Research Group Leader
James Locke is accepting applications for PhD students.
University of Cambridge
Cambridge CB2 1LR
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. He discovered a novel mode of prokaryotic signal encoding, frequency modulated pulsing.
My main research interest is to gain a quantitative understanding of how cells respond to environmental signals. To do this, I have found that it is critical to observe cellular behaviour at the single cell level as traditional approaches that take an average from a population can obscure heterogeneous responses and novel dynamics. For example, by examining B. subtilis gene expression at the single cell level, I have discovered that the alternative sigma factor sigB is activated in discrete stochastic pulses, a behaviour missed by previous bulk studies (see figure).
My lab will focus on developing a quantitative understanding of signal integration and gene circuit dynamics at the single cell level in Cyanobacteria. Cyanobacteria, which rely on photosynthesis for metabolism, must anticipate day/night cycles, as well as respond to much faster environmental changes. By analyzing gene circuit dynamics at the single cell level in Cyanobacteria, I will develop fundamental insights into how cells respond to diverse, dynamically varying inputs over multiple timescales.
Selected Recent Publications
J Young*, JCW Locke*, MB Elowitz, Rate of environmental change determines stress response specificity, PNAS, 2013, In Press, *joint first authors.
JCW Locke*, J Young*, M Fontes, MB Elowitz, Stochastic pulse regulation in bacterial stress response, Science, 2011 Oct 21;334(6054):366-9, *joint first authors.
C Troein*, JCW Locke*, MS Turner, AJ Millar, Weather and seasons together demand complex biological clocks, Current Biology 2009 19(22):1961-4.*joint first authors.
Selected Recent Reviews
JCW Locke, MB Elowitz , Using movies to analyse gene circuit dynamics in single cells, Nature Reviews Microbiology 2009 7(5):383-92