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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

 

Research supported by grants from

  

Research Group Leader
Royal Society University Research Fellow
Dr James  Locke

Contact Details

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