Prof David Clarke

Chair of Mass Spectrometry

Research summary

Mass Spectrometry, Protein Chemistry, Chemical Biology, Biomolecular Interactions. 

Current research interests

My research is focused on developing new techniques in the field of mass spectrometry and applying these new methodologies to increase our understanding of complex biomolecules and biological systems. These findings have impacts in a range of fields including providing sustainable routes for manufacturing using biocatalysts, helping us understand disease pathways and providing new tools for the drug discovery process.   By using chemical biology techniques and applying our chemical understanding we are creating new strategies that increase the capability of mass spectrometry. Since 2019, my research group has established the technique of isotope-depletion mass spectrometry (ID-MS). This strategy significantly increases the analytical sensitivity (up to 5-fold) when studying intact proteins; allowing us to gain a more detailed understanding of protein structure and analyse larger and more complex protein systems. Our new strategies are being integrated in several research studies with industrial partners in a range of fields including: instrument development (Thermo Fisher), vaccine design (GSK Vaccines), drug discovery (AstraZeneca) and synthetic biology (Ingenza).

  1. A native mass spectrometry approach to qualitatively elucidate interfacial epitopes of transient protein–protein interactions, CGL Veale, A Chakraborty, R Mhlanga, F Albericio, BG de la Torre, A. L. Edkins, D. J. Clarke. Chem. Commun., 2024, 60 (45), 5844-5847.
  2. Visualizing the interface of biotin and fatty acid biosynthesis through SuFEx probes. A. Chena, Rea, T. Davisa, K. Trana, G. Louieb, M. Bowmanb, D.J. Clarke, C. Mackay, D. Campopiano, J. Noel, and M. Burkart.  J. Am. Chem. Soc. 2024. 146 (2), 1388-1395
  3. Determining the Location of the Alpha-Synuclein Dimer Interface using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry. K. Jeacock, A. Chappard, K. Gallagher, C. Mackay, D. Kilgour, M. Horrocks, T. Kunath, D.J. Clarke. J. Am. Soc. Mass Spec. 2023. 34, 5, 847–856.
  4.  Pore dynamics and asymmetric cargo loading in an encapsulin nanocompartment revealed by Cryo-EM and hydrogen/deuterium exchange mass spectrometry. J. Ross, Z McIver, T.  Lambert, C. Piergentili, K. Gallagher, J. Bird, F.  Cruickshank, E. Zarazúa-Arvizu, L. Horsfall, K. Waldron, M. Wilson, C. Mackay, A. Baslé, D.J. Clarke#, J. Marles-Wright#.  Science Advances, 2022, 8 (4), eabj4461
  5.  Isotope Depletion Mass Spectrometry (ID-MS) for Accurate Mass Determination and Improved Top-Down Sequence Coverage of Intact Proteins. K. Gallagher, M. Palasser, S. Hughes, C. Mackay, D. Kilgour, D.J. Clarke. Journal of the American Society for Mass Spectrometry, 2020, 31 (3), 700-710.

For a full list of publications please see Google Scholar.  https://scholar.google.com/citations?user=Net2FBIAAAAJ&hl=en

 

Expertise: mass spectrometry, analytical chemistry, protein characterisation, biomolecular analysis.

Sectors: Analysis, Biotechnology, Healthcare, Food & Drink, Drug Discovery & Development

Prof. Clarke is the Chair of Mass Spectrometry at the University of Edinburgh and has over 20 years’ experience in using mass spectrometry and related techniques for the molecular characterisation of complex chemical and biological systems. Over the last decade we have worked with industry partners from a range of sectors including Pharma (characterisation of biologics – vaccines and antibody-drug conjugates), Agri-Tech and the Food and Drink Sector (molecular characterisation of environmental samples), and the Energy Sector (analysis of novel fuel formulations). Prof. Clarke is also the academic lead for the School’s Mass Spectrometry Facility.

Find out more:

Clarke Lab website

School of Chemistry Mass Spectrometry Facilities

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