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

 

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