Dr Robin S. Bon
- Position: Associate Professor of Chemical Biology
- Areas of expertise: chemical biology; ion channels; organic chemistry; pharmacology; photoaffinity labelling; protein labelling; bioorthogonal chemistry; surface chemistry
- Email: R.Bon@leeds.ac.uk
- Phone: +44(0)113 343 0785
- Location: 7.04 LIGHT Laboratories
- Website: Astbury Centre profile | Twitter | LinkedIn | ORCID
I joined the University of Leeds in 2009 as a Senior Research Fellow in the School of Chemistry, where I established a new research group and contributed to taught courses on all levels. In 2015, I was appointed as Lecturer in Cardiovascular Chemistry in the School of Medicine, and promoted to Associate Professor of Chemical Biology in 2019.
I obtained my PhD in Chemistry (2007) from the Vrije Universiteit Amsterdam, where I worked on novel isocyanide-based multicomponent reactions for the exploration of chemical space. Between August 2006 and October 2009, I worked as a MPI/Alexander von Humboldt Postdoctoral Fellow at the Max Planck Institute of Molecular Physiology in Dortmund, where I developed chemical tools to study protein lipidation.
- LICAMM Action Group Lead for Cross-Faculty Collaborations
- Secretary of the Chemical Biology and Bioorganic Group of the Royal Society of Chemistry
We use chemical, biochemical and biophysical approaches to understand the molecular mechanisms underlying (cardiovascular) health/disease and the effects of bioactive small molecules. The group has lab space in the School of Chemistry (organic and analytical chemistry) and in the LIGHT laboratories (mammalian cell culture and biochemistry).
Recent and current projects include:
Structural insight into modulation of TRPC1/4/5 channels
Transient Receptor Potential (TRP) proteins, which include the TRPM, TRPV, TRPA and TRPC subtypes, form tetrameric, non-selective cation channels permeable by Na+and Ca2+. For all 28 mammalian TRP proteins, four monomers are needed to form a functional ion channel, and channels may consist of homomers or heteromers of subunits, each with their own characteristics and functions. This project focuses on homomeric and heteromeric channels formed by TRPC1, TRPC4 and TRPC5. Their implication in various human disease states has led these channels to emerge as potential therapeutic targets. However, little is known about the exact composition of TRPC1/4/5 tetramers in different tissues, and the lack of information about binding modes of channel modulators prevents the design of tetramer-specific activators and inhibitors. In this project, we use molecular biology, photoaffinity probes, mass spectrometry and cryo-electron microscopy to unravel the interactions between specific TRPC1/4/5 subunits, between TRPC1/4/5 channels and small-molecule modulators, and between TRPC1/4/5 channels and lipids.
(Former) PhD students and postdocs involved (funder): Aisling Minard (BBSRC/AstraZeneca), Isabelle Pickles (Wellcome Trust), Dr Claudia Bauer (BBSRC), Dr David Wright (BBSRC). In October 2018, Aisling started her postdoc at Imperial College.
Main collaborators: Prof. David Beech (Leeds Institute of Cardiovascular and Metabolic Medicine), Dr Stephen Muench (School of Biomedical Sciences), Prof. Frank Sobott (School of Molecular and Cellular Biology), Dr Megan Wright and Dr Stuart Warriner (both School of Chemistry), Prof. Mathias Christmann (Freie Universität Berlin, Germany), Prof. Katsuhiko Muraki (Aichi Gakuin University, Kusumoto, Japan).
Novel ionisation enhancers for mass spectrometry of biological samples
Label-assisted laser desorption/ionisation mass spectrometry (LALDI-MS) is a novel and powerful tool for the selective analysis of labelled species by mass spectrometry. LALDI-MS is carried out in a similar manner to matrix-assisted laser desorption/ionisation mass spectroscopy (MALDI-MS), however, the external matrix component of MALDI has been replaced with a laser desorption/ionisation-enhancing label. Through this development, LALDI-MS has gained several benefits over MALDI-MS, eradicating concerns over optimum analyte–matrix pairings and allowing analysis to be performed directly against a complex background without the need for purification. We develop novel, water-soluble, LALDI tags for in situ labelling of analytes in complex samples. The technology allows us to directly analyse biological samples without the need for purification.
PhD student involved (funder): Jacob Hauser (University Research Scholarship). In November 2019, Jake started as a JSPS Postdoctoral Fellow at Kyoto University.
Main collaborators: Prof. Jane Thomas-Oates (Centre of Excellence in Mass Spectrometry, University of York), Dr Stuart Warriner and Dr Robert Menzel (both School of Chemistry)
Understanding the mode-of-action of a bioactive small molecule
The small molecule KHS101 induces a catastrophic metabolic phenotype – leading to lethal cellular degradation – in a range of patient-derived glioblastoma multiforme (GBM) cells, but not in healthy patient-derived brain cells. In addition, the molecule also significantly reduces intracranial GBM xenograft tumour growth upon systemic administration, without discernible side effects. Through a major interdisciplinary collaboration that involved chemical proteomics, global proteomics, transcriptomics, metabolomics, and assays in vitro, in cells and in animal tissues, the mitochondrial chaperonin HSPD1 was identified and validated as the relevant target of KHS101 in GBM cells. We are currently using a combination of photoaffinity labelling, mass spectrometry and cryo-electron microscopy to develop a deeper understanding of the molecular interactions between mtHSPD1 and KHS101.
(Former) PhD students involved (funder): Dr Hester Beard (EPSRC DTA), David Klebl (Wellcome Trust). In June 2018, Hester started as a postdoc at KU Leuven (Belgium)
Main collaborators: Dr Heiko Wurdak (Leeds Institute of Cancer & Pathology), Dr Lee Roberts (Leeds Institute of Cardiovascular and Metabolic Medicine), Prof. Neil Ranson, Dr Emma Hesketh and Prof. Frank Sobott (all School of Molecular and Cellular Biology), Dr Stephen Muench (School of Biomedical Sciences), Dr Shoutian Zhu (formerly California Institute for Biomedical Research), Prof. Jason Gestwicki (UCSF)
Catalytic tag transfer reagents for traceless protein labelling
Protein-protein interactions (PPIs) mediate a large number of important processes within the human body. As such, their study is of huge importance in the understanding of diseases and the development of pharmaceuticals. In order to elucidate the structure and function of specific proteins, it is important that they can be studied within their native cellular environment. The aim of this project is to develop a set of modular chemical tools to study protein-protein interactions (PPIs) formed by endogenous proteins, ultimately applicable for use in cellular studies. So far, we have developed tag transfer reagents consisting of a protein ligand linked to a transition metal catalysts, which allow selective, traceless, light-induced protein labelling with sub-stoichiometric amounts of reagent.
Former PhD student involved (funder): Dr Hester Beard (EPSRC DTA). In June 2018, Hester started as a postdoc at KU Leuven (Belgium)
Main collaborators: Prof. Andrew Wilson (School of Chemistry), Dr Andrew Macdonald (School of Molecular and Cellular Biology)
- PhD Chemistry (VU Amsterdam)
- BSc Chemistry (HU Utrecht)
- Member of the Royal Society of Chemistry
- Fellow of the Higher Education Academy
- Astbury Centre for Structural Molecular Biology
- Multidisciplinary Cardiovascular Research Centre
I am currently a lecturer and tutor for the 1st year course 'Introduction to Medical Sciences' and topic lead for ‘Enzymes’. In addition, for the Foundation Year of Leeds' Wellcome Trust 4-year PhD programme, I lecture on 'Chemical Protein Labelling in Cells' and 'An Introduction to Ion Channels and Ion Channel Drug Discovery' and am a co-lead for the module 'Membranes and Membrane Proteins' on this programme.
My previous teaching experience in Chemistry, Biology and Medicine includes the development and delivery of new lecture courses ('Revision Course in Organic Chemistry', ''Strategy in Synthesis of Complex Molecules', 'Chemical Approaches to Protein Labelling', 'Chemical Probes for Biological Research', 'Ion Channel Drug Discovery'), academic and personal tutoring, development and supervision of laboratory courses/projects, and mentoring and assessment of students on industrial placement.
I have attained professional recognition for my teaching and learning support through a Fellowship of the Higher Education Academy.
Research groups and institutes
- Leeds Institute of Cardiovascular and Metabolic Medicine
- Discovery and Translational Science
<li><a href="//phd.leeds.ac.uk/project/423-direct-characterisation-of-trpc-channel-dynamics-triggered-by-drug-like-modulators-using-high-speed-atomic-force-microscopy">Direct characterisation of TRPC channel dynamics triggered by drug-like modulators using high-speed atomic force microscopy</a></li>
<li><a href="//phd.leeds.ac.uk/project/569-mrc-dimen-doctoral-training-partnership:-understanding-zinc-dependent-regulation-of-trpc5-channels-and-its-role-in-diabetes">MRC DiMeN Doctoral Training Partnership: Understanding zinc-dependent regulation of TRPC5 channels and its role in diabetes</a></li>
<li><a href="//phd.leeds.ac.uk/project/174-structural-insights-into-the-pharmacological-modulation-of-cardiovascular-ion-channels.">Structural insights into the pharmacological modulation of cardiovascular ion channels.</a></li>