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

纽卡斯尔大学的多重组织成像平台，用于绘制人类发育、健康和疾病中的细胞类型、状态和相互作用

• 批准号: MR/X011895/1
• 负责人: Andrew Filby
• 金额: $ 61.59万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX011895%2F1
• 关键词: multiplexed; tissue; imaging; platform; Newcastle

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.

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作用。不同类型的细胞具有专门的功能，例如使我们能够移动的肌肉细胞，使我们能够控制身体的脑细胞，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异常的“反社会”方式表现，也可能导致灾难性的结果，如癌症，神经退行性变和自身免疫;身体攻击自己。在过去的几年里，可以测量单细胞的多种特性的技术有助于促进我们对单个细胞和细胞群落/结构在正常和异常条件下的行为的理解。“细胞仪”一词从希腊语“Kytos”（意为“细胞”）和“metria”（意为“测量”）字面上翻译为“细胞测量”。当我女儿8岁的时候，她问我做什么工作。我告诉她我是一名“细胞测量师”，我的工作是“审问”细胞，以找出它们在做什么以及是否做了坏事。她想了想，回答说：“那就是说你是一个细胞侦探爸爸。从那时起，这个类比就一直困扰着我，因为它完美地解释了我所做的事情。我使用各种技术来询问大量的细胞，并试图找到我的疾病（犯罪）嫌疑人名单。直到最近，人们才有可能使用所谓的“悬浮”技术来询问我们的细胞的许多问题，其中细胞必须处于液体中。这对于血液样本之类的东西来说是很好的，但对于我们想要测量组织中细胞的情况来说就不行了，因为它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在犯罪现场。我们所要求的技术力量将使我们能够做到这一点。它将有能力问尽可能多的问题，如果不是更多的问题，在组织空间中的细胞，因为我们可以在悬浮液中，但重要的是保留空间背景和细胞邻域。用另一个比喻来说，悬挂技术就像棋盘游戏“猜猜谁”，但空间技术更像游戏“Cumbrido”。我们可以在犯罪现场找到嫌疑人和地点;如果我们想解决人类健康和疾病中严重而紧迫的问题，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支持技术专家，并将帮助他们发展职业生涯。这与英国政府科学理事会的“技术人员承诺”非常一致，也是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母细胞到胎儿的不同发育阶段的细胞。这些数据将对我们理解人类健康、发展和疾病产生深远影响，并有助于发现可能的治疗目标。