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

我们希望在巴斯开发一种独特的尖端设备，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，它的灵感来自空气。在健康的个体中，循环中的氧气水平低于大气中的氧气水平，并根据距离血液供应的距离而进一步下降。例如，一些脑组织和皮肤层与血液供应有很大的距离。在正常情况下，大多数组织的含氧量与大气含氧量相比被认为是低(低氧)的。在炎症部位，由于细胞用氧量增加和血液供应减少，氧气水平进一步下降。这些变化影响到许多组织的功能，包括大脑，大脑特别容易受到短暂性脑缺血发作或衰老过程中血液流动障碍引起的缺氧的影响。氧气水平极大地改变了许多细胞特性，包括基因表达和蛋白质功能。在现代科学中，在实验室中推导出细胞功能的准确模型是必不可少的，这样结果才能转化为生命系统。在许多以实验室为基础的实验中，分离的细胞是在大气中的氧气水平下培养的，这并不反映健康身体所遇到的环境。先进的低氧成像设备将使用高性能成像和分析设备，用户定义的氧气水平，以研究细胞功能的不同方面。这种最先进的方法代表了一项重大的技术进步，它将使我们能够非常准确地在我们的细胞模型系统中模拟发生在人类身上的缺氧条件。这些仪器将测量：(1)具有超灵敏高速检测相机的单细胞活性；(2)使用具有革命性技术的高通量读取器提高检测灵敏度的多种条件；以及(3)使用‘电子自旋共振’修饰氧物种。该提案包括五个具体项目，以测量在炎症部位、脑细胞和形成血管的细胞中发现的免疫细胞的特性。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。

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.