STRUCTURAL PROTEOMICS

Biological mechanisms rely on biomolecules adopting transient ‘excited’ states, and forming ephemeral, sometimes heterogeneous, assemblies. Structural characterisation of these functionally important species in time and space remains a key challenge that requires the development of new methodologies.

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Our research focuses on the development and application of structural mass spectrometry (MS) methods, including:

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• Native MS

• Ion mobility (IM)

• Chemical crosslinking

• Hydrogen-deuterium exchange [HX-MS]

• Fast photochemical oxidation of proteins [FPOP].

We aim to use an integrated approach, combining data from multiple MS techniques, along with data from complementary biophysical and computational tools to reveal new mechanistic insights about dynamic proteins and their assemblies.

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One of the key challenges in structural biology is to elucidate how the dynamic interactome mediates biological function in the crowded cellular milieu. Recently, structural MS methods have been shown to be promising tools to achieve this endeavour, including XL-MS and in-cell FPOP, yielding unprecedented insights into the structure and organisation of cellular macromolecular assemblies. We aim to develop optimised XL-MS and FPOP workflows, exploiting the full potential of these techniques to elucidate the molecular composition and architecture of protein assemblies directly in cells.