A new mass spectrometer will allow UK researchers to map the complex sugar molecules that coat the surface of every cell in the body. These sugar structures—called glycans—are the most abundant and diverse biomolecules on Earth, yet they remain poorly understood compared to proteins and DNA. They sit on the cell’s outer surface, where they act as the primary interface with the outside world, mediating how cells recognise each other. This recognition underpins everything from immune responses to viral infection. The problem is that existing mass spectrometers at Imperial College, the Quadram Institute, and other partner sites are ageing, unreliable, or absent altogether. The new Bruker neofleX MALDI instrument will replace and supplement this failing equipment, enabling researchers to determine the detailed structure of glycoproteins, glycolipids, and other biomolecules. If successful, the instrument will accelerate the development of new medicines, antibiotics, vaccines, and diagnostics for both humans and animals. It will also help characterise emerging viruses to assess their pandemic potential, and speed up the production of microbial food proteins for sustainable agriculture. The instrument will be open-access to academic and industrial users, supporting over £26 million of current BBSRC-funded research.
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Biological life is only possible because of its inherent biomolecular building blocks such as sugars, lipids and proteins. In order to understand the myriad of biological functions that these biomolecules undertake we need to be able to characterise their detailed structure. A particular emphasis will be placed on sugars, sometimes also referred to as glycans or carbohydrates, in the form of polysaccharides or glycoconjugates (bound to proteins and lipids), as they are the most abundant and structurally diverse class of biomolecules on the planet. Glycosylation is also the most important protein modification in terms of the number of proteins modified and the functional diversity it generates, which directly impacts on their stability and half-lives. Glycoproteins, glycolipids and glycan-binding proteins, which specifically recognize particular glycan structures, are located on the cell's surface. As this is the cells primary interface with the external environment, many biologically significant events can be linked to specific glycan recognition between cells. The structural characterisation of biomolecules requires the development and exploitation of high sensitivity analytical methods. Mass spectrometry is such an analytical method that is particularly well suited to characterize biomolecules. A mass spectrometer provides two important pieces of information about a biomolecule, or a portion of a biomolecule: its mass and its charge. This key information can be used to derive the detailed structure of the biomolecules which is vital for working out their function. In this application we propose to purchase a state of the art high performance Bruker neofleX MALDI mass spectrometer that is particularly well suited to allow the characterisation of biomolecular structures. The applicant team from Imperial, the Francis Crick Institute, the Quadram Institute, the Pirbright Institute and the Animal and Plant Health Agency, are world leading scientists supported by >£26M of relevant current BBSRC-funded research and >£6M of relevant UKRI-funding, whose research is underpinned by structural data generated by MALDI-MS instrumentation. This is being held back by aging and increasingly unreliable current MALDI instrumentation at Imperial and the Quadram, and lack of such instrumentation at the Francis Crick Institute, the Pirbright Institute and the Animal and Plant Health Agency. Because of the diverse research activities of the applicant team the new instrumentation will be used to address some of the most important biomolecular structural research challenges within the UKRI-BBSRC strategic research priorities such as understanding the rules of life, transformative technologies, bioscience for sustainable agriculture and food, bioscience for renewable resources and clean growth and bioscience for an integrated understanding of health. It will advance the development of new medicines, antibiotics, vaccines and diagnostics to tackle disease in both humans and animals thereby improving health, enhancing sustainable health and food production and protecting biodiversity, it will allow the characterisation of emerging viruses to facilitate the assessment of their pandemic potential, and it will accelerate the production of microbial food proteins to enhance sustainability. The Bruker neofleX MALDI will be integrated into the existing Centre for Integrative Systems Biology and Bioinformatics (CISBIO) Mass Spectrometry facility at Imperial. It will therefore be made open–access to all members of Imperial and the broader academic and industrial research community. The Imperial funded facility manager will interact closely with Bruker to ensure efficient and timely installation of the neofleX and will receive detailed training which he will subsequently pass on to new instrument users.
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