Dynamic gene regulation
Our lab aims to understand how different types of gene expression dynamics are generated and what their consequences are for the organism. Many genes are not simply ‘off’ or ‘on’ but rather their expression varies over time in a complex manner. For example, circadian clock genes show oscillations in their expression level with a period of approximately 24 hours. In bacteria, stress responsive transcriptional regulators show stochastic pulses of activation, with heterogeneity between genetically identical cells. These different types of dynamics are controlled by gene regulatory networks and influenced by stochasticity due to the low numbers of molecules involved. We aim to understand the design principles of gene regulatory networks and how they operate within a stochastic context. We do this by using single-cell time-lapse microscopy to measure gene expression dynamics in individual bacterial and plant cells and using computational modelling to explore hypotheses for how the dynamics are generated. This is important for us to understand how organisms such as bacteria and plants anticipate and respond to environmental changes.
Lab Members
Dr Katie Abley
Project Manager
Dr Rituparna Goswami
Research Associate
Mana Afsharinafar
Research Assistant
Dr James Locke
Research Group Leader
Enrico Sandro Colizzi
Research Associate
Torkel Loman
PhD Student
Sasha Eremina
PhD Student
Chris Micklem
PhD Student
Research Assistant
Dr Christian Schwall
Research Associate
Chao Ye
PhD Student
Lisa Walker
Personal Assistant
Alumni
Mirela Domijan (Research Associate) - Lecturer, University of Liverpool
Douglas Griffith (Research Assistant) - Senior Researcher, LMU Munich
Casandra Villava (Research Assistant) - Research Technician, EMBL Barcelona
Benoit Landrein (Research Associate) - CNRS Independent Researcher
Niall Murphy (Research Associate) - equal1.labs
Om Patange (PhD student) - Postdoc, Harvard Medical School
Bruno Martins (Research Associate) - Assistant Professor, University of Warwick
Sandra Cortijo (Research Associate) - CNRS Independent Researcher
Pau Formosa-Jordan (Herchel Smith Post Doctoral Research Fellow) - Group Leader, Max Planck Institute for Plant Breeding Research
Mark Greenwood (Research Associate) - Postdoc, MIT
Publications
A full publication list can be found on google scholar: https://scholar.google.co.uk/citations?user=U6GUf8YAAAAJ&hl=en
Selected Locke Lab publications
Tunable phenotypic variability through an autoregulatoty alternative sigma factor circuit (2021)
CP Schwall, TE Loman, BMC Martins, S Cortijo, C Villava,
V Kusmartsev, T Livesey, T Saez, JCW Locke
Molecular Systems Biology 17:e9832
K Abley, P Formosa-Jordan, H Tavares, EYT Chan, M Afsharinafar, O Leyser, JCW Locke
eLife 10:e59485
E Nadezhdin, N Murphy, N Dalchau, A Phillips, JCW Locke
Nature communications 11 (1), 1-12
S Cortijo, M Bhattarai, JCW Locke, SE Ahnert
Frontiers in plant science 11
Does gene expression noise play a functional role in plants? (2020)
S Cortijo, JCW Locke
Trends in Plant Science
M Greenwood, JCW Locke
Current opinion in plant biology 53, 65-72
Coordinated circadian timing through the integration of local inputs in Arabidopsis thaliana (2019)
M Greenwood, M Domijan, PD Gould, AJW Hall, JCW Locke
PLoS biology 17 (8), e3000407
Widespread inter‐individual gene expression variability in Arabidopsis thaliana (2019)
S Cortijo, Z Aydin, S Ahnert, JCW Locke
Molecular systems biology 15 (1), e8591
IT Tokuda, OE Akman, JCW Locke
Journal of theoretical biology 463, 155-166
Escherichia coli can survive stress by noisy growth modulation (2018)
Om Patange, Christian Schwall, Matt Jones, Casandra Villava, Douglas A Griffith, Andrew Phillips, James CW Locke
Nature communications 9 (1), 1-11
Cell size control driven by the circadian clock and environment in cyanobacteria (2018)
BMC Martins, AK Tooke, P Thomas, JCW Locke
Proceedings of the National Academy of Sciences 115 (48), E11415-E11424
Peter D Gould, Mirela Domijan, Mark Greenwood, Isao T Tokuda, Hannah Rees, Laszlo Kozma-Bognar, Anthony JW Hall, James CW Locke
Elife 7, e31700
Molecular time sharing through dynamic pulsing in single cells (2018)
Jin Park, Marta Dies, Yihan Lin, Sahand Hormoz, Stephanie E Smith-Unna, Sofia Quinodoz, María Jesús Hernández-Jiménez, Jordi Garcia-Ojalvo, James CW Locke, Michael B Elowitz
Cell systems 6 (2), 216-229. e15
Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins (2018)
Benoit Landrein, Pau Formosa-Jordan, Alice Malivert, Christoph Schuster, Charles W Melnyk, Weibing Yang, Colin Turnbull, Elliot M Meyerowitz, James CW Locke, Henrik Jönsson
Proceedings of the National Academy of Sciences 115 (6), 1382-1387
Heather M Meyer, José Teles, Pau Formosa-Jordan, Yassin Refahi, Rita San-Bento, Gwyneth Ingram, Henrik Jönsson, James CW Locke, Adrienne HK Roeder
Elife 6, e19131
Frequency doubling in the cyanobacterial circadian clock (2016)
BMC Martins, AK Das, L Antunes, JCW Locke
Molecular systems biology 12 (12), 896
Developmental mechanisms underlying variable, invariant and plastic phenotypes (2016)
K Abley, JCW Locke, HMO Leyser
Annals of botany 117 (5), 733-748
Microbial individuality: how single-cell heterogeneity enables population level strategies (2015)
BMC Martins, JCW Locke
Current opinion in microbiology 24, 104-112
ELF3 controls thermoresponsive growth in Arabidopsis (2015)
Mathew S Box, B Emma Huang, Mirela Domijan, Katja E Jaeger, Asif Khan Khattak, Seong Jeon Yoo, Emma L Sedivy, D Marc Jones, Timothy J Hearn, Alex AR Webb, Alastair Grant, James CW Locke, Philip A Wigge
Current biology 25 (2), 194-199
A selection of James Locke's previous publications
Rate of environmental change determines stress response specificity (2013)
JW Young*, JCW Locke*, MB Elowitz
Proceedings of the National Academy of Sciences 110 (10), 4140-4145
Stochastic pulse regulation in bacterial stress response (2011)
JCW Locke, JW Young, M Fontes, MJH Jiménez, MB Elowitz
Science 334 (6054), 366
Using movies to analyse gene circuit dynamics in single cells (2009)
JCW Locke, MB Elowitz
Nature Reviews Microbiology 7 (5), 383-392
James CW Locke, László Kozma‐Bognár, Peter D Gould, Balázs Fehér, Eva Kevei, Ferenc Nagy, Matthew S Turner, Anthony Hall, Andrew J Millar
Molecular systems biology 2 (1), 59
JCW Locke, AJ Millar, MS Turner
Journal of theoretical biology 234 (3), 383-393
Extension of a genetic network model by iterative experimentation and mathematical analysis (2005)
James CW Locke, Megan M Southern, László Kozma‐Bognár, Victoria Hibberd, Paul E Brown, Matthew S Turner, Andrew J Millar
Molecular systems biology 1 (1), 2005.0013