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Sainsbury Laboratory

James graduated from the University of Warwick (2000) in Physics, before completing Maths Part III at Cambridge (2001). James then studied for a joint PhD in Biology and Theoretical Physics at the University of Warwick, with supervision from Professors Andrew Millar and Matthew Turner. During his PhD James used an iterative process of experiment and theory to propose a new feedback loop in the plant circadian (24-hour) clock. For this work he was awarded the Promega Young Geneticist of the Year award (2007). As first an EMBO Research Fellow and then a Human Frontiers Fellow, James conducted his postdoctoral work in the lab of Professor Michael Elowitz at the California Institute of Technology. He applied single cell time-lapse microscopy, modelling, and synthetic biology techniques to understand how cells amplify small molecule differences (noise) into alternative transcriptional states. . Since 2012 he has been a group leader at the Sainsbury laboratory investigating gene expression dynamics in microbial and plant systems. He was awarded the Merrimack-CSB2 Prize in Systems Biology in 2013 and a Royal Society University Fellowship in 2015.

Downstream targets of the cyanobacterial circadian clock can double their frequency from one peak to two peaks every 24 hours through an oscillatory incoherent feedforward loop circuit.

Sub-tissue level resolution LUC imaging of a clock reporter revealed mechanism for clock coordination in seedlings through local cell-cell coupling that generates spatial waves.

 

Selected Recent Publications

CP Schwall, TE Loman, BMC Martins, S Cortijo, C Villava, V Kusmartsev, T Livesey, T Saez, JCW LockeTunable phenotypic variability through an autoregulatory alternative sigma factor circuit, Molecular Systems Biology, 2021; 17:e9832

K Abley, P Formosa-Jordan, H Tavares, EYT Chan, M Afsharinafar, O Leyser^, JCW Locke^An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time , eLife, 2021; 10:e59485

E Nadezhdin, N Murphy, N Dalchau, A Phillips, JCW LockeStochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms, Nature communications, 2020; 11 (1), 1-12

S Cortijo, M Bhattarai, JCW Locke^, SE Ahnert^, Co-expression networks from gene expression variability between genetically identical seedlings can reveal novel regulatory relationships, Frontiers in plant science, 2020; 11:599464

M Greenwood, M Domijan, PD Gould, AJW Hall, JCW LockeCoordinated circadian timing through the integration of local inputs in Arabidopsis thaliana, PLoS biology, 2019; 17 (8), e3000407

S Cortijo, Z Aydin, S Ahnert, JCW LockeWidespread inter-individual gene expression variability in Arabidopsis thaliana , Molecular systems biology, 2019; 15 (1), e8591

O Patange, C Schwall, M Jones, C Villava, DA Griffith, A Phillips, JCW LockeEscherichia coli can survive stress by noisy growth modulation, Nature communications, 2018; 9 (1), 1-11

BMC Martins, AK Tooke, P Thomas, JCW Locke, Cell size control driven by the circadian clock and environment in cyanobacteria, PNAS, 2018; (48), E11415-E11424

P Gould*, M Domijan*, M Greenwood, IT Tokuda, H Rees, L Kozma-Bognar, AJW Hall^, JCW Locke^Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression, eLife, 2018; 7, e31700

J Park, M Dies, Y Lin, S Hormoz, SE Smith-Unna, S Quinodoz, M Hernández-Jiménez, J Garcia-Ojalvo^, JCW Locke^, MB Elowitz^, Molecular time-sharing through dynamic pulsing in single cells, Cell Systems, 2018; 6 (2), 216-229.

B Landrein, P Jordan-Formosa, C Melnyk, C Schuster, W Yang, C Turnbull, EM Meyerowitz^, JCW Locke^, H Jönsson^, Nitrate modulates stem cell dynamics by regulating WUSCHEL expression through cytokinins, PNAS, 2018; Feb 6;115(6):1382-1387.

HM Meyer*, J Teles*, P Formosa-Jordan*, Y Refahi, R San-Bento, G Ingram, H Jönsson^, JCW Locke^, AHK Roeder^, Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal, eLife, 2017; e19131.

BMC Martins*, AK Das*, L Antunes, JCW Locke, Frequency doubling in the cyanobacterial circadian clock, Molecular Systems Biology, 2016; 12 (12), 896. https://www.embopress.org/doi/full/10.15252/msb.20209832

 

Selected Recent Reviews

CN Micklem, JCW LockeCut the noise or couple up: Coordinating circadian and synthetic clocksiScience, 2021;  24 (9), 103051

S Cortijo, JCW LockeDoes gene expression noise play a functional role in plants? Trends in Plant Science, 2020; 25 (10), 1041-1051

M Greenwood, JCW LockeThe circadian clock coordinates plant development through specificity at the tissue and cellular level, Current opinion in plant biology, 2020; 53, 65-72

K Abley, JCW Locke, HMO Leyser, Developmental mechanisms underlying variable, invariant and plastic phenotypes, Annals of Botany, 2016; 117 (5), 733-748.

BMC Martins, JCW Locke, Microbial individuality: how single-cell heterogeneity enables population level strategies, Current Opinion in Microbiology, 2015; 24, 104-112.

*Joint first authors

 ^Joint corresponding authors

Selected Recent Reviews

CN Micklem, JCW LockeCut the noise or couple up: Coordinating circadian and synthetic clocksiScience, 2021;  24 (9), 103051

S Cortijo, JCW LockeDoes gene expression noise play a functional role in plants? Trends in Plant Science, 2020; 25 (10), 1041-1051

M Greenwood, JCW LockeThe circadian clock coordinates plant development through specificity at the tissue and cellular level, Current opinion in plant biology, 2020; 53, 65-72

K Abley, JCW Locke, HMO Leyser, Developmental mechanisms underlying variable, invariant and plastic phenotypes, Annals of Botany, 2016; 117 (5), 733-748.

BMC Martins, JCW Locke, Microbial individuality: how single-cell heterogeneity enables population level strategies, Current Opinion in Microbiology, 2015; 24, 104-112.

*Joint first authors

 ^Joint corresponding authors

 

Research supported by grants from

European Union, European Research Council and Gatsby Charitable Foundation.

  

Publications from Elements

Journal articles

2024

  • Abley, K., Goswami, R. and Locke, JCW., 2024. Bet-hedging and variability in plant development: seed germination and beyond. Philos Trans R Soc Lond B Biol Sci, v. 379
    Doi: http://doi.org/10.1098/rstb.2023.0048
  • 2023

  • Loman, TE. and Locke, JCW., 2023. The σB alternative sigma factor circuit modulates noise to generate different types of pulsing dynamics. PLoS Comput Biol, v. 19
    Doi: http://doi.org/10.1371/journal.pcbi.1011265
  • 2022

  • Greenwood, M., Tokuda, IT. and Locke, JCW., 2022. A spatial model of the plant circadian clock reveals design principles for coordinated timing. Mol Syst Biol, v. 18
    Doi: http://doi.org/10.15252/msb.202010140
  • Davis, W., Endo, M. and Locke, JCW., 2022. Spatially specific mechanisms and functions of the plant circadian clock. Plant Physiol, v. 190
    Doi: http://doi.org/10.1093/plphys/kiac236
  • 2021

  • Abley, K., Formosa-Jordan, P., Tavares, H., Chan, EY., Afsharinafar, M., Leyser, O. and Locke, JC., 2021. An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time. Elife, v. 10
    Doi: 10.7554/eLife.59485
  • Schwall, CP., Loman, TE., Martins, BMC., Cortijo, S., Villava, C., Kusmartsev, V., Livesey, T., Saez, T. and Locke, JCW., 2021. Tunable phenotypic variability through an autoregulatory alternative sigma factor circuit. Mol Syst Biol, v. 17
    Doi: http://doi.org/10.15252/msb.20209832
  • Abley, K. and Locke, JCW., 2021. Noisy transcription under the spotlight. Nat Plants, v. 7
    Doi: http://doi.org/10.1038/s41477-021-00987-x
  • Micklem, CN. and Locke, JCW., 2021. Cut the noise or couple up: Coordinating circadian and synthetic clocks. iScience, v. 24
    Doi: http://doi.org/10.1016/j.isci.2021.103051
  • 2020

  • Greenwood, M. and Locke, JC., 2020. The circadian clock coordinates plant development through specificity at the tissue and cellular level. Curr Opin Plant Biol, v. 53
    Doi: http://doi.org/10.1016/j.pbi.2019.09.004
  • Nadezhdin, E., Murphy, N., Dalchau, N., Phillips, A. and Locke, JCW., 2020. Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms. Nat Commun, v. 11
    Doi: http://doi.org/10.1038/s41467-020-14431-9
  • Cortijo, S. and Locke, JCW., 2020. Does Gene Expression Noise Play a Functional Role in Plants? Trends Plant Sci, v. 25
    Doi: http://doi.org/10.1016/j.tplants.2020.04.017
  • Abley, K., Formosa-Jordan, P., Tavares, H., Chan, E., Leyser, O. and Locke, JCW., 2020. An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time
    Doi: 10.1101/2020.06.05.135681
  • Grant, PK., Szep, G., Patange, O., Halatek, J., Coppard, V., Csikász-Nagy, A., Haseloff, J., Locke, JCW., Dalchau, N. and Phillips, A., 2020. Interpretation of morphogen gradients by a synthetic bistable circuit. Nat Commun, v. 11
    Doi: http://doi.org/10.1038/s41467-020-19098-w
  • Cortijo, S., Bhattarai, M., Locke, JCW. and Ahnert, SE., 2020. Co-expression Networks From Gene Expression Variability Between Genetically Identical Seedlings Can Reveal Novel Regulatory Relationships. Front Plant Sci, v. 11
    Doi: http://doi.org/10.3389/fpls.2020.599464
  • 2019

  • Tokuda, IT., Akman, OE. and Locke, JCW., 2019. Reducing the complexity of mathematical models for the plant circadian clock by distributed delays. J Theor Biol, v. 463
    Doi: http://doi.org/10.1016/j.jtbi.2018.12.014
  • Cortijo, S., Aydin, Z., Ahnert, S. and Locke, JC., 2019. Widespread inter-individual gene expression variability in Arabidopsis thaliana. Mol Syst Biol, v. 15
    Doi: http://doi.org/10.15252/msb.20188591
  • Greenwood, M., Domijan, M., Gould, PD., Hall, AJW. and Locke, JCW., 2019. Coordinated circadian timing through the integration of local inputs in Arabidopsis thaliana. PLoS Biol, v. 17
    Doi: http://doi.org/10.1371/journal.pbio.3000407
  • 2018 (Accepted for publication)

  • Locke, JCW., 2018 (Accepted for publication). Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression eLife,
  • 2018

  • Jonsson, H., Meyerowitz, , Landrein, BPM., Formosa-Jordan, , Malivert, , Schuster, C., Melnyk, CW., Yang, W., Turnbull, and Locke, JCW., 2018. Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins Proceedings of the National Academy of Sciences of the United States of America, v. 115
    Doi: 10.1073/pnas.1718670115
  • Locke, JCW., 2018. Molecular ​​time-sharing ​​through​​ dynamic ​​pulsing ​​in ​​single ​​cells Cell Systems, v. 6
    Doi: http://doi.org/10.1016/j.cels.2018.01.011
  • Martins, B. and Locke, J., 2018. Every microbe matters: Making movies of single cells Microbiology Today, v. 45
  • Mosheiff, N., Martins, BMC., Pearl-Mizrahi, S., Grünberger, A., Helfrich, S., Mihalcescu, I., Kohlheyer, D., Locke, JCW., Glass, L. and Balaban, NQ., 2018. Inheritance of Cell-Cycle Duration in the Presence of Periodic Forcing Physical Review X, v. 8
    Doi: http://doi.org/10.1103/PhysRevX.8.021035
  • Locke, JCW., Thomas, P., Martins, B. and Tooke, A., 2018. Cell size control driven by the circadian clock and environment in cyanobacteria Proceedings of the National Academy of Sciences of the United States of America,
  • Patange, O., Schwall, C., Jones, M., Villava, C., Griffith, DA., Phillips, A. and Locke, JCW., 2018. Escherichia coli can survive stress by noisy growth modulation. Nat Commun, v. 9
    Doi: http://doi.org/10.1038/s41467-018-07702-z
  • 2017 (Accepted for publication)

  • Meyer, HM., Teles, J., Formosa-Jordan, P., Refahi, Y., San-Bento, R., Ingram, G., Jönsson, H., Locke, JCW. and Roeder, AHK., 2017 (Accepted for publication). Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the $\textit{Arabidopsis}$ sepal eLife, v. 6
    Doi: 10.7554/eLife.19131
  • 2017

  • Landrein, B., Formosa-Jordan, P., Malivert, A., Schuster, C., Melnyk, C., Yang, W., Turnbull, C., Meyerowitz, E., Locke, JCW. and Jönsson, H., 2017. Nitrate modulates stem cell dynamics by regulating<i>WUSCHEL</i>expression through cytokinins
    Doi: 10.1101/200303
  • 2016

  • Abley, K., Locke, JCW. and Leyser, HMO., 2016. Developmental mechanisms underlying variable, invariant and plastic phenotypes. Ann Bot, v. 117
    Doi: 10.1093/aob/mcw016
  • Jung, J-H., Domijan, M., Klose, C., Biswas, S., Ezer, D., Gao, M., Khattak, AK., Box, MS., Charoensawan, V., Cortijo, S., Kumar, M., Grant, A., Locke, JCW., Schäfer, E., Jaeger, KE. and Wigge, PA., 2016. Phytochromes function as thermosensors in $\textit{Arabidopsis}$ Science, v. 354
    Doi: http://doi.org/10.1126/science.aaf6005
  • Martins, BM., Das, AK., Antunes, L. and Locke, JC., 2016. Frequency doubling in the cyanobacterial circadian clock Molecular Systems Biology, v. 12
    Doi: http://doi.org/10.15252/msb.20167087
  • 2015

  • Box, MS., Huang, BE., Domijan, M., Jaeger, KE., Khattak, AK., Yoo, SJ., Sedivy, EL., Jones, DM., Hearn, TJ., Webb, AAR., Grant, A., Locke, JCW. and Wigge, PA., 2015. ELF3 controls thermoresponsive growth in Arabidopsis. Curr Biol, v. 25
    Doi: http://doi.org/10.1016/j.cub.2014.10.076
  • Martins, BMC. and Locke, JCW., 2015. Microbial individuality: how single-cell heterogeneity enables population level strategies. Curr Opin Microbiol, v. 24
    Doi: http://doi.org/10.1016/j.mib.2015.01.003
  • Patron, NJ., Orzaez, D., Marillonnet, S., Warzecha, H., Matthewman, C., Youles, M., Raitskin, O., Leveau, A., Farré, G., Rogers, C., Smith, A., Hibberd, J., Webb, AAR., Locke, J., Schornack, S., Ajioka, J., Baulcombe, DC., Zipfel, C., Kamoun, S., Jones, JDG., Kuhn, H., Robatzek, S., Van Esse, HP., Sanders, D., Oldroyd, G., Martin, C., Field, R., O'Connor, S., Fox, S., Wulff, B., Miller, B., Breakspear, A., Radhakrishnan, G., Delaux, P-M., Loqué, D., Granell, A., Tissier, A., Shih, P., Brutnell, TP., Quick, WP., Rischer, H., Fraser, PD., Aharoni, A., Raines, C., South, PF., Ané, J-M., Hamberger, BR., Langdale, J., Stougaard, J., Bouwmeester, H., Udvardi, M., Murray, JAH., Ntoukakis, V., Schäfer, P., Denby, K., Edwards, KJ., Osbourn, A. and Haseloff, J., 2015. Standards for plant synthetic biology: a common syntax for exchange of DNA parts. New Phytologist, v. 208
    Doi: http://doi.org/10.1111/nph.13532
  • 2013

  • Locke, JCW., 2013. Systems biology: How bacteria choose a lifestyle Nature, v. 503
    Doi: http://doi.org/10.1038/nature12837
  • Young, JW., Locke, JCW. and Elowitz, MB., 2013. Rate of environmental change determines stress response specificity PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 110
    Doi: http://doi.org/10.1073/pnas.1213060110
  • 2012

  • Young, JW., Locke, JCW., Altinok, A., Rosenfeld, N., Bacarian, T., Swain, PS., Mjolsness, E. and Elowitz, MB., 2012. Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy NAT PROTOC, v. 7
    Doi: http://doi.org/10.1038/nprot.2011.432
  • 2011

  • John, M., 2011. A is for Abstract. HSR Proc Intensive Care Cardiovasc Anesth, v. 3
  • Locke, JCW., Young, JW., Fontes, M., Jiménez, MJH. and Elowitz, MB., 2011. Stochastic pulse regulation in bacterial stress response Science, v. 334
    Doi: http://doi.org/10.1126/science.1208144
  • Wenden, B., Kozma-Bognár, L., Edwards, KD., Hall, AJW., Locke, JCW. and Millar, AJ., 2011. Light inputs shape the Arabidopsis circadian system Plant Journal, v. 66
    Doi: http://doi.org/10.1111/j.1365-313X.2011.04505.x
  • 2009

  • Salazar, JD., Saithong, T., Brown, PE., Foreman, J., Locke, JCW., Halliday, KJ., Carré, IA., Rand, DA. and Millar, AJ., 2009. Prediction of Photoperiodic Regulators from Quantitative Gene Circuit Models Cell, v. 139
    Doi: http://doi.org/10.1016/j.cell.2009.11.029
  • Troein, C., Locke, JCW., Turner, MS. and Millar, AJ., 2009. Weather and Seasons Together Demand Complex Biological Clocks Current Biology, v. 19
    Doi: http://doi.org/10.1016/j.cub.2009.09.024
  • Locke, JCW. and Elowitz, MB., 2009. Using movies to analyse gene circuit dynamics in single cells Nature Reviews Microbiology, v. 7
    Doi: http://doi.org/10.1038/nrmicro2056
  • 2008

  • Locke, JCW., Westermark, PO., Kramer, A. and Herzel, H., 2008. Global parameter search reveals design principles of the mammalian circadian clock BMC Systems Biology, v. 2
    Doi: http://doi.org/10.1186/1752-0509-2-16
  • Akman, OE., Locke, JCW., Tang, S., Carré, I., Millar, AJ. and Rand, DA., 2008. Isoform switching facilitates period control in the Neurospora crassa circadian clock Molecular Systems Biology, v. 4
    Doi: http://doi.org/10.1038/msb.2008.5
  • 2006

  • Slack, JL., Locke, JCW., Song, S-W., Ona, J. and Richardson, TJ., 2006. Metal hydride switchable mirrors: Factors influencing dynamic range and stability Solar Energy Materials and Solar Cells, v. 90
    Doi: http://doi.org/10.1016/j.solmat.2005.02.015
  • Edwards, KD., Anderson, PE., Hall, A., Salathia, NS., Locke, JCW., Lynn, JR., Straume, M., Smith, JQ. and Millar, AJ., 2006. FLOWERING LOCUS C mediates natural variation in the high-temperature response of the Arabidopsis circadian clock Plant Cell, v. 18
    Doi: http://doi.org/10.1105/tpc.105.038315
  • 2005

  • Locke, JCW., Millar, AJ. and Turner, MS., 2005. Modelling genetic networks with noisy and varied experimental data: The circadian clock in Arabidopsis thaliana Journal of Theoretical Biology, v. 234
    Doi: http://doi.org/10.1016/j.jtbi.2004.11.038
  • Le Quéré, P., Weisman, C., Paillère, H., Vierendeels, J., Dick, E., Becker, R., Braack, M. and Locke, J., 2005. Modelling of Natural Convection Flows with Large Temperature Differences: A Benchmark Problem for Low Mach Number Solvers. Part 1. Reference Solutions ESAIM: Mathematical Modelling and Numerical Analysis, v. 39
    Doi: http://doi.org/10.1051/m2an:2005027
  • Locke, JCW., Southern, MM., Kozma-Bognár, L., Hibberd, V., Brown, PE., Turner, MS. and Millar, AJ., 2005. Extension of a genetic network model by iterative experimentation and mathematical analysis. Molecular systems biology, v. 1
    Doi: http://doi.org/10.1038/msb4100018
  • Book chapters

    2022

  • Greenwood, M., Hall, AJW. and Locke, JCW., 2022. High Spatial Resolution Luciferase Imaging of the Arabidopsis thaliana Circadian Clock.
    Doi: http://doi.org/10.1007/978-1-0716-1912-4_4
  • Datasets

    2021 (No publication date)

  • Abley, K., Tavares, H., Formosa-Jordan, P., Chan, EYT., Afsharinafar, M., Leyser, O. and Locke, J., 2021 (No publication date). Data supporting 'An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time', Abley & Formosa-Jordan et al., eLife (2021)
  • 2018 (No publication date)

  • Landrein, BPM., Formosa-Jordan, P., Malivert, A., Schuster, C., Melnyk, CW., Yang, W., Turnbull, C., Meyerowitz, EM., Locke, JCW. and Jönsson, H., 2018 (No publication date). Research data supporting "Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins"
  • Locke, JCW., Gould, P., Hall, A. and Domijan, M., 2018 (No publication date). Research Data supporting Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression
  • Locke, JCW., Martins, B., Thomas, P. and Tooke, A., 2018 (No publication date). Research data supporting Cell size control driven by the circadian clock and environment in cyanobacteria
  • Internet publications

    2018

  • Cortijo, S., Aydin, Z., Ahnert, S. and Locke, J., 2018. Widespread inter-individual gene expression variability in<i>Arabidopsis thaliana</i>
    Doi: http://doi.org/10.1101/335380
  • Conference proceedings

    2017

  • Patange, O., Schwall, C., Griffith, D., Phillips, A. and Locke, J., 2017. Functional phenotypic variability via growth rate mediated feedback in Escherichia coli EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, v. 46
  • Professor of Quantitative Plant Development
    Associate Director
    Research Group Leader
    Dr James  Locke

    Contact Details

    Sainsbury Laboratory
    University of Cambridge
    47 Bateman Street
    Cambridge
    CB2 1LR