Journal article
Personalized phosphoproteomics identifies functional signaling
EJ Needham, JR Hingst, BL Parker, KR Morrison, G Yang, J Onslev, JM Kristensen, K Højlund, NXY Ling, JS Oakhill, EA Richter, B Kiens, J Petersen, C Pehmøller, DE James, JFP Wojtaszewski, SJ Humphrey
Nature Biotechnology | Published : 2022
Abstract
Protein phosphorylation dynamically integrates environmental and cellular information to control biological processes. Identifying functional phosphorylation amongst the thousands of phosphosites regulated by a perturbation at a global scale is a major challenge. Here we introduce ‘personalized phosphoproteomics’, a combination of experimental and computational analyses to link signaling with biological function by utilizing human phenotypic variance. We measure individual subject phosphoproteome responses to interventions with corresponding phenotypes measured in parallel. Applying this approach to investigate how exercise potentiates insulin signaling in human skeletal muscle, we identify ..
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Awarded by University of Sydney
Funding Acknowledgements
We thank S. Kurdyukov, A. Zadoorian, I. Beck Nielsen, B. Bolmgren and L. Hansen for technical assistance. We thank E. Pickering and members of the Metabolic Systems Biology group, Pfizer Cardiovascular and Metabolic Diseases Research Unit and the Molecular Physiology section of the University of Copenhagen for feedback and discussions. AMPK alpha double-knockout MEFs were kindly provided by B. Viollet. This research was facilitated by access to Sydney Mass Spectrometry, a core research facility at the University of Sydney. This work was funded by: Pfizer, Inc.; Australian Government Research Training Program Scholarship and the University of Sydney Val Street Scholarship (to E.J.N.); ARC Laureate Fellowship (no. FL200100096 to D.E.J.); NHMRC Project Grant (no. APP1122376 to B.L.P.); APP1161262 (to J.S.O.); ARC Discovery Project Grant (no. DP180101682 to J.P.); Danish Council for In-dependent Research Medical Sciences (no. FSS 8020-00288 to J.F.P.W.); Ministry of Culture Denmark (no. FPK 2016-0027 to J.F.P.W.); The Novo Nordisk Foundation (no. NNF16OC 0023046 to J.F.P.W.); The University of Sydney University of Copenhagen Partnership Collaboration Awards (to J.F.P.W. and D.E.J.); the Victorian Government's Operational Infrastructure Support Program (to J.S.O.); a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant number NNF17SA0031406 (J.O.).