A Facility for Advanced Imaging and Analysis under Hypoxic Conditions for Bath Scientists and GW4 partners

为巴斯科学家和 GW4 合作伙伴提供缺氧条件下的高级成像和分析设施

• 批准号: BB/M012409/1
• 负责人: Amanda MacKenzie
• 金额: $ 35.81万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM012409%2F1
• 关键词: Facility; Advanced; Imaging; Analysis; under

We wish to develop a unique and cutting edge facility in Bath to enable us to study the impact that low oxygen conditions (hypoxia) have on cell function. Oxygen is vital for life and inspired from air. In a healthy individual, oxygen levels in the circulation are lower than atmospheric and decrease further depending on how far from the blood supply. For example some brain tissue and skin layers are a significant distance from a blood supply. In the normal situation, oxygen levels in most tissues would be considered low (hypoxic) compared to atmospheric oxygen levels. At sites of inflammation the level of oxygen decreases further due to increased oxygen usage by cells and a reduced blood supply. These changes affect the function of many tissues including the brain which is particularly susceptible to hypoxia resulting from transient ischemic episodes or impaired blood flow during aging. The level of oxygen dramatically alters many cell properties, including the genes expressed and protein function. In modern science it is essential to derive accurate models of cell function in the lab so results can be translated to the living system. In many lab-based experiments, isolated cells are cultured in atmospheric oxygen levels that do not reflect the environment encountered in the healthy body. The 'advanced hypoxic imaging facility' will use high performance imaging and analytical equipment with user defined oxygen levels to study different aspects of cell function. This state of the art approach represents a significant technical advance that will enable us to very accurately mimic the hypoxic conditions that occur in humans in our cellular model systems. The instruments will measure: (1) activity of single cells with an ultrasensitive, high speed detection camera; (2) multiple conditions using a high-throughput reader with a revolutionary technology for increased detection sensitivity; and (3) modified oxygen species using 'electron spin resonance'. The proposal includes five specific projects to measure the properties of immune cells found at the sites of inflammation, brain cells and cells that form blood vessels. The instruments will form part to the Bio-imaging Suite in the Microscopy and Analysis Suite in the University of Bath. The user community will include scientists in the South West and South Wales.

我们希望在巴斯开发一个独特的尖端设施，使我们能够研究低氧条件（缺氧）对细胞功能的影响。氧气对生命至关重要，并从空气中汲取。在健康的个体中，循环中的氧气水平低于大气，并根据离血液供应的距离进一步降低。例如，一些脑组织和皮肤层距离血液供应有很大的距离。在正常情况下，与大气氧水平相比，大多数组织中的氧水平被认为是低的（缺氧）。在炎症部位，由于细胞的氧气使用增加和血液供应减少，氧气水平进一步降低。这些变化影响许多组织的功能，包括大脑，大脑特别容易受到短暂性缺血发作或衰老期间血流受损引起的缺氧的影响。氧气水平会显著改变许多细胞特性，包括表达的基因和蛋白质功能。在现代科学中，必须在实验室中推导出细胞功能的精确模型，以便将结果转化为生命系统。在许多基于实验室的实验中，分离的细胞在大气氧水平下培养，这并不反映健康身体所遇到的环境。“先进的缺氧成像设施”将使用具有用户定义的氧气水平的高性能成像和分析设备来研究细胞功能的不同方面。这种最先进的方法代表了一个重大的技术进步，将使我们能够非常准确地模拟在我们的细胞模型系统中发生在人类中的缺氧条件。这些仪器将测量：（1）使用超灵敏的高速检测相机检测单细胞活性;（2）使用具有革命性技术的高通量读取器检测多种条件以提高检测灵敏度;以及（3）使用“电子自旋共振”修饰氧物质。该提案包括五个具体项目，以测量在炎症部位发现的免疫细胞，脑细胞和形成血管的细胞的特性。这些仪器将成为巴斯大学显微镜和分析套件中生物成像套件的一部分。用户社区将包括西南部和南威尔士的科学家。

项目成果

Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus aureus Inhibits the Formation of Platelet-Leukocyte Complexes.

• DOI: 10.1074/jbc.m115.678359
• 发表时间: 2016-02-05
• 期刊: The Journal of biological chemistry
• 作者: Posner MG;Upadhyay A;Abubaker AA;Fortunato TM;Vara D;Canobbio I;Bagby S;Pula G
• 通讯作者: Pula G

Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis.

• DOI: 10.1089/ars.2016.6869
• 发表时间: 2018-01-10
• 期刊: Antioxidants & redox signaling
• 影响因子: 6.6
• 作者: Vara D;Watt JM;Fortunato TM;Mellor H;Burgess M;Wicks K;Mace K;Reeksting S;Lubben A;Wheeler-Jones CPD;Pula G
• 通讯作者: Pula G