Biological Mass Spectrometry

Biological applications of mass spectrometry in particular have grown exponentially since the discovery of ‘soft’ ionisation techniques over 20 years ago, which has since allowed researchers to analyse much bigger molecules than was ever possible before. Combined with huge leaps in computational power, today the detailed interrogation of viruses, antibodies or proteins from cells in human and other animals in mass spectrometers is routine.

With the ability to identify, characterise and quantify proteins and other molecules present in a particular network, pathway, organelle, subcellular complex, cell or tissue – and even measure post-translational modifications – state-of-the-art mass spectrometric methods have become an essential part of any researcher’s repertoire who is interested in understanding the nature and interactions of molecules in an organism.

Yet despite significant progress, the ultimate goal of being able to monitor and analyse what is happening at the molecular level in every type of cell at every time – called functional proteomics – remains elusive. This is because functional proteomics is orders of magnitude more difficult than DNA sequencing, and today’s mass spectrometers fall far short of what is needed in terms of sensitivity, dynamic range and speed.

The ‘Biological Mass Spectrometry’ theme aims to seed a functional proteomics revolution by bringing together the UK’s world-leading technology companies and strong but currently disparate academic expertise in mass spectrometry.

The Science Directors of the theme, Professor Josephine Bunch and Professor Zoltan Takats, are consulting their communities on proposals for technologies to be developed in the mass spectrometry theme.

A key objective of the Biological Mass Spectrometry theme is to construct a unique multimodal imaging mass spectrometer instrument, which allows the molecular mapping of biological tissues at unprecedented sensitivity, chemical depth and spatial resolution. The instrument is envisioned to not only detect the building blocks of tissues, but also provide proper structural characterisation of all detected molecular species and supramolecular complexes.

Mass spectrometric imaging is a unique tool providing spatially resolved chemical information, which is particularly important for structural biology and molecular histology research. The currently available MSI approaches target different classes of molecular species at different spatial resolution and analytical sensitivity. While all of these techniques detect thousands of unknown molecular constituents, currently there is no integrated solution for their proper identification/structural elucidation.

The proposed instrument will provide comprehensive chemical information ranging from inorganic ions to multimeric supramolecular complexes at subcellular spatial resolution and will enable the swift structural identification of all species detected. The team believe that such an instrument at the crossroads of physical sciences, engineering, life sciences and biomedical research gives a perfect fit to the Franklin’s objectives.

The BMS theme, together with the other themes focusing on structural chemistry & biology, will bring along a new understanding on the compartmentalisation of molecular interaction networks. This new knowledge will stem from the untargeted co-localisation of an unprecedentedly broad range of biochemically relevant species in tissues and it will equally serve the fundamental understanding of cellular biology, pathobiochemistry and the development of new and innovative therapeutic approaches for various disease ranging from infectious diseases through dementia to cancer. Being the construction of a unique platform, this project has the potential to define the Franklin as worldwide hub for structural biochemistry.