Activity based probes, which mimic an enzyme substrate or protein binding partner but contain a chemical trap, are powerful tools in biological research. Such probes have been employed widely for both basic research and guiding drug discovery efforts. They are used to discover and characterise novel enzymatic activities, inhibitors, biomarkers and cellular localisation.

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The advantages of a “chemical proteomics” approach using activity-based probes over biochemical assays lie in the fact that they allow the selective study of enzymes in their native environment. Alterations with cell type and disease state and have a huge impact on protein function and selectivity, an activity based profiling approach will be sensitive to these factors while still maintaining a highly specific readout, affording the best of both worlds between biochemical and phenotypic assays.

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​Research in the laboratory focuses on the synthesis of new activity based probes for chemical biology and molecular physiology applications. Current research focuses on DNA damage repair and deubiquitinating enzymes (DUBs) as two key regulatory classes of enzyme.

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There is growing evidence for a pivotal role of DUBs in pathologies including infection, autoimmunity, cancer and neurodegeneration. DNA damage repair enzymes play crucial roles in cell maintenance and response to cancer treatments.

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​Techniques to make the probes range from protein expression and modification to right through to purely synthetic approaches. An activity based proteomics approach allows us to study these key enzymes in their native environment, examining how activity levels change with cellular state.