A new mass spectrometer at the University of Birmingham will pick out and analyse individual proteins from complex mixtures of hundreds, even when those proteins are present in vanishingly small amounts. Proteins are the molecular machines that run every cell, but many critical ones are rare and easily lost among more abundant neighbours. Current instruments often miss these low-abundance proteins, whose misregulation can derail cellular function. This machine uses a high-mass quadrupole to isolate them in real time, then applies multiple fragmentation techniques to identify each protein with certainty. The impact is fundamental. Researchers across the Midlands—from the Universities of Birmingham, Warwick, and Leicester—will use the instrument to tackle BBSRC strategic priorities: understanding the rules of life, developing transformative technologies, and applying bioscience to sustainable agriculture and health. By revealing how newly discovered proteins move and interact with partners, the work could eventually underpin advances in crop resilience, disease detection, or biomanufacturing. For now, it is curiosity-driven science that builds the infrastructure for future breakthroughs—much as early protein analysis tools once enabled today’s precision medicine.
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Proteins are intricate and extensively modified molecules that engage in the formation of loosely-bound complexes with themselves and other biomolecules. Functioning as biological machines, proteins orchestrate the vital processes essential for life, with their roles intricately tied to both their composition and overall structure. Mass spectrometry is an analytical technique which enables us to dive into the workings of proteins, offering a deeper understanding of their functionalities. This proposal will install the most advanced mass spectrometer for structural biology at the University of Birmingham. This state-of-the-art instrument has the capability to unravel the characteristics of newly identified proteins, shedding light on their coordinated movements with partnering molecules. Equipped with a high mass quadrupole, the mass spectrometer boasts the ability to analyse a diverse variety of large proteins and protein complexes in real time. Crucially, this quadrupole enables low-abundant yet critical proteins, whose misregulation can lead to significant alterations in cellular function, to be isolated in-turn and picked out for analysis from within complex mixtures of hundreds of proteins. In addition, the mass spectrometer will be equipped with a variety of fragmentation techniques that will enable each protein to be characterised with certainty, adding a high level of precision for accurate identification and protein function assignment. By uniting a broad range of researchers from the University of Birmingham and the Midlands region (University of Warwick, University of Leicester) whose research interests span diverse disciplines, the proposal will apply this state-of-the-art technology to unlock our capabilities to resolve key challenges within key strategic priorities that have been outlined by the BBSRC; understanding the rules of life, transformative technologies, bioscience for sustainable agriculture and food, and biosciences for an integrated understanding of health.
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