Advancing the Frontiers of Mass Spectrometry for Precision Immunology

Modern immunology increasingly depends on our ability to measure tiny amounts of biological material with exceptional sensitivity. In cancer and immune disease, important signals may exist only in small biopsies, rare cell populations or very low-abundance peptides that conventional mass spectrometry fails to detect. This PhD project asks: how far can we push mass spectrometry to reveal biology that is currently invisible? The student will develop next-generation mass spectrometry, proteomics and immunopeptidomics technologies to improve sensitivity, depth and confidence in the analysis of limited clinical samples. The project may involve advances in sample preparation, chromatography, fragmentation, data-independent acquisition, targeted mass spectrometry, automation and computational analysis. A major focus will be immunopeptidomics, where HLA-bound peptides are often present at extremely low abundance. New approaches will be developed to identify antigens missed by conventional workflows, including cryptic, non-canonical and non-classical HLA-associated peptides. The project will also explore ultra-low-input and spatial immunopeptidomics, with the goal of analysing microscopic tumour regions, needle biopsies, rare cell populations and other samples currently considered too small for comprehensive analysis. Working with industry A distinctive feature of this project is our close collaboration with mass spectrometry technology developers and biotechnology companies. The student will have opportunities to evaluate emerging technologies, contribute to method development and benchmarking, interact directly with industry scientists and, where available, work with early-access technologies. This provides valuable exposure to how new analytical technologies move from instrument development to biological and clinical applications, while opening career pathways across academia, biotechnology and the mass spectrometry industry. What will the student learn? The student will gain advanced training in mass spectrometry, proteomics, immunopeptidomics and analytical technology development. They will develop expertise in high-resolution tandem mass spectrometry, fragmentation, data-independent acquisition, targeted proteomics, low-input workflows, automation, bioinformatics and machine-learning-assisted data analysis. Importantly, new technologies will be applied directly to clinically relevant questions in cancer immunology and precision medicine. The broader vision is to redefine what can be measured by mass spectrometry and develop technologies that enable discoveries from samples that are currently too small, too complex or too difficult to analyse.