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Murray P.J.,Mathematical Institute | Maini P.K.,Mathematical Institute | Maini P.K.,Oxford Center for Integrative Systems Biology | Baker R.E.,Mathematical Institute
Developmental Biology | Year: 2013

The discovery over the last 15 years of molecular clocks and gradients in the pre-somitic mesoderm of numerous vertebrate species has added significant weight to Cooke and Zeeman's 'clock and wavefront' model of somitogenesis, in which a travelling wavefront determines the spatial position of somite formation and the somitogenesis clock controls periodicity (Cooke and Zeeman, 1976). However, recent high-throughput measurements of spatiotemporal patterns of gene expression in different zebrafish mutant backgrounds allow further quantitative evaluation of the clock and wavefront hypothesis. In this study we describe how our recently proposed model, in which oscillator coupling drives the propagation of an emergent wavefront, can be used to provide mechanistic and testable explanations for the following observed phenomena in zebrafish embryos: (a) the variation in somite measurements across a number of zebrafish mutants; (b) the delayed formation of somites and the formation of 'salt and pepper' patterns of gene expression upon disruption of oscillator coupling; and (c) spatial correlations in the 'salt and pepper' patterns in Delta-Notch mutants. In light of our results, we propose a number of plausible experiments that could be used to further test the model. © 2012 Elsevier Inc. Source


Popp F.,Ludwig Maximilians University of Munich | Armitage J.P.,Oxford Center for Integrative Systems Biology | Armitage J.P.,University of Oxford | Schuler D.,Ludwig Maximilians University of Munich
Nature Communications | Year: 2014

Most motile bacteria navigate within gradients of external chemical stimuli by regulating the length of randomly oriented swimming episodes. Magnetotactic bacteria are characterized by chains of intracellular ferromagnetic nanoparticles and their ability to sense the geomagnetic field, which is believed to facilitate directed motion, but is not well understood at the behavioural and molecular level. Here, we show that cells of Magnetospirillum gryphiswaldense unexpectedly display swimming polarity that depends on aerotactic signal transduction through one of its four chemotaxis operons (cheOp1). Growth of cells in magnetic fields superimposed on oxygen gradients results in a gradual inherited bias of swimming runs with one of the cell poles leading, such that the resulting overall swimming direction of entire populations can be reversed by changes in oxygen concentration. These findings clearly show that there is a direct molecular link between aerotactic sensing and the determination of magnetotactic polarity, through the sensory pathway, CheOp1. © 2014 Macmillan Publishers Limited. All rights reserved. Source


Murray P.J.,Mathematical Institute | Maini P.K.,Mathematical Institute | Maini P.K.,Oxford Center for Integrative Systems Biology | Baker R.E.,Mathematical Institute
Journal of Theoretical Biology | Year: 2011

The currently accepted interpretation of the clock and wavefront model of somitogenesis is that a posteriorly moving molecular gradient sequentially slows the rate of clock oscillations, resulting in a spatial readout of temporal oscillations. However, while molecular components of the clocks and wavefronts have now been identified in the pre-somitic mesoderm (PSM), there is not yet conclusive evidence demonstrating that the observed molecular wavefronts act to slow clock oscillations. Here we present an alternative formulation of the clock and wavefront model in which oscillator coupling, already known to play a key role in oscillator synchronisation, plays a fundamentally important role in the slowing of oscillations along the anterior-posterior (AP) axis. Our model has three parameters which can be determined, in any given species, by the measurement of three quantities: the clock period in the posterior PSM, somite length and the length of the PSM. A travelling wavefront, which slows oscillations along the AP axis, is an emergent feature of the model. Using the model we predict: (a) the distance between moving stripes of gene expression; (b) the number of moving stripes of gene expression and (c) the oscillator period profile along the AP axis. Predictions regarding the stripe data are verified using existing zebrafish data. We simulate a range of experimental perturbations and demonstrate how the model can be used to unambiguously define a reference frame along the AP axis. Comparing data from zebrafish, chick, mouse and snake, we demonstrate that: (a) variation in patterning profiles is accounted for by a single nondimensional parameter; the ratio of coupling strengths; and (b) the period profile along the AP axis is conserved across species. Thus the model is consistent with the idea that, although the genes involved in pattern propagation in the PSM vary, there is a conserved patterning mechanism across species. © 2011 Elsevier Ltd. Source


Obara B.,Oxford search Center | Fricker M.,University of Oxford | Gavaghan D.,Oxford Center for Integrative Systems Biology | Grau V.,University of Oxford
IEEE Transactions on Image Processing | Year: 2012

Many biomedical applications require detection of curvilinear structures in images and would benefit from automatic or semiautomatic segmentation to allow high-throughput measurements. Here, we propose a contrast-independent approach to identify curvilinear structures based on oriented phase congruency, i.e., the phase congruency tensor (PCT). We show that the proposed method is largely insensitive to intensity variations along the curve and provides successful detection within noisy regions. The performance of the PCT is evaluated by comparing it with state-of-the-art intensity-based approaches on both synthetic and real biological images. © 1992-2012 IEEE. Source


Schwarzlander M.,University of Oxford | Schwarzlander M.,University of Bonn | Logan D.C.,University of Saskatchewan | Johnston I.G.,Clarendon Laboratory | And 7 more authors.
Plant Cell | Year: 2012

Mitochondrial ATP synthesis is driven by a membrane potential across the inner mitochondrial membrane; this potential is generated by the proton-pumping electron transport chain. A balance between proton pumping and dissipation of the proton gradient by ATP-synthase is critical to avoid formation of excessive reactive oxygen species due to overreduction of the electron transport chain. Here, we report a mechanism that regulates bioenergetic balance in individual mitochondria: a transient partial depolarization of the inner membrane. Single mitochondria in living Arabidopsis thaliana root cells undergo sporadic rapid cycles of partial dissipation and restoration of membrane potential, as observed by real-time monitoring of the fluorescence of the lipophilic cationic dye tetramethyl rhodamine methyl ester. Pulsing is induced in tissues challenged by high temperature, H 2O 2, or cadmium. Pulses were coincident with a pronounced transient alkalinization of the matrix and are therefore not caused by uncoupling protein or by the opening of a nonspecific channel, which would lead to matrix acidification. Instead, a pulse is the result of Ca 2+ influx, which was observed coincident with pulsing; moreover, inhibitors of calcium transport reduced pulsing. We propose a role for pulsing as a transient uncoupling mechanism to counteract mitochondrial dysfunction and reactive oxygen species production. © 2012 American Society of Plant Biologists. All rights reserved. Source

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