Leveraging the spectral sorting revolution to gain deeper insights into cellular and tissue biology

人类和其他复杂的生物体是由数十亿个称为细胞的个体组成的。虽然这些细胞具有某些共同特征，但它们通常也是高度专业化的，从构成我们大脑的神经元，到将氧气从肺部运送到身体其他部位的红细胞，再到排列在我们肠道内并从我们所吃的食物中吸收营养的上皮细胞。了解这些细胞如何发展这种特殊功能是生物学研究面临的一个基本问题，有助于我们了解生命本身的基本规则。科学家用来了解细胞如何发育和功能的一种技术是根据某些特征将它们分离，特别是它们制造的专门蛋白质，这些蛋白质在不同的细胞类型之间可能存在显着差异。细胞内的不同蛋白质可以使用具有特定荧光颜色（例如红色、蓝色或绿色）的蛋白质或染料来“标记”。然后，一种称为细胞分选仪的专用设备可以使用检测器来“读取”每个细胞产生的荧光量，并根据其荧光信号的组合将每个细胞物理分选到不同的试管中。通过这种方式，细胞分选机可以将不同细胞类型的复杂混合物分成组，以便科学家可以分别研究每种细胞类型。我们正在申请资金，在剑桥医学研究所（CIMR）现有的核心设施中安装一台新的细胞分选机，CIMR的研究人员将在那里使用它，剑桥干细胞研究所和整个剑桥大学及周边地区。核心设施非常忙碌，被两个申请研究所的50多个研究团队中的许多学生和研究人员使用。我们购买新的分拣机是至关重要的，因为我们目前的分拣设备正在老化并迅速过时，事实上，两年后制造商将不再支持。然而，虽然我们必须获得一个替代分拣机，但我们要求的特定设备，大脚光谱分拣机，不仅仅是一个简单的同类替代品。由于过去几年分选技术发生了重大变化，该分选机能够检测到比我们目前接近报废的设备更多的荧光颜色。这意味着研究人员将能够利用它进行更复杂的实验，同时跟踪许多蛋白质，并更详细地了解细胞功能和发育。分选速度也更快，可达70,000个细胞/秒。这将节省资金，因为可以在相同的时间内对更多的细胞进行分类，并且还将使数据更好，因为比较可以基于更大数量的细胞。它在分类时对细胞也更温和，这使得它适用于特别脆弱和困难的细胞类型，例如干细胞，我们血液中所有不同类型的细胞都起源于干细胞。总的来说，这是对我们现有设备的一次非常重大的升级，并开辟了许多令人兴奋的研究机会。新的分拣机将提供给任何想要使用它的研究人员，包括来自剑桥以外的研究所和大学的研究人员，以及来自公司的用户。所有用户都将支付使用机器的费用，这将有助于我们维护机器并使其保持多年的最佳运行状态。它将由一个高度熟练和经验丰富的团队管理和运行，他们已经运行CIMR流核心设施超过10年。这些杰出的科学家与研究团队密切合作，帮助他们设计和交付实验，这种协作和支持的方法使科学变得更好。大学里没有类似的机器，它的收购将使研究人员能够进行全新的实验，以了解细胞如何运作和发展的基本问题。

Humans and other complex organisms are made up of billions of individual building blocks called cells. While these cells share certain common features, they are also often highly specialised, from the neurons that make up our brain, to the red blood cells that carry oxygen from our lungs to the rest of our body, to the epithelial cells that line our intestine and absorb nutrients from the food we eat. Understanding how these cells develop such specialised functions is a fundamental question facing biological research, helping us to understand the essential rules of life itself. One technology that scientists use to understand how cells develop and function is to separate them based on certain characteristics, particularly the specialised proteins that they make, which can differ significantly from one cell type to another. Different proteins within cells can be 'tagged' using proteins or dyes with specific fluorescent colours (e.g. red, blue or green). A piece of specialised equipment known as a cell sorter can then use detectors to 'read' the amount of fluorescence each cell produces, and physically sort each cell into a different tube depending on the combination of fluorescent signals it has. In this way cell sorters can separate a complex mixture of different cell types into groups so that scientists can study each cell type separately.We are requesting funding for a new cell sorter to be housed in an already existing core facility in the Cambridge Institute for Medical Research (CIMR), where it will be accessed by researchers in CIMR, the Cambridge Stem Cell Institute and across the University of Cambridge and surrounding area. The core facility is very busy and is used by students and researchers in many of the >50 research teams in the two applying institutes. It is critical we that purchase a new sorter because our current sorting equipment is ageing and rapidly becoming obsolete, and in fact will no longer be supported by the manufacturer in two years time. However while it is essential that we obtain a replacement sorter, the specific equipment we are requesting, the Bigfoot Spectral Sorter, is much more than a simple like-for-like replacement. Because of significant changes in sorting technology in the past few years, this sorter is able to detect many more fluorescent colours than our current near end-of-life equipment. This means that researchers will be able to use it to carry out more complex experiments that track many proteins at the same time, and understand cell function and development in much greater detail. The sorting speed is also faster, up to 70,000 cells/second. This will save money as more cells can be sorted in the same amount of time, and it will also make the data even better because comparisons can be based on much larger numbers of cells. It is also gentler to the cells as it sorts, which makes it suitable for particularly fragile and difficult cell types, such as the stem cells from which all the different kinds of cells in our blood all originate. Overall, this is a very significant upgrade on our current equipment and opens up many exciting research opportunities.The new sorter will be available to any researcher who wants to use it, including those from institutes and universities outside Cambridge, as well as users from companies. All users will pay for using the machine, which will help us maintain it and keep it running optimally for many years. It will be managed and run by a highly skilled and experienced team who have been running the CIMR Flow Core Facility for >10 years. These outstanding scientists work very closely with the research teams to help them design and deliver their experiments, a collaborative and supportive approach that makes the science better. There is no similar machine within the University, and its acquisition will allow researchers to carry out completely new kinds of experiments to understand fundamental questions of how cells function and develop.