High dimensional spectral flow cytometry for immunology, cell biology, and infectious diseases research

The University of Dundee is a leading centre for research in the study of living organisms and developing knowledge and innovations in the treatment of disease, to address health problems affecting people across the globe. Integral to research undertaken in Dundee is access to cutting edge technology and expertise. One such technology is called flow cytometry. A flow cytometer uses lasers to detect cells and quantify components which are either on the surface or inside the cell (e.g., DNA, proteins, lipids). Cells in suspension flow through the flow cytometer where they pass one-by-one through lasers, at a rate of thousands of cells per second. As a cell passes through the lasers, it generates light signals which are detected and quantified, which tells us how much of the component of interest is present. Existing technology is limited to the number of cell components it can detect (up to 18) and is unable to distinguish small particles, such as small bacteria or viruses. A 'spectral' flow cytometer allows more than 35 different components to be detected in a single sample and allows small cells and particles to be evaluated. A spectral flow cytometer gives vast improvements over existing technology in the depth of sample analysis, giving new insights into how cells function. This technology will support research in diverse areas of biology, to give a better understanding of the causes of disease and to support the development of new interventions or treatments.
One key objective of the research in Dundee is to improve understanding of the cellular mechanisms causing neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Another area of research looks at how to control cell proliferation with the aim to understand how to prevent the abnormal growth and proliferation of cancer cells. One other objective of the research in Dundee is to develop new treatments for infectious diseases caused by a variety of different agents, such as viruses (e.g., Covid-19), bacteria (e.g., Streptococcus), and parasites (e.g., malaria). The vision is to understand how these organisms function and resist drug treatments. The immune system plays an important role in fighting and protecting us from these infectious agents, but it can also have a negative effect on health when it mistakenly attacks our own cells (e.g., asthma, rheumatoid arthritis). A significant amount of research is looking at how our immune system is regulated and how we can maintain it as being our 'friend' rather than 'foe'. In all cases, the aim of the research is to translate the findings from discovery science into the development of new drugs or improvements in current treatment strategies.

This proposal requests funds for a spectral flow cytometer to support furtherance of MRC-remit, high-impact research at University of Dundee. A spectral flow cytometer is a laser based single-cell technology commonly used in life sciences and medical research. It is a powerful tool for the quantification of cellular components and is particularly useful for identifying and quantifying rare cell types in heterogenous populations. Cellular components, such as intracellular and extracellular proteins, are labelled with specific fluorochromes, which are in turn detected and quantified. In this way, thousands of individual cells per second can be analysed for >35 different fluorochromes. This facilitates an in-depth analysis of the biology and resolution of sample heterogeneity, far superior to that of the existing technology available, which is limited to 18 fluorochromes. Other benefits are improved resolution for detecting small particles (80nm compared to 500nm for existing instrumentation), increased capacity, and higher sensitivity, which will improve data reproducibility and robustness. These technological innovations will be transformative for the rapid advancement of many medical and biological research projects in Life Sciences in Dundee. The key objectives of the research are to make fundamental discoveries in the molecular and cellular mechanisms involved in the development and prevention of diseases, and to translate these discoveries to address national and global health challenges. There is a strong focus on research in cell signalling, immunology, parasitology, microbiology, neurodegeneration, and inflammation plus a strong translational program in drug discovery for infectious diseases. Integral to the success of this research are state-of-the-art technologies, like spectral flow cytometry, which allow researchers to make innovative discoveries to help in our understanding of health and disease.