John S. O'Neill

John Stuart O’Neill (born 2 June 1979) is a British molecular and circadian biologist. O’Neill is currently a Principal Investigator at the MRC Laboratory of Molecular Biology in Cambridge, United Kingdom.[1] His work focuses on the fundamental mechanisms that sustain circadian rhythms in eukaryotic cells.

John Stuart O'Neill
Born (1979-06-02) 2 June 1979
Doncaster, United Kingdom
Alma mater
Scientific career
FieldsChronobiology
InstitutionsLaboratory of Molecular Biology
ThesisThe molecular biology of mammalian circadian rhythms (2007)

Academic career

O'Neill studied undergraduate biochemistry at New College, Oxford.[2] He went on to join King's College, Cambridge,[3] where he undertook his PhD research at the MRC Laboratory of Molecular Biology, under the supervision of Michael Hastings, on the subject of cAMP signalling in the suprachiasmatic nucleus of the hypothalamus (SCN).[4]

For his post-doctoral research, O’Neill investigated circadian rhythms in plants and algae with Andrew Millar at the University of Edinburgh and then subsequently in human cells with Akhilesh Reddy at the Institute for Metabolic Science at the University of Cambridge. During this time, O’Neill contributed to a number of papers on non-transcriptional mechanisms of circadian timekeeping,[5][6] most notably a letter and an article in same edition of Nature showing that transcriptional cycles are not essential for circadian rhythms in human and algal cells,[7][8] which have been cited over 700 and 400 times respectively, according to Google Scholar.[9] These observations were subsequently independently replicated [10][11][12] and extended[13][14][15] but were considered controversial at the time since transcriptional feedback repression had been thought essential for circadian rhythms in eukaryotes.[16][17]

O'Neill was awarded a Wellcome Trust Career Development Fellowship in 2011 and in 2013 was recruited to become an independent group leader in the Cell Biology Division of the MRC Laboratory of Molecular Biology. In 2016, he was awarded an EMBO Young Investigator Prize. In collaboration with Cairn Research, O'Neill pioneered the development of the ALLIGATOR for long-term bioluminescence imaging.[18]

Current Research

The O'Neill group’s research is focused on the evolution and mechanisms of circadian timekeeping in eukaryotic cells,[19][20][21] and how biological clocks regulate cellular function to impact upon human health and disease.[22][23] In a 2019 paper, published in the journal Cell, the group identified insulin as a primary signal synchronizing mammalian circadian rhythms with feeding time.[24] In 2017, the lab also demonstrated that cell-autonomous circadian regulation of actin dynamics in fibroblast and other skin cells leads to differences in cell migration during wound healing that depend on the biological time of day that the wound was incurred. These findings predicted the striking 40% difference in the number of days that human burn injuries required to heal which they subsequently identified. Most recently, the O'Neill lab has been working to determine the basis for understanding metabolic oscillations in yeast.[25]

References
  1. https://www2.mrc-lmb.cam.ac.uk/group-leaders/n-to-s/john-oneill/ Laboratory Website
  2. "Dr John O'Neill". St John's College, Cambridge. Retrieved 18 March 2019.
  3. University of Cambridge (25 July 2007). "Acta: Congregation of the Regent House on 21 July 2007". Cambridge University Reporter. 137 (36). Retrieved 18 March 2019.
  4. O'Neill, J. S; Maywood, E. S; Chesham, J. E; Takahashi, J. S; Hastings, M. H (2008). "CAMP-Dependent Signaling as a Core Component of the Mammalian Circadian Pacemaker". Science. 320 (5878): 949–53. doi:10.1126/science.1152506. PMC 2735813. PMID 18487196.
  5. Hastings, Michael H; Maywood, Elizabeth S; O'Neill, John S (2008). "Cellular Circadian Pacemaking and the Role of Cytosolic Rhythms". Current Biology. 18 (17): R805–R815. doi:10.1016/j.cub.2008.07.021. PMID 18786386. S2CID 10321560.
  6. o'Neill, John S; Maywood, Elizabeth S; Hastings, Michael H (2013). "Cellular Mechanisms of Circadian Pacemaking: Beyond Transcriptional Loops". Circadian Clocks. Handbook of Experimental Pharmacology. Vol. 217. pp. 67–103. doi:10.1007/978-3-642-25950-0_4. ISBN 978-3-642-25949-4. PMID 23604476.
  7. O'Neill, John S; Reddy, Akhilesh B (2011). "Circadian clocks in human red blood cells". Nature. 469 (7331): 498–503. doi:10.1038/nature09702. PMC 3040566. PMID 21270888.
  8. O'Neill, John S; Van Ooijen, Gerben; Dixon, Laura E; Troein, Carl; Corellou, Florence; Bouget, François-Yves; Reddy, Akhilesh B; Millar, Andrew J (2011). "Circadian rhythms persist without transcription in a eukaryote". Nature. 469 (7331): 554–8. doi:10.1038/nature09654. PMC 3040569. PMID 21270895.
  9. "Google Scholar". scholar.google.com. Retrieved 25 April 2018.
  10. Cho, C.-S; Yoon, H. J; Kim, J. Y; Woo, H. A; Rhee, S. G (2014). "Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells". Proceedings of the National Academy of Sciences. 111 (33): 12043–8. doi:10.1073/pnas.1401100111. PMC 4142998. PMID 25092340.
  11. Bouget, François-Yves; Lefranc, Marc; Thommen, Quentin; Pfeuty, Benjamin; Lozano, Jean-Claude; Schatt, Philippe; Botebol, Hugo; Vergé, Valérie (2014). "Transcriptional versus non-transcriptional clocks: A case study in Ostreococcus". Marine Genomics. 14: 17–22. doi:10.1016/j.margen.2014.01.004. PMID 24512973.
  12. Homma, Takujiro; Okano, Satoshi; Lee, Jaeyong; Ito, Junitsu; Otsuki, Noriyuki; Kurahashi, Toshihiro; Kang, Eun Sil; Nakajima, Osamu; Fujii, Junichi (2015). "SOD1 deficiency induces the systemic hyperoxidation of peroxiredoxin in the mouse". Biochemical and Biophysical Research Communications. 463 (4): 1040–6. doi:10.1016/j.bbrc.2015.06.055. PMID 26079888.
  13. Van Ooijen, Gerben; Dixon, Laura E; Troein, Carl; Millar, Andrew J (2011). "Proteasome Function is Required for Biological Timing throughout the Twenty-Four Hour Cycle". Current Biology. 21 (10): 869–75. doi:10.1016/j.cub.2011.03.060. PMC 3102177. PMID 21530263.
  14. Henslee, Erin A; Crosby, Priya; Kitcatt, Stephen J; Parry, Jack S. W; Bernardini, Andrea; Abdallat, Rula G; Braun, Gabriella; Fatoyinbo, Henry O; Harrison, Esther J; Edgar, Rachel S; Hoettges, Kai F; Reddy, Akhilesh B; Jabr, Rita I; von Schantz, Malcolm; O'Neill, John S; Labeed, Fatima H (2017). "Rhythmic potassium transport regulates the circadian clock in human red blood cells". Nature Communications. 8 (1): 1978. doi:10.1038/s41467-017-02161-4. PMC 5719349. PMID 29215003.
  15. Larrondo, L. F; Olivares-Yanez, C; Baker, C. L; Loros, J. J; Dunlap, J. C (2015). "Decoupling circadian clock protein turnover from circadian period determination". Science. 347 (6221): 1257277. doi:10.1126/science.1257277. PMC 4432837. PMID 25635104.
  16. Rosbash, Michael (2009). "The Implications of Multiple Circadian Clock Origins". PLOS Biology. 7 (3): e62. doi:10.1371/journal.pbio.1000062. PMC 2656552. PMID 19296723.
  17. Dunlap, Jay C (1999). "Molecular Bases for Circadian Clocks". Cell. 96 (2): 271–90. doi:10.1016/S0092-8674(00)80566-8. PMID 9988221. S2CID 14991100.
  18. Crosby, Priya; Hoyle, Nathaniel P; O'Neill, John S (2017). "Flexible Measurement of Bioluminescent Reporters Using an Automated Longitudinal Luciferase Imaging Gas- and Temperature-optimized Recorder (ALLIGATOR)". Journal of Visualized Experiments (130). doi:10.3791/56623. PMC 5755584. PMID 29286421.
  19. Causton, Helen C; Feeney, Kevin A; Ziegler, Christine A; O'Neill, John S (2015). "Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms". Current Biology. 25 (8): 1056–62. doi:10.1016/j.cub.2015.02.035. PMC 4406945. PMID 25866393.
  20. Feeney, Kevin A; Hansen, Louise L; Putker, Marrit; Olivares-Yañez, Consuelo; Day, Jason; Eades, Lorna J; Larrondo, Luis F; Hoyle, Nathaniel P; O'Neill, John S; Van Ooijen, Gerben (2016). "Daily magnesium fluxes regulate cellular timekeeping and energy balance". Nature. 532 (7599): 375–9. doi:10.1038/nature17407. PMC 4886825. PMID 27074515.
  21. Putker, Marrit; Crosby, Priya; Feeney, Kevin A; Hoyle, Nathaniel P; Costa, Ana S.H; Gaude, Edoardo; Frezza, Christian; O'Neill, John S (2018). "Mammalian Circadian Period, but Not Phase and Amplitude, is Robust Against Redox and Metabolic Perturbations". Antioxidants & Redox Signaling. 28 (7): 507–520. doi:10.1089/ars.2016.6911. PMC 5806070. PMID 28506121.
  22. Burke, Tina M; Markwald, Rachel R; McHill, Andrew W; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; O'Neill, John S; Wright, Kenneth P (2015). "Effects of caffeine on the human circadian clock in vivo and in vitro". Science Translational Medicine. 7 (305): 305ra146. doi:10.1126/scitranslmed.aac5125. PMC 4657156. PMID 26378246.
  23. Hoyle, Nathaniel P; Seinkmane, Estere; Putker, Marrit; Feeney, Kevin A; Krogager, Toke P; Chesham, Johanna E; Bray, Liam K; Thomas, Justyn M; Dunn, Ken; Blaikley, John; O'Neill, John S (2017). "Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing". Science Translational Medicine. 9 (415): eaal2774. doi:10.1126/scitranslmed.aal2774. PMC 5837001. PMID 29118260.
  24. Crosby, Priya; Hamnett, Ryan; Putker, Marrit; Hoyle, Nathaniel P.; Reed, Martin; Karam, Carolyn J.; Maywood, Elizabeth S.; Stangherlin, Alessandra; Chesham, Johanna E. (April 2019). "Insulin/IGF-1 Drives PERIOD Synthesis to Entrain Circadian Rhythms with Feeding Time". Cell. 177 (4): 896–909.e20. doi:10.1016/j.cell.2019.02.017. PMC 6506277. PMID 31030999.
  25. O’ Neill, John S.; Hoyle, Nathaniel P.; Robertson, J. Brian; Edgar, Rachel S.; Beale, Andrew D.; Peak-Chew, Sew Y.; Day, Jason; Costa, Ana S. H.; Frezza, Christian; Causton, Helen C. (17 September 2020). "Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis". Nature Communications. 11 (1): 4706. doi:10.1038/s41467-020-18330-x. ISSN 2041-1723. PMC 7499178. PMID 32943618.
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