A multiplexed tissue imaging platform @Newcastle University for mapping cell types, states and interactions in human development, health and disease

细胞是生命的基石。人体被认为含有大约37.2万亿个细胞，每个细胞都在决定我们的健康和寿命方面发挥着作用。不同类型的细胞具有特殊的功能，如允许我们移动的肌肉细胞，允许我们控制身体的脑细胞，以及对抗感染的免疫细胞。在某些情况下，即使一个细胞在体内以不正常的“反社会”方式行为，也可能导致灾难性的结果，如癌症、神经退化和自身免疫，即身体攻击自己。在过去的几年里，可以测量单个细胞的多种属性的技术有助于促进我们对单个细胞和细胞的群落/结构在正常和异常条件下的行为的理解。“细胞学”一词的字面意思是“细胞测量”，而希腊语“Kytos”的意思是“细胞”，“metria”的意思是“测量”。当我女儿8岁的时候，她问我是做什么工作的。我告诉她我是一名“细胞测量学家”，我的工作就是“审问”细胞，找出它们一直在做什么，以及这是否做了什么坏事。她想了想，回答说：“这意味着你是一名细胞侦探爸爸。”从那时起，这个比喻真的让我印象深刻，因为它解释了我完美地做了什么。我使用各种技术来审问大量的细胞，并试图找到我的疾病(犯罪)嫌疑人名单。直到最近，人们还只能使用所谓的“悬浮”技术对我们的细胞提出许多问题，即细胞必须在液体中。这对像血液样本这样的东西很好，但不适用于我们想要测量组织中细胞的情况，因为这需要我们分解结构并释放单个细胞进行分析。这有几个主要问题1)它可以杀死样本中的某些或所有细胞，2)它可以改变样本中的细胞，使它们获得或失去重要蛋白质/基因的表达，从而掩盖它们的身份，3)你失去了细胞在组织中相对于其邻居的空间位置，使得现在几乎不可能将可疑细胞放置在犯罪现场。我们所要求的技术的力量将使我们能够做到这一点。它将有能力对组织空间中的细胞提出尽可能多的问题，即使不是更多，就像我们在悬浮状态下所能提出的那样，但重要的是保持空间背景和细胞邻域。换个比喻，悬浮技术就像棋盘游戏《猜猜谁》，但空间技术更像游戏《Cluedo》。我们可以在犯罪现场找到嫌疑人和地点；如果我们要解决严重而紧迫的人类健康和疾病问题，这是绝对必要的。我们要求的平台是尖端的，将是英国仅有的两个平台之一。它将在一个非常有经验的核心设施内得到技术专家的支持，并将有助于他们的职业发展。这非常符合英国政府科学理事会的“技术人员承诺”，以及在学术和工业环境中留住、培养和增加技术人员数量的迫切需要。我们将使用这项技术来询问多种人类疾病以及从卵子到胎儿的不同发育阶段的细胞。这些数据将对我们对人类健康、发展和疾病的理解产生深远影响，并有助于发现可能的治疗目标。

Cells are the building blocks of life. The human body is thought to contain around 37.2 trillion cells and each one plays a role in determining our health and longevity. Different cell types have specialised functions such as muscle cells that allow us to move, brain cells that allow us to control our bodies, and immune cells that fight infection. In certain situations, even one cell behaving in an abnormal "anti-social" way in the body can lead to catastrophic outcomes such as cancer, neurodegeneration and auto-immunity; where the body attacks itself. Over the last few years, technologies that can measure multiple properties of single cells have been instrumental in advancing our understanding of how individual cells and communities/structures of cells behave both in normal and abnormal conditions. The word "cytometry" literally translates to "Cell Measurement" from the Greek words "Kytos" meaning "cell" and "metria" meaning "to measure". When my daughter was 8 years old, she asked me what I do for a job. I told her I was a "cytometrist" and it was my job to "interrogate" cells to find out what they have been doing and whether that had done something bad. She thought about this and replied, "That means you are a Cell Detective Daddy". Since then this analogy has really stuck with me as it explains what I do perfectly. I use various technologies to interrogate large populations of cells and try to find my list of suspects in a disease (crime). Until recently, it was only possible to ask many questions of our cells using so called "suspension" technologies where the cells had to be in a liquid. This was fine for things like blood samples, but not for situations where we wanted to measure cells in tissue, as it required us to break the structures down and release the individual cells for analysis. There are several major issues with this 1) It can kill certain or all cells in the sample, 2) It can change the cells in the sample making them gain or lose expression of important proteins/genes thus disguising their identity, 3) You lose the spatial location of the cell in the tissue with respect to its neighbours making it near impossible to now place the suspect cell at the crime scene. The power of the technology we are requesting will allow us to do just that. It will have the capability to ask as many if not more questions of cells in the tissue space as we could in suspension, but importantly preserve the spatial context and cellular neighbourhoods. To use another analogy, suspension technologies are like the board game "Guess Who", but spatial technologies are more like the game "Cluedo". We can find both the suspect and place then at the crime scene; this is utterly essential if we want to solve serious and pressing issue sin human health and disease. The platform we are requesting is cutting-edge and will be one of only two in the UK. It will be supported technical specialists within a very experienced, core facility and will help to develop their careers. This is very much in line with the UK government Science Council's "technician commitment" and an urgent need to retain, develop and increase the number of technicians within academic and industrial settings.We will use this technology to interrogate cells across numerous human diseases as well as different developmental stages from Oocyte to foetus. The data will have a profound impact on our understanding of human health, development and disease and help to uncover possible targets for treatment.