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Darragh O'Brien
Ph.D.
Head of Structural & Mechanistic Proteomics
Senior Researcher in Translational Proteomics & Neurodegenerative Disease | Research Fellow - Green Templeton College
Biosketch
Darragh O’Brien is a senior researcher in Translational Proteomics at the Nuffield Department of Medicine, University of Oxford, where he utilises biological mass spectrometry (MS) approaches to characterise and decipher mechanisms of human disease. His interests lie in how protein intrinsic disorder and post-translational modifications such as phosphorylation and ubiquitination contribute to protein function and disease, with a focus on neurodegeneration and dementia, specifically the tauopathies Alzheimer's Disease (AD) and Progressive Supranuclear Palsy (PSP). Before joining Oxford, Dr O’Brien spent several years as a researcher at Institut Pasteur in Paris, where he used integrative structural biology workflows to study the protein conformational dynamics of macromolecular systems. Post-doctoral work at University College London and PhD studies in Neuroscience at the Institute of Psychiatry, King’s College London further advanced his expertise. During his PhD, which was supervised by Professor Sir Simon Lovestone, he developed neuroproteomic strategies for AD biomarker discovery and validation in human plasma and cerebrospinal fluid. Dr O’Brien’s scientific journey began with an Honors Degree in Biochemistry from University College Dublin in 2004, where his undergraduate thesis explored mechanisms of amyloid processing in AD, under the guidance of Professor Dominic Walsh. Between 2005 and 2011, Dr O'Brien was also employed as a researcher at Proteome Sciences Plc in London, developing proteomic strategies for drug target discovery in CNS-related disorders.
Darragh heads the newly established Structural & Mechanistic Proteomics laboratory within the Nuffield Department of Medicine, which uses advanced proteomics and Hydrogen-Deuterium eXchange Mass Spectrometry (HDX-MS) technologies to characterise the structure and conformational dynamics of biological systems.
Dr O'Brien is a Research Fellow of Green Templeton College.
For collaboration enquiries, please contact darragh.obrien@ndm.ox.ac.uk
Recent publications
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Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.
Journal article
O'Brien DP. et al, (2025), J Proteome Res, 24, 479 - 490
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Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.
Journal article
Fowler SL. et al, (2024), Nat Neurosci
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Altered Hormone and Bioactive Lipid Plasma Profile in Rodent Models of Polycystic Ovarian Syndrome Revealed by Targeted Mass Spectrometry
Preprint
Scott HC. et al, (2024)
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Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor
Preprint
O’Brien DP. et al, (2024)
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Deubiquitinases in muscle physiology and disorders.
Journal article
Olie CS. et al, (2024), Biochem Soc Trans, 52, 1085 - 1098