Introduction

Mass spectrometry – a century-old technique that ionises a sample to measure the combined masses of its atoms – has established itself as a tool to test food and environmental contamination, perform carbon dating, confirm drug abuse and tackle a host of other tasks.

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.

Seeding a functional proteomics revolution

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.

To be added to the mailing list for Biological Mass spectrometry and receive theme related updates, please e-mail info@rfi.ac.uk.

 

Professor Josephine Bunch

Science Co-Director Biological Mass Spectrometry

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Theme Leader

Professor Josephine Bunch

Science Co-Director Biological Mass Spectrometry

Professor Josephine Bunch is Co-Director of the National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI) at NPL and Chair of Biomolecular Mass Spectrometry at Imperial College London. Josephine is an NPL Fellow and leads research and metrology in MALDI […]

Professor Zoltan Takats

Science Co-Director Biological Mass Spectrometry

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Theme Leader

Professor Zoltan Takats

Science Co-Director Biological Mass Spectrometry

Professor Takats has obtained his PhD from Eötvös Loránd University, Budapest, Hungary. He has worked as a post-doctoral research associate at Purdue University, Indiana, USA. After returning to Hungary, he served as Director of Cell Screen Research Centre and also […]

Microscope mode MSI

This instrument will allow for ultrafast, high throughput mass spectrometry imaging. Unlike standard probe-based sampling approaches, this offers vast improvements in imaging throughput. This novel instrument is a stigmatic mode (microscope mode) TOF SIMS imaging instrument and has the potential to provide rapid imaging of the many chemical constituents present at a surface. However, the requirement for a detection system that can acquire large numbers of images with nanosecond resolution on a timescale of tens to hundreds of microseconds has proved to be a significant bottleneck in the development of the technique.

Project details

High resolution MSI

A novel Secondary Ion Mass Spectrometry (SIMS) instrument will be constructed to include a water cluster ion source and laser post-ionisation. Gas cluster and water cluster ion beams will be used to reduce and control fragmentation during surface sampling and ionization. To boost sensitivity for selected analyte classes, laser post-ionisation strategies will be assessed.

Project details

Hybrid Imaging Instrument

This Hybrid Imaging instrument aims to make it possible for high-mass resolution measurements  to be conducted in a spatially resolved manner. The instrument combines a novel mass analyser configuration with capabilities for ion fragmentation methods with a novel collection of ion sources, which are designed for generation of singly and multiply charged ions. This, coupled with post-ionisation, will allow for greater sensitivity, broader analyte coverage and enhanced structural characterisation experiments.

Project details