Mass spectrometry based structural proteomics

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One of the major challenges in biological science is to capitalise on the wealth of genomic information arising from DNA sequencing and characterise the structure and dynamics of the encoded proteins. However, while genome sequencing has become very rapid, no methods currently exist which can experimentally determine the molecular details of the gene-products on a comparable timescale. As such the gulf between our understanding of what proteins are present in an organism, how they orchestrate the cellular processes necessary to life, and their malfunction in disease is ever increasing.Mass spectrometry (MS) is a traditional physical chemistry approach that has revolutionised the experimental identification of proteins and quantification of their cellular abundances. The success of such MS-based 'proteomics' is underpinned by the robust automation of both data acquisition and analysis. Far from being limited to identifying proteins, MS has recently emerged as an exciting technique for characterising the molecular details of the cellular machines they assemble into. This novel application of MS has allowed the experimental elucidation of the stoichiometry, architecture, and dynamics of protein assemblies. We propose to bridge the technological gap between these two fields of proteomics and structural biology by developing data analysis software to enable the high-throughput characterisation of protein assemblies by means of MS.