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

点击翻译按钮获取中文摘要

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.