00946-6) will be extensively characterised by comparing their cellular composition with bovine lung tissue, using a variety of approaches such as immunohistochemistry and quantitative RT-PCR techniques. Once the conditions for optimal organoid production are established, this project will be extended to study the interaction of M. bovis strains obtained from diverse locations within the UK which differ in virulence cattle, and in their ability to survive and replicate in bovine macrophages (Jensen et al. 2018, doi: 10.1128/IAI.00385-17; Jensen et al. 2020, doi: 10.1371/journal.pone.0222437). Cellular responses and the survival of the bacterium over time will be studied. In addition the interaction of infected cells with mucosal innate immune cells, which will be provided in co-culture, will also be explored. The information deriving from these studies will be invaluable in the development of more specific and sensitive diagnostic tools for BTb and provide important insights into the immunobiology of the lung: M. bovis interaction required for the smart design of future vaccination strategies.

尽管经过数十年的研究，牛结核病（BTb）仍在全球范围内造成重大的动物福利和经济问题。由细胞内细菌牛分枝杆菌引起，这种人畜共患病原体也感染人类和多种动物物种并引起疾病。目前的诊断工具、疫苗接种和治疗方案并不理想;导致英国继续依赖“检测和剔除”策略。在本项目中，我们的目标是优化从牛干细胞和/或屠宰场材料中提取的多细胞牛肺类器官的生产，最终目标是减少BTb研究中使用的活动物数量。这些“培养皿中的肺”（Archer等人，2021，doi：10.1186/s13567-021-00946-6）将通过使用多种方法（如免疫组织化学和定量RT-PCR技术）将其细胞组成与牛肺组织进行比较来进行广泛表征。一旦建立了最佳类器官产生的条件，该项目将扩展到研究M。从英国不同地点获得的牛菌株，其毒力牛以及在牛巨噬细胞中存活和复制的能力不同（詹森et al. 2018，doi：10.1128/IAI.00385-17;詹森et al. 2020，doi：10.1371/journal.pone.0222437）。将研究细胞反应和细菌随时间的存活。此外，还将探索感染细胞与将在共培养中提供的粘膜先天免疫细胞的相互作用。从这些研究中获得的信息对于开发更特异和灵敏的BTb诊断工具将是非常宝贵的，并为肺的免疫生物学提供重要的见解：M。未来疫苗接种策略的智能设计所需的牛的相互作用。