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Our group works in the field of chemical biology, applying chemical tools to ask questions about dynamic protein function and small molecule mode of action in live cells and at the molecular level. We work closely with scientists from other disciplines, enabling us to design innovative tools for cell biology and to tackle a wide range of biological questions - from the mechanisms of antibacterial resistance, to how plants regulate growth, and how cancer cell signalling pathways can be perturbed.

Our interests include:

  • small molecule mode of action / target identification
  • cell-cell communication e.g. quorum sensing, interkingdom signalling
  • protein post-translational modifications
  • protein-protein interactions
  • bioorthogonal ligation chemistry
  • activity-based protein profiling
  • photoaffinity labelling
  • mass spectrometry-based proteomics

Target identification methodology and discovery of chemical probes. We are developing chemical probes with photo- or chemically-reactive functionalities to stabilise their interactions with protein targets in live cells. We also equip probes with small, minimally disruptive tags, that then act as handles for selective labelling of probe-protein complexes via click chemistry. Click chemistry is very versatile and we can attach fluorophores to visualise proteins, or affinity tags to isolate and identify them by mass spectrometry proteomics. We are also interested in more efficient ways to discover chemical probes. Projects: mode of action of plant pathogen fungicides, with Syngenta; high-throughput approaches to chemical probe discovery, with Adam Nelson.

Protein modification. Proteins are widely modified with small molecules, exerting exquisite and rapid control over protein function. Two examples are protein lipidation, which often mediates protein localisation to membranes, and redox modification of cysteines (with Prof Alison Baker  and Prof Christine Foyer). We are interested in developing small molecule probes to mimic or profile these modifications to explore their roles in different biological contexts and with spatio-temporal control.

Protein interactions. We are interested in understanding and modulating protein-protein interactions in vitro and in living systems. In collaboration with Dr Anton Calabrese we are using chemical tools to understand protein structure and interactions using advanced mass spectrometry approaches. As part of the BBSRC sLoLa SPIDR we are developing tools to profile, inhibit and modulate protein interactions of the mitotic kinase Aurora A - with Prof Andrew Wilson (Birmingham), Prof. Richard Bayliss, Dr Darren Tomlinson, Prof Sheena Radford, Dr Takashi Ochi, Prof Colin Johnson (Leeds) and Prof Fanni Gergely (Oxford).

Cell-cell signalling. We are interested in exploring native small molecule-protein interactions in complex, multispecies biological systems. For example, there is increasing evidence that bacterial and human cells eavesdrop on each other’s cell-cell communications, yet in many cases we do not know how signals are sensed or we lack the tools to understand the mechanisms of sensing.

We are members of the Astbury Centre for Structural Molecular Biology and of Leeds Omics.

Current funding

  • BBSRC sLoLa Grant Deciphering the function of intrinsically disordered protein regions in a cellular context (2021-25). A. Wilson (PI), D. Tomlinson, S. Radford, F. Gergely, M. Wright, R. Bayliss, T. Ochi, C. Johnson
  • Leverhulme Trust Research Grant Do redox modulated PTMs lead to catalase moonlighting? (2021-25) A. Baker (PI), M. Wright, C. Foyer
  • EPSRC Strategic Equipment Grant A Platform for Chemical Probe Identification and Optimization Facilitating Interrogation of Biological Mechanisms (2021-23). A. Wilson (PI), A. Calabrese, F. Sobott, S. Warriner, M. Wright.
  • EPSRC International Centre to Centre Grant Autonomous Phenotype-Directed Molecular Discovery (2021-24). A Nelson (PI), Basham (RFI), Marsden, Wilson, M. Wright, (Leeds), Waldmann (MPI-Dortmund)

Recent funding

  • Leverhulme Trust Phenotype-directed emergence of unnatural products (2018-22), with Adam Nelson (Leeds) and Terry Smith (St Andrews)
  • EPSRC New Investigator Award Chemical probes to decode the subcellular redox proteome (2019-22). M. Wright (PI)
  • Wellcome Trust Mass spectrometry infrastructure underpinning research into the molecular basis and biological mechanisms in health and disease (2017-21), led by Frank Sobott