Imperial College London

DrRubenPerez-Carrasco

Faculty of Natural SciencesDepartment of Life Sciences

Lecturer in Theoretical Systems Biology
 
 
 
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Contact

 

r.perez-carrasco Website

 
 
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Location

 

303Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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32 results found

Lee HC, Hastings C, Oliveira NMM, PĂ©rez-Carrasco R, Page KM, Wolpert L, Stern CDet al., 2022, "Neighbourhood watch" model: embryonic epiblast cells assess positional information in relation to their neighbours., Development

In many developing and regenerating systems, tissue pattern is established through gradients of informative morphogens, but we know little about how cells interpret these. Using experimental manipulation of early chick embryos including misexpression of an inducer (VG1 or ACTIVIN) and an inhibitor (BMP4), we test two alternative models for their ability to explain how the site of primitive streak formation is positioned relative to the rest of the embryo. In one model, cells read morphogen concentrations cell-autonomously. In the other, cells sense changes in morphogen status relative to their neighbourhood. We find that only the latter model can account for the experimental results, including some counter-intuitive predictions. This mechanism (which we name "neighbourhood watch" model) illuminates the classic "French Flag Problem" and how positional information is interpreted by a sheet of cells in a large developing system.

Journal article

Perez-Carrasco R, Franco-Onate M-J, Walter J-C, Dorignac J, Geniet F, Palmeri J, Parmeggiani A, Walliser N-O, Nord ALet al., 2022, Relaxation time asymmetry in stator dynamics of the bacterial flagellar motor, SCIENCE ADVANCES, Vol: 8, ISSN: 2375-2548

Journal article

Perez-Carrasco R, Franco-Onate M-J, Walter J-C, Dorignac J, Geniet F, Palmeri J, Parmeggiani A, Walliser N-O, Nord ALet al., 2022, Stator dynamics of the bacterial flagellar motor, Publisher: CELL PRESS, Pages: 2-2, ISSN: 0006-3495

Conference paper

Verd B, Perez-Carrasco R, 2021, Interdisciplinary approaches to dynamics in biology, INTERFACE FOCUS, Vol: 11, ISSN: 2042-8898

Journal article

Exelby K, Herrera-Delgado E, Perez LG, Perez-Carrasco R, Sagner A, Metzis V, Sollich P, Briscoe Jet al., 2021, Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks, DEVELOPMENT, Vol: 148, ISSN: 0950-1991

Journal article

Rayon T, Stamataki D, Perez-Carrasco R, Garcia-Perez L, Barrington C, Melchionda M, Exelby K, Lazaro J, Tybulewicz VLJ, Fisher EMC, Briscoe Jet al., 2020, Species-specific pace of development is associated with differences in protein stability, Science, Vol: 369, Pages: 1-15, ISSN: 0036-8075

INTRODUCTIONWhat determines the pace of embryonic development? Although the molecular and cellular mechanisms of many developmental processes are evolutionarily conserved, the pace at which these operate varies considerably between species. The tempo of embryonic development controls the rate of individual differentiation processes and determines the overall duration of development. Despite its importance, however, the mechanisms that control developmental tempo remain elusive.RATIONALEComparing highly conserved and well-characterized developmental processes in different species permits a search for mechanisms that explain differences in tempo. The specification of neuronal subtype identity in the vertebrate spinal cord is a prominent example, lasting less than a day in zebrafish, 3 to 4 days in mouse, and around 2 weeks in human. The development of the spinal cord involves a well-defined gene regulatory program comprising a series of stereotypic changes in gene expression, regulated by extrinsic signaling as cells differentiate from neural progenitors to postmitotic neurons. The regulatory program and resulting neuronal cell types are highly similar in different vertebrates, despite the difference in tempo between species. We therefore set out to characterize the pace of differentiation of one specific neuronal subtype—motor neurons—in human and mouse and to identify molecular differences that explain differences in pace. To this end, we took advantage of the in vitro recapitulation of in vivo developmental programs using the directed differentiation of human and mouse embryonic stem cells.RESULTSWe found that all stages of the developmental progression from neural progenitor to motor neuron were proportionally prolonged in human compared with mouse, resulting in human motor neuron differentiation taking about 2.5 times longer than mouse. Differences in tempo were not due to differences in the sensitivity of cells to signals, nor could they be attribute

Journal article

Perez-Carrasco R, Beentjes C, Grima R, 2020, Effects of cell cycle variability on lineage and population measurements of messenger RNA abundance, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 17, ISSN: 1742-5689

Journal article

Barbier I, Perez-Carrasco R, Schaerli Y, 2020, Controlling spatiotemporal pattern formation in a concentration gradient with a synthetic toggle switch, MOLECULAR SYSTEMS BIOLOGY, Vol: 16, ISSN: 1744-4292

Journal article

Beentjes CHL, Perez-Carrasco R, Grima R, 2020, Exact solution of stochastic gene expression models with bursting, cell cycle and replication dynamics, PHYSICAL REVIEW E, Vol: 101, ISSN: 2470-0045

Journal article

Rayon T, Stamataki D, Perez-Carrasco R, Garcia-Perez L, Barrington C, Melchionda M, Exelby K, Tybulewicz V, Fisher EMC, Briscoe Jet al., 2019, Species-specific developmental timing is associated with global differences in protein stability in mouse and human

<jats:title>ABSTRACT</jats:title><jats:p>What determines the pace of embryonic development? Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which these operate can vary substantially between species. For example, the same genetic programme, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the programme runs twice as fast in mouse as in human. We provide evidence that this is neither due to differences in signalling, nor the genomic sequence of genes or their regulatory elements. Instead, we find an approximately two-fold increase in protein stability and cell cycle duration in human cells compared to mouse. This can account for the slower pace of human development, indicating that global differences in key kinetic parameters play a major role in interspecies differences in developmental tempo.</jats:p>

Journal article

Guerrero P, Perez-Carrasco R, Zagorski M, Page D, Kicheva A, Briscoe J, Page KMet al., 2019, Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium, DEVELOPMENT, Vol: 146, ISSN: 0950-1991

Journal article

Exelby K, Herrera-Delgado E, Perez LG, Perez-Carrasco R, Sagner A, Metzis V, Sollich P, Briscoe Jet al., 2019, Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks

<jats:title>Abstract</jats:title><jats:p>During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.</jats:p>

Journal article

Folguera-Blasco N, Perez-Carrasco R, Cuyas E, Menendez JA, Alarcon Tet al., 2019, A multiscale model of epigenetic heterogeneity-driven cell fate decision-making, PLOS COMPUTATIONAL BIOLOGY, Vol: 15

Journal article

de la Cruz R, Perez-Carrasco R, Guerrero P, Alarcon T, Page KMet al., 2019, de la Cruz et al. Reply., Phys Rev Lett, Vol: 122

Journal article

Page KM, Perez-Carrasco R, 2018, Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 15, ISSN: 1742-5689

Journal article

Perez-Carrasco R, Barnes CP, Schaerli Y, Isalan M, Briscoe J, Page KMet al., 2018, Combining a toggle switch and a repressilator within the AC-DC circuit generates distinct dynamical behaviors, Cell Systems, Vol: 6, Pages: 521-530.e3, ISSN: 2405-4712

Although the structure of a genetically encoded regulatory circuit is an important determinant of its function, the relationship between circuit topology and the dynamical behaviors it can exhibit is not well understood. Here, we explore the range of behaviors available to the AC-DC circuit. This circuit consists of three genes connected as a combination of a toggle switch and a repressilator. Using dynamical systems theory, we show that the AC-DC circuit exhibits both oscillations and bistability within the same region of parameter space; this generates emergent behaviors not available to either the toggle switch or the repressilator alone. The AC-DC circuit can switch on oscillations via two distinct mechanisms, one of which induces coherence into ensembles of oscillators. In addition, we show that in the presence of noise, the AC-DC circuit can behave as an excitable system capable of spatial signal propagation or coherence resonance. Together, these results demonstrate how combinations of simple motifs can exhibit multiple complex behaviors.

Journal article

de la Cruz R, Perez-Carrasco R, Guerrero P, Alarcon T, Page KMet al., 2018, Minimum Action Path Theory Reveals the Details of Stochastic Transitions Out of Oscillatory States, PHYSICAL REVIEW LETTERS, Vol: 120, ISSN: 0031-9007

Journal article

Herrera-Delgado E, Perez-Carrasco R, Briscoe J, Sollich Pet al., 2018, Memory functions reveal structural properties of gene regulatory networks, PLOS COMPUTATIONAL BIOLOGY, Vol: 14

Journal article

Nord AL, Gachon E, Perez-Carrasco R, Nirody JA, Barducci A, Berry RM, Pedaci Fet al., 2017, Catch bond drives stator mechanosensitivity in the bacterial flagellar motor, Proceedings of the National Academy of Sciences of the United States of America, Vol: 114, Pages: 12952-12957, ISSN: 0027-8424

The bacterial flagellar motor (BFM) is the rotary motor that rotates each bacterial flagellum, powering the swimming and swarming of many motile bacteria. The torque is provided by stator units, ion motive force-powered ion channels known to assemble and disassemble dynamically in the BFM. This turnover is mechanosensitive, with the number of engaged units dependent on the viscous load experienced by the motor through the flagellum. However, the molecular mechanism driving BFM mechanosensitivity is unknown. Here, we directly measure the kinetics of arrival and departure of the stator units in individual motors via analysis of high-resolution recordings of motor speed, while dynamically varying the load on the motor via external magnetic torque. The kinetic rates obtained, robust with respect to the details of the applied adsorption model, indicate that the lifetime of an assembled stator unit increases when a higher force is applied to its anchoring point in the cell wall. This provides strong evidence that a catch bond (a bond strengthened instead of weakened by force) drives mechanosensitivity of the flagellar motor complex. These results add the BFM to a short, but growing, list of systems demonstrating catch bonds, suggesting that this “molecular strategy” is a widespread mechanism to sense and respond to mechanical stress. We propose that force-enhanced stator adhesion allows the cell to adapt to a heterogeneous environmental viscosity and may ultimately play a role in surface-sensing during swarming and biofilm formation.

Journal article

Perez-Carrasco R, Guerrero P, Briscoe J, Page KMet al., 2016, Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches, PLOS COMPUTATIONAL BIOLOGY, Vol: 12

Journal article

Woods ML, Leon M, Perez-Carrasco R, Barnes CPet al., 2016, A Statistical Approach Reveals Designs for the Most Robust Stochastic Gene Oscillators, ACS SYNTHETIC BIOLOGY, Vol: 5, Pages: 459-470, ISSN: 2161-5063

Journal article

Bodnar M, Guerrero P, Perez-Carrasco R, Piotrowska MJet al., 2016, Deterministic and Stochastic Study for a Microscopic Angiogenesis Model: Applications to the Lewis Lung Carcinoma, PLOS ONE, Vol: 11, ISSN: 1932-6203

Journal article

Cohen M, Page KM, Perez-Carrasco R, Barnes CP, Briscoe Jet al., 2016, Mathematical models help explain experimental data. Response to 'Transcriptional interpretation of Shh morphogen signaling: computational modeling validates empirically established models', DEVELOPMENT, Vol: 143, Pages: 1640-1643, ISSN: 0950-1991

Journal article

Cohen M, Page KM, Perez-Carrasco R, Barnes CP, Briscoe Jet al., 2014, A theoretical framework for the regulation of Shh morphogen-controlled gene expression, DEVELOPMENT, Vol: 141, Pages: 3868-3878, ISSN: 0950-1991

Journal article

Perez-Carrasco R, Sancho JM, 2013, Theoretical study of a molecular turbine, PHYSICAL REVIEW E, Vol: 88, ISSN: 1539-3755

Journal article

Perez-Carrasco R, Fiasconaro A, Falo F, Sancho JMet al., 2013, Modeling the mechanochemistry of the phi 29 DNA translocation motor, PHYSICAL REVIEW E, Vol: 87, ISSN: 1539-3755

Journal article

Perez-Carrasco R, Sancho JM, 2012, Physics of molecular machines operated by a particle flux, EPL, Vol: 100, ISSN: 0295-5075

Journal article

Sancho JM, Perez-Carrasco R, 2012, POWER AND EFFICIENCY OF F1-ATPase MOLECULAR MOTOR, FLUCTUATION AND NOISE LETTERS, Vol: 11, ISSN: 0219-4775

Journal article

Perez-Carrasco R, Sancho JM, 2011, Molecular motors in conservative and dissipative regimes, PHYSICAL REVIEW E, Vol: 84, ISSN: 1539-3755

Journal article

Perez-Carrasco R, Sancho JM, 2010, Fokker-Planck approach to molecular motors, EPL, Vol: 91, ISSN: 0295-5075

Journal article

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