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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.

Research

What types of dynamic gene regulation do cells use?

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How are dynamic gene circuits coupled together?

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What are possible functions of dynamic gene regulation?

 
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Lab Members

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Dr Katie Abley

Project Manager

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Research Associate

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Mana Afsharinafar

Research Assistant

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Dr James Locke

Research Group Leader

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Sasha Eremina

PhD Student

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Torkel Loman

PhD Student

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Dr Rituparna Goswami

Research Associate

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Chris Micklem

PhD Student

Research Assistant

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Dr Christian Schwall

Research Associate

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Chao Ye

PhD Student

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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

 

Open Positions

We are an interdisciplinary group of biologists, physicists, computer scientists, and mathematicians, working together to try understand the design principles of dynamic gene regulation. If you are interested in joining us, please email James with a cover letter and CV.

 

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

 
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Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms (2020)

E Nadezhdin, N Murphy, N Dalchau, A Phillips, JCW Locke

Nature communications 11 (1), 1-12

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Does gene expression noise play a functional role in plants? (2020)

S Cortijo, JCW Locke

Trends in Plant Science

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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

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Widespread inter‐individual gene expression variability in Arabidopsis thaliana (2019)

S Cortijo, Z Aydin, S Ahnert, JCW Locke

Molecular systems biology 15 (1), e8591

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Reducing the complexity of mathematical models for the plant circadian clock by distributed delays (2019)

IT Tokuda, OE Akman, JCW Locke

Journal of theoretical biology 463, 155-166

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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

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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

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Coordination of robust single cell rhythms in the Arabidopsis circadian clock via spatial waves of gene expression (2018)

Peter D Gould, Mirela Domijan, Mark Greenwood, Isao T Tokuda, Hannah Rees, Laszlo Kozma-Bognar, Anthony JW Hall, James CW Locke

Elife 7, e31700

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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

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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

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Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal (2017)

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

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Frequency doubling in the cyanobacterial circadian clock (2016)

BMC Martins, AK Das, L Antunes, JCW Locke

Molecular systems biology 12 (12), 896

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Developmental mechanisms underlying variable, invariant and plastic phenotypes (2016)

K Abley, JCW Locke, HMO Leyser

Annals of botany 117 (5), 733-748

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Microbial individuality: how single-cell heterogeneity enables population level strategies (2015)

BMC Martins, JCW Locke

Current opinion in microbiology 24, 104-112

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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

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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

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Stochastic pulse regulation in bacterial stress response (2011)

JCW Locke, JW Young, M Fontes, MJH Jiménez, MB Elowitz

Science 334 (6054), 366

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Using movies to analyse gene circuit dynamics in single cells (2009)

JCW Locke, MB Elowitz

Nature Reviews Microbiology 7 (5), 383-392

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Experimental validation of a predicted feedback loop in the multi‐oscillator clock of Arabidopsis thaliana (2006)

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

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Modelling genetic networks with noisy and varied experimental data: the circadian clock in Arabidopsis thaliana (2005)

JCW Locke, AJ Millar, MS Turner

Journal of theoretical biology 234 (3), 383-393

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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

 

Data and Resources

Project code and data for Nadezhdin & Murphy et al 2020, "Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms".

AraNoisy graphical web interface and project code for Cortijo et al., Molecular Systems Biology 2019 "Widespread inter‐individual gene expression variability in Arabidopsis thaliana"

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Project code for Gould et al., 2018, "Coordination of robust single cell rhythms in the Arabidopsis circadian clock".

Research data supporting Martins et al., PNAS 2018, "Cell size control driven by the circadian clock and environment in cyanobacteria".

Research data supporting Landrein et al., PNAS 2018 "Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins"

Contact Us

The Sainsbury Laboratory
University of Cambridge
Cambridge
UK