A new mass spectrometer at University College London will soon be able to identify over 4,000 individual proteins from a single cell, a feat previously impossible with older instruments that required large, averaged samples. This matters because cells that look identical under a microscope can behave very differently—one might resist a drug while its neighbour does not. Until now, proteomics (the study of the proteins that actually carry out a cell’s functions) has mostly measured bulk populations, masking these crucial differences. The new instrument fills the final gap in UCL’s single-cell workflow, combining advanced sample preparation and deep-learning bioinformatics with the sensitivity needed to analyse individual cells. If successful, this capability will allow researchers to map protein interactions and modifications at unprecedented resolution. This could transform understanding of how cells compete, how DNA repairs itself, and how the immune system adapts—areas directly relevant to industrial biotechnology and drug development. The instrument will be open to academic and industrial users across the UK and beyond, and the facility will train a new generation of scientists in this technology. While the research is fundamental, similar advances in single-cell genomics have already reshaped medicine; single-cell proteomics could do the same for how we understand and treat disease at the molecular level.
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Mass spectrometry (MS)-based proteomics has revolutionised cell biology by enabling the identification of tens of thousands of proteins per cell, and the detailed characterisation of post-translational modifications (PTMs). Traditionally, these analyses needed large quantities of protein, which led to bulk and average readouts that obscured important differences between individual cells. Single-cell technologies on the contrary now allow for the study of cellular heterogeneity and protein dynamics at an unprecedented resolution. Recent advancements in sample preparation and mass spectrometry instrumentation have made single-cell proteomics feasible. It is now possible to reproducibly identify over 4,000 proteins from single-cells, and significantly improve the depth of coverage for crosslinking experiments, enhancing our understanding of protein-protein interactions (PPIs) and cellular functions. These capabilities are crucial for studying complex biological systems, as proteins carry out essential cellular functions and their interactions influence cellular behaviour. We request funds to purchase the latest and most sensitive mass spectrometer, capable of such single-cell measurements. The new mass spectrometer will be placed in the UCL Mass Spectrometry Science Technology Platform (MS-STP), ensuring broad community access and supporting diverse research initiatives. The MS-STP has a growing demand for single-cell proteomics, which will provide deeper insights into cellular heterogeneity and function. Since its establishment in 2019, UCL has heavily invested in the MS-STP, including ancillary instrumentation for isolating and processing single-cells for downstream MS analyses, as well as the latest deep-learning-enabled bioinformatics tools for processing MS data. The only missing component for a complete single-cell proteomics workflow is a single-cell capable mass spectrometer. The proposed equipment will advance research aligned with BBSRC's strategic goals in areas such as industrial biotechnology, adaptive immunity, DNA repair mechanisms, proteostasis and cell competition, to name a few. Given the limited availability of such advanced instruments in the UK, UCL is positioned to lead in this field, driving innovation and impact in biosciences. The MS-STP facility is accessible not only to researchers at UCL but also to those from institutions outside UCL and even outside the UK. This broad accessibility has attracted a diverse range of users, including those from industry. The facility offers comprehensive training programs for users, enabling them to operate mass spectrometers and stay updated with the latest advancements in MS technology. This training ensures that users can effectively utilise the equipment for their research, fostering a collaborative and innovative environment and providing highly skilled personnel in this exciting new technology for the benefit of the UK economy.
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