Dr Robin S. Bon

Profile

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.

Responsibilities

• Deputy Head of Department (Research & Innovation)

Research interests

We use chemical, biochemical and biophysical approaches to understand the structure, localisation, function and molecular interactions of disease-relevant proteins, and the mode-of-action of bioactive small molecules. This work supports early-stage drug discovery projects, including by CalTIC GmbH. The group works across the School of Chemistry (organic and analytical chemistry), the LIGHT laboratories (mammalian cell culture and biochemistry), and the Astbury Biostructure Laboratory (cryo-electron microscopy).

We currently focus on:

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/other proteins.

Understanding and exploiting 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 (GB) cells, but not in healthy patient-derived brain cells. In addition, the molecule also significantly reduces intracranial GB 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 GB cells. We are currently using a combination of photoaffinity labelling, mass spectrometry, cryo-electron microscopy and structure-activity relationship studies to develop a deeper understanding of the molecular interactions between mtHSPD1 and KHS101 (and its improved analogues), and to use these insights to develop new drug leads for the treatment of glioblastoma.

Qualifications

• PhD Chemistry (VU Amsterdam)
• BSc Chemistry (HU Utrecht)

Professional memberships

• Member of the Royal Society of Chemistry
• Fellow of the Higher Education Academy
• Astbury Centre for Structural Molecular Biology

Student education

I am currently a lecturer and tutor for the 1st year course 'Introduction to Medical Sciences' and topic lead for ‘Enzymes’.

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
• Cardiometabolic
• Multidisciplinary Cardiovascular Research Centre

Projects

<li><a href="//phd.leeds.ac.uk/project/174-licamm-structural-insights-into-the-modulation-of-heteromeric-trpc1/4/5-channels">LICAMM Structural insights into the modulation of heteromeric TRPC1/4/5 channels</a></li>