Understanding host interactions with high consequence pathogens using super resolution light microscopy in biocontainment.

这项研究计划是为了一种名为细胞发现者7号的实验室设备。这是一种显微镜，可以让我们看到细胞内部的情况。这一点至关重要，因为病毒等对动物和人类健康至关重要的传染病在细胞内工作，我们需要实时观察它们是如何工作的，以便更好地开发机制来阻止它们。这台设备对我们来说很重要，因为我们想用它来研究在遏制水平上影响人类和动物健康的传染病(CL3)。目前，据我们所知，政府支持的研究机构或大学还没有这样的设施。CL3是一种安全处理对人类和/或动物健康构成更大威胁的危险病原体的方法。例如，SARS-CoV-2，某些流感病毒，许多我们从蚊子那里感染的传染病和结核病(TB)等细菌。在CL3工作并不容易，而且出于安全考虑，您可以进行的实验受到限制。目前的技术水平是，任何感染的图像都来自灭活的样本-这会导致图像/图片扭曲，没有现场工作。细胞发现者7具有一些独特的功能，允许真正的一步改变，使我们能够真正推进我们对人和动物的高后果传染病的研究。这种先进的显微镜将使我们能够实时跟踪传染病的蛋白质和影响，例如，在生物中。后一个特征是真正重要的一个--因为这是以前在高遏制下从未做过的。我们将确定治疗性化合物在阻止疾病进展方面是否有效，并确定我们未来可能针对的传染病生命周期的基本部分。由于这种显微镜的独特功能和我们在CL3使用它的能力，我们收到了许多来自研究委员会/政府支持的研究所和大学的支持信，我们将在那里充当研究酒店和培训设施。这将真正推动英国科学的竞争力，更重要的是，这将使我们能够应对即将到来的传染病挑战。这些疾病包括人畜共患传染病(我们从动物身上传染的疾病)，气候变化引起的媒介传播疾病(我们从蚊子之类的东西传染的疾病)，以及研究抗微生物耐药性。

This research proposal is for a piece of laboratory equipment called a Cell Discoverer 7. This is a microscope that allows us to see within cells. This is vital because infectious diseases important to animal and human health, such as viruses, work inside cells, and we need to see how they work in real time in order to better develop mechanisms to stop them. This equipment is important for us as we want to use it to study infectious diseases that impact on human and animal health at Containment Level (CL3). Currently, to our knowledge, there is no such facility in government supported research institutes or Universities. CL3 is a way of working safely with dangerous pathogens that pose a greater threat to human and/or animal health. Examples include, SARS-CoV-2, certain influenza viruses, many infectious diseases that we get from mosquitoes and bacteria like tuberculosis (TB). Working at CL3 is not easy and the experiments you can do are limited by safety considerations. Currently the state of the art is that any images of infection are from inactivated specimens - this leads to distortion of images/pictures and no live work. The Cell Discoverer 7 has some unique features that allow a real step change and allow us to really advance our research on high consequence infectious diseases of humans and animals. This advanced microscope will allow us to follow the proteins and effects of infectious diseases in real time e.g., in living things. This latter feature is the really important one - as this has not been done before at high containment. We will be to determine whether therapeutic compounds are effective in stopping disease progression as well as identify fundamental parts of the infectious disease lifecycle that we could target in the future. Because of the unique features of this microscope and our ability to use it at CL3, we have many letters of support from Research Council/Government supported Institutes and Universities where we would act as a research hotel and training facility. This would really drive forward the competitiveness of UK science and more importantly allow us to deal with the infectious disease challenges that are on the horizon. These include zoonotic infections (diseases that we get from animals), vector borne diseases due to climate change (diseases that we get from things like mosquitoes) and studying anti-microbial resistance.