Research Topics
| Pablo A IglesiasSummaryAffiliation: Johns Hopkins University Country: USA Publications
Research Grants
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Detail Information
Publications
Quantifying robustness of biochemical network modelsLan Ma
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD USA
BMC Bioinformatics 3:38. 2002..Robustness of mathematical models of biochemical networks is important for validation purposes and can be used as a means of selecting between different competing models. Tools for quantifying parametric robustness are needed...
Biased excitable networks: how cells direct motion in response to gradientsPablo A Iglesias
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, United States
Curr Opin Cell Biol 24:245-53. 2012..In this review, we discuss some of these observations and theories proposed to explain them. We also suggest a mechanism for cell polarity that can be incorporated into the existing framework...
Chemoattractant signaling in dictyostelium: adaptation and amplificationPablo A Iglesias
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA
Sci Signal 5:pe8. 2012..Recent quantitative experiments provide support for a popular model: the local excitation, global inhibition mechanism of gradient sensing. Here, I discuss these findings and suggest some important open problems...
A method for determining the robustness of bio-molecular oscillator modelsReza Ghaemi
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA
BMC Syst Biol 3:95. 2009..Several tools have been proposed in the literature. Unfortunately, multiparameter robustness analysis suffers from computational limitations...
Spatial regulation of PI3K signaling during chemotaxisPablo A Iglesias
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA
Wiley Interdiscip Rev Syst Biol Med 1:247-53. 2009..We also briefly discuss one model used to elucidate the PI3K pathway...
A systems biology view of adaptation in sensory mechanismsPablo A Iglesias
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
Adv Exp Med Biol 736:499-516. 2012..While most of these models have been used to study chemoattractant-induced responses in bacteria and amoebae, the system-theoretic issues associated with these systems are of importance in a broad spectrum of biological systems...
Navigating through models of chemotaxisPablo A Iglesias
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Curr Opin Cell Biol 20:35-40. 2008..Mathematical models that have been proposed to explain chemotaxis typically focus on only one of these processes. We summarize the strengths and weaknesses of the models and point out the need for an integrated model...
tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxisLinnan Tang
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Genes Dev 22:2278-90. 2008..Thus, localization of kinase activity to microtubules is critical for TsuA function. We propose that functions in association with the microtubule network may underlie the divergent roles of Fused kinase proteins in different organisms...
Automated characterization of cell shape changes during amoeboid motility by skeletonizationYuan Xiong
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
BMC Syst Biol 4:33. 2010....
Two complementary, local excitation, global inhibition mechanisms acting in parallel can explain the chemoattractant-induced regulation of PI(3,4,5)P3 response in dictyostelium cellsLan Ma
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA
Biophys J 87:3764-74. 2004..Finally, we use the model to predict the response of a cell where only a fraction is stimulated by a saturating dose of chemoattractant...
A mechanosensory system governs myosin II accumulation in dividing cellsYee Seir Kee
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Biol Cell 23:1510-23. 2012..Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow...
Deconvolution of the cellular force-generating subsystems that govern cytokinesis furrow ingressionChristopher C Poirier
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America
PLoS Comput Biol 8:e1002467. 2012..Our simulations highlight the relative contributions of different biomechanical subsystems to cell shape progression during cell division...
Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensationTianzhi Luo
Department of Cell Biology, The Johns Hopkins University, Baltimore, Maryland, USA
Biophys J 102:238-47. 2012..This mechanism is likely to be general for a range of myosin II-dependent cellular mechanosensory processes...
Dynacortin facilitates polarization of chemotaxing cellsCathryn Kabacoff
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
BMC Biol 5:53. 2007..Dynacortin also becomes highly enriched in cortical protrusions, which are sites of new actin assembly...
Mitotic membrane helps to focus and stabilize the mitotic spindleChristopher C Poirier
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD, USA
Biophys J 99:3182-90. 2010..We show that an elastic membrane around the mitotic apparatus helps to focus MT minus ends and provides a resistive force that acts antagonistically to plus-end-directed MT motors such as Eg5...
Mechanosensing through cooperative interactions between myosin II and the actin crosslinker cortexillin IYixin Ren
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Curr Biol 19:1421-8. 2009..For a myosin motor to experience tension, the actin filament must also be anchored...
PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxisYoichiro Kamimura
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
Curr Biol 18:1034-43. 2008..However, chemotaxis can still occur in the absence of PIP(3), and the identities of the PIP(3)-independent pathways remain unknown...
Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeletonChris Janetopoulos
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 101:8951-6. 2004..These results support a local excitation/global inhibition model and argue against other schemes proposed to explain directional sensing...
Modeling cellular deformations using the level set formalismLiu Yang
Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
BMC Syst Biol 2:68. 2008..Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM), in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries...
An information-theoretic characterization of the optimal gradient sensing response of cellsBurton W Andrews
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, Maryland, United States of America
PLoS Comput Biol 3:e153. 2007..Our results demonstrate that different observed classes of responses in cells (polarized and unpolarized) are optimal under varying information assumptions...
Regulation of SREBP during hypoxia requires Ofd1-mediated control of both DNA binding and degradationJoshua R Porter
Department of Electrical and Computer Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Biol Cell 23:3764-74. 2012..This model quantifies our understanding of a novel oxygen-sensing mechanism that is widely conserved...
PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxisLingfeng Chen
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
Dev Cell 12:603-14. 2007..We propose that PLA(2) and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA(2) may be important mediators of the response...
Tools for analyzing cell shape changes during chemotaxisYuan Xiong
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
Integr Biol (Camb) 2:561-7. 2010..Here we review recent developments in the tracking and understanding of motile chemotaxing cells, with a particular emphasis on the description of pseudopodial activity in chemotactic Dictyostelium cells...
Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanicsElizabeth M Reichl
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Curr Biol 18:471-80. 2008..Discerning how this integrated network operates is essential for understanding cytokinesis contractility and shape control. Here, we analyzed the cytoskeletal network that drives furrow ingression in Dictyostelium...
A framework for designing and analyzing binary decision-making strategies in cellular systemsJoshua R Porter
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
Integr Biol (Camb) 4:310-7. 2012..As proof of concept, we use the framework to quantify the goals of the externally triggered apoptosis pathway...
Identifying a static nonlinear structure in a biological system using noisy, sparse dataJoshua R Porter
Department of Electrical and Computer Engineering, Johns Hopkins University, 105 Barton Hall, 3400 N Charles Street, Baltimore, MD 21218, USA
J Theor Biol 300:232-41. 2012..Simulations with this model produced outputs consistent with experimental observations. The techniques introduced here will provide researchers with a new tool by which biological systems can be identified and characterized...
Chemoattractant signaling in dictyostelium discoideumCarol L Manahan
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Annu Rev Cell Dev Biol 20:223-53. 2004..The modules and connections represent current understanding, and future information is expected to modify and build upon this structure...
A mechanosensory system controls cell shape changes during mitosisJanet C Effler
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cell Cycle 6:30-5. 2007..In this review, we summarize these findings and their implications for cytokinesis regulation and for understanding the cytoskeletal system architecture that governs shape control...
14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesisQiongqiong Zhou
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Curr Biol 20:1881-9. 2010..However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system...
Spatial regulation improves antiparallel microtubule overlap during mitotic spindle assemblyWilbur E Channels
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA
Biophys J 94:2598-609. 2008..Finally, we show that limiting the diffusion of motor complexes within the spindle region increases antiparallel microtubule interaction...
Cells navigate with a local-excitation, global-inhibition-biased excitable networkYuan Xiong
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Proc Natl Acad Sci U S A 107:17079-86. 2010..Our study brings together heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli, and spatial gradient sensing into a unified scheme...
Dynamic properties of network motifs contribute to biological network organizationRobert J Prill
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA
PLoS Biol 3:e343. 2005..We propose that robust dynamical stability is an influential property that can determine the non-random structure of biological networks...
Separation anxiety: stress, tension and cytokinesisKrithika Mohan
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
Exp Cell Res 318:1428-34. 2012..We also describe a mechanosensory feedback control system that regulates protein localization and shape progression during cytokinesis...
Lineage mapping the pre-implantation mouse embryo by two-photon microscopy, new insights into the segregation of cell fatesKatie McDole
Department of Biology, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA
Dev Biol 355:239-49. 2011..Our studies provide a framework for the future use of specific markers to track cell fate molecularly and with high accuracy...
Local excitation, global inhibition mechanism for gradient sensing: an interactive appletBrett Kutscher
Department of Electrical and Computer Engineering, Johns Hopkins University, 3400 North Charles Street, 226 Barton Hall, Baltimore, MD 21218, USA
Sci STKE 2004:pl3. 2004..To illustrate this general mechanism, we have developed an interactive applet that mimics laboratory experiments in which either spatially homogeneous or heterogeneous stimuli of chemoattractant are applied...
Coordination of chromosome alignment and mitotic progression by the chromosome-based Ran signalHoi Y Li
Department of Embryology, Carnegie Institution of Washington and Howard Hughes Medical Institute, Baltimore, Maryland, USA
Cell Cycle 6:1886-95. 2007..Our spatial simulation of RanGTP production using individual chromosomes should provide means to further understand how the Ran system and the cell cycle machinery coordinately regulate mitosis...
Optimal noise filtering in the chemotactic response of Escherichia coliBurton W Andrews
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America
PLoS Comput Biol 2:e154. 2006..This paper furnishes a simple quantitative framework for interpreting many of the key notions about bacterial chemotaxis, and, more generally, it highlights the constraints on biological systems imposed by noise...
MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeastSaurabh Paliwal
Department of Biomedical Engineering and Whitaker Institute of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA
Nature 446:46-51. 2007..In addition, the dynamic range of gradient sensing of Kss1-deficient cells was reduced compared with wild type. We thus provide unsuspected functional significance for this kinase in regulation of the mating response...
Mitosis-specific mechanosensing and contractile-protein redistribution control cell shapeJanet C Effler
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA
Curr Biol 16:1962-7. 2006..Our data provide evidence for a mechanosensory system that directs contractile proteins to regulate cell shape during mitosis...
Modeling spatial and temporal dynamics of chemotactic networksLiu Yang
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD, USA
Methods Mol Biol 571:489-505. 2009..Computer simulations have proved to be useful in testing conceptual models. Here we outline the steps required to develop these models...
Nucleating new branches from oldYixian Zheng
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA
Cell 152:669-70. 2013..Using total internal reflection fluorescent microscopy and Xenopus egg extracts, Petry et al. demonstrate that new microtubules can also nucleate and branch out from existing ones in animal cells...
Bringing the physical sciences into your cell biology researchDouglas N Robinson
Department of Cell Biology and Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Biol Cell 23:4167-70. 2012..This effort requires an interdisciplinary approach by investigators from both the biological and the physical sciences...
An integrative approach to understanding mechanosensationChristopher C Poirier
Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400North Charles Street, Baltimore, MD 21218, USA
Brief Bioinform 8:258-65. 2007..Multiscale modeling methods combined with experimental techniques in an integrative approach are suggested as ways of undertaking the study of such systems...
Ergosterol regulates sterol regulatory element binding protein (SREBP) cleavage in fission yeastJoshua R Porter
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA
J Biol Chem 285:41051-61. 2010..Based on this relationship, we predict that the Sre1-Scp1 complex exists under "active" and "inactive" states and that the transition between these states is cooperatively mediated by ergosterol...
Modeling the cell's guidance systemPablo A Iglesias
Department of Electrical and Computer Engineering, Johns Hopkins University, 105 Barton Hall, Baltimore, MD 21218, USA
Sci STKE 2002:RE12. 2002..We also propose a way to view chemotaxis regulation as a highly coupled combination of semi-independent control modules, leading to simplifying modeling of this complex cellular behavior...
Control analysis of bacterial chemotaxis signalingTau Mu Yi
Department of Developmental and Cell Biology, Center for Complex Biological Systems, Irvine, California, USA
Methods Enzymol 422:123-40. 2007..This chapter describes some basic principles of control theory relevant to the analysis of this sensing system, including sensitivity analysis, Bode plots, integral feedback control, and noise filters (i.e., Kalman filters)...
Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophilsAndre Levchenko
Divisions of Biology, California Institute of Technology, Pasadena, California 91125, USA
Biophys J 82:50-63. 2002..We propose that the underlying principles of perfect adaptation and substrate supply-based positive feedback will be found in the sensory systems of other chemotactic cell types...
Research Grants
- Modeling of chemotactic sensing in DictyosteliumPablo Iglesias; Fiscal Year: 2007....
- Computational Models of Cell DivisionDouglas N Robinson; Fiscal Year: 2010..In this research we combine computational and experimental tools to study the way that cells regulate their mechanical properties to ensure that each mother cells successfully divides into two equally-sized daughter cells. ..
