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  1. AU="Alam Nazki, Aiman"
  2. AU="Schatteman, Isabelle"
  3. AU="Balzarini, Piera"
  4. AU="Tim Edwards Powers"
  5. AU="Nils Hartmann"
  6. AU="Simionescu, Maya"
  7. AU="Feng, Yicheng"
  8. AU="Roger Le Grand"
  9. AU="Tesfalidet, Solomon"
  10. AU="Geladari, Eleni"
  11. AU="Pallabi Mustafi"
  12. AU=Mountfort Katrina
  13. AU="Horne, Patrick"
  14. AU="Mhurchu, Cliona Ni"
  15. AU="Yatoo, Ali Mohd"
  16. AU="Zhang, Zhiru"
  17. AU="Hadie Adams"
  18. AU="Gaskin, Thomas R"
  19. AU="Guo, Chong"
  20. AU="Guocan Wang"
  21. AU="Catherine Crenn-Hebert"
  22. AU="Alistar, Cristina F"
  23. AU="Makhani, Sarah S"
  24. AU="Tayyeb Pourfallah"
  25. AU="Mauad, Thais"

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  1. Artikel ; Online: The interplay of spatial organization and biochemistry in building blocks of cellular signalling pathways.

    Krishnan, J / Lu, Lingjun / Alam Nazki, Aiman

    Journal of the Royal Society, Interface

    2020  Band 17, Heft 166, Seite(n) 20200251

    Abstract: Biochemical pathways and networks are central to cellular information processing. While a broad range of studies have dissected multiple aspects of information processing in biochemical pathways, the effect of spatial organization remains much less ... ...

    Abstract Biochemical pathways and networks are central to cellular information processing. While a broad range of studies have dissected multiple aspects of information processing in biochemical pathways, the effect of spatial organization remains much less understood. It is clear that space is central to intracellular organization, plays important roles in cellular information processing and has been exploited in evolution; additionally, it is being increasingly exploited in synthetic biology through the development of artificial compartments, in a variety of ways. In this paper, we dissect different aspects of the interplay between spatial organization and biochemical pathways, by focusing on basic building blocks of these pathways: covalent modification cycles and two-component systems, with enzymes which may be monofunctional or bifunctional. Our analysis of spatial organization is performed by examining a range of 'spatial designs': patterns of localization or non-localization of enzymes/substrates, theoretically and computationally. Using these well-characterized
    Mesh-Begriff(e) Biochemistry ; Computer Simulation ; Kinetics ; Synthetic Biology
    Sprache Englisch
    Erscheinungsdatum 2020-05-27
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2156283-0
    ISSN 1742-5662 ; 1742-5689
    ISSN (online) 1742-5662
    ISSN 1742-5689
    DOI 10.1098/rsif.2020.0251
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  2. Artikel ; Online: Spatial Control of Biochemical Modification Cascades and Pathways.

    Alam-Nazki, Aiman / Krishnan, J

    Biophysical journal

    2015  Band 108, Heft 12, Seite(n) 2912–2924

    Abstract: Information transmission in cells occurs through complex networks of proteins and genes and is relayed through cascades of biochemical modifications, which are typically studied through ordinary differential equations. However, it is becoming ... ...

    Abstract Information transmission in cells occurs through complex networks of proteins and genes and is relayed through cascades of biochemical modifications, which are typically studied through ordinary differential equations. However, it is becoming increasingly clear that spatial factors can strongly influence chemical information transmission in cells. In this article, we systematically disentangle the effects of space in signaling cascades. This is done by examining the effects of localization/compartmentalization and diffusion of enzymes and substrates in multiple variants of chemical modification cascades. This includes situations where the modified form of species at one stage 1) acts as an enzyme for the next stage; 2) acts as a substrate for the next stage; and 3) is involved in phosphotransfer. Our analysis reveals the multiple effects of space in signal transduction cascades. Although in some cases space plays a modulatory effect (itself of interest), in other cases, spatial regulation and control can profoundly affect the nature of information processing as a result of the subtle interplay between the patterns of localization of species, diffusion, and the nature of the modification cascades. Our results provide a platform for disentangling the role of space and spatial control in multiple cellular contexts and a basis for engineering spatial control in signaling cascades through localization/compartmentalization.
    Mesh-Begriff(e) Cell Compartmentation ; Metabolome ; Models, Theoretical ; Protein Processing, Post-Translational ; Signal Transduction
    Sprache Englisch
    Erscheinungsdatum 2015-06-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2015.05.012
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  3. Artikel ; Online: An investigation of spatial signal transduction in cellular networks

    Alam-Nazki Aiman / Krishnan J

    BMC Systems Biology, Vol 6, Iss 1, p

    2012  Band 83

    Abstract: Abstract Background Spatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to ... ...

    Abstract Abstract Background Spatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may play an important role in other apparently purely temporal signal transduction processes. It is increasingly being recognized that a conceptual basis for studying spatial signal transduction in signalling networks is necessary. Results In this work we examine spatial signal transduction in a series of standard motifs/networks. These networks include coherent and incoherent feedforward, positive and negative feedback, cyclic motifs, monostable switches, bistable switches and negative feedback oscillators. In all these cases, the driving signal has spatial variation. For each network we consider two cases, one where all elements are essentially non-diffusible, and the other where one of the network elements may be highly diffusible. A careful analysis of steady state signal transduction provides many insights into the behaviour of all these modules. While in the non-diffusible case for the most part, spatial signalling reflects the temporal signalling behaviour, in the diffusible cases, we see significant differences between spatial and temporal signalling characteristics. Our results demonstrate that the presence of diffusible elements in the networks provides important constraints and capabilities for signalling. Conclusions Our results provide a systematic basis for understanding spatial signalling in networks and the role of diffusible elements therein. This provides many insights into the signal transduction capabilities and constraints in such networks and suggests ways in which cellular signalling and information processing is organized to conform to or bypass those constraints. It also provides a framework for starting to understand the organization and regulation of spatial signal transduction in individual processes.
    Schlagwörter Cellular signal processing ; Spatial signalling ; Signalling motifs ; Global regulation ; Diffusion ; Non-linear dynamics ; Networks ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2012-07-01T00:00:00Z
    Verlag BioMed Central
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Covalent modification cycles through the spatial prism.

    Alam-Nazki, Aiman / Krishnan, J

    Biophysical journal

    2013  Band 105, Heft 7, Seite(n) 1720–1731

    Abstract: Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting ... ...

    Abstract Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting with a basic temporal cycle as a reference and focusing on steady-state signal transduction. We consider, in turn, the effect of diffusion on spatial signal transduction, spatial analogs of ultrasensitive behavior, and the interplay between enzyme localization and substrate diffusion. Our analysis reveals the need to explicitly account for kinetics and diffusional transport (and localization) of enzymes, substrates, and complexes. It demonstrates a complex and subtle interplay between spatial heterogeneity, diffusion, and localization. Overall, examining the spatial dimension of covalent modification reveals that 1), there are important differences between spatial and temporal signal transduction even in this cycle; and 2), spatial aspects may play a substantial role in affecting and distorting information transfer in modules/networks that are usually studied in purely temporal terms. This has important implications for the systematic understanding of signaling in covalent modification cycles, pathways, and networks in multiple cellular contexts.
    Mesh-Begriff(e) Diffusion ; Enzymes/metabolism ; Kinetics ; Models, Biological ; Protein Processing, Post-Translational ; Signal Transduction ; Substrate Cycling
    Chemische Substanzen Enzymes
    Sprache Englisch
    Erscheinungsdatum 2013-08-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2013.06.050
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  5. Artikel ; Online: An investigation of spatial signal transduction in cellular networks.

    Alam-Nazki, Aiman / Krishnan, J

    BMC systems biology

    2012  Band 6, Seite(n) 83

    Abstract: Background: Spatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may ... ...

    Abstract Background: Spatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may play an important role in other apparently purely temporal signal transduction processes. It is increasingly being recognized that a conceptual basis for studying spatial signal transduction in signalling networks is necessary.
    Results: In this work we examine spatial signal transduction in a series of standard motifs/networks. These networks include coherent and incoherent feedforward, positive and negative feedback, cyclic motifs, monostable switches, bistable switches and negative feedback oscillators. In all these cases, the driving signal has spatial variation. For each network we consider two cases, one where all elements are essentially non-diffusible, and the other where one of the network elements may be highly diffusible. A careful analysis of steady state signal transduction provides many insights into the behaviour of all these modules. While in the non-diffusible case for the most part, spatial signalling reflects the temporal signalling behaviour, in the diffusible cases, we see significant differences between spatial and temporal signalling characteristics. Our results demonstrate that the presence of diffusible elements in the networks provides important constraints and capabilities for signalling.
    Conclusions: Our results provide a systematic basis for understanding spatial signalling in networks and the role of diffusible elements therein. This provides many insights into the signal transduction capabilities and constraints in such networks and suggests ways in which cellular signalling and information processing is organized to conform to or bypass those constraints. It also provides a framework for starting to understand the organization and regulation of spatial signal transduction in individual processes.
    Mesh-Begriff(e) Cells/cytology ; Diffusion ; Feedback, Physiological ; Models, Biological ; Signal Transduction ; Systems Biology/methods
    Sprache Englisch
    Erscheinungsdatum 2012-07-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1752-0509
    ISSN (online) 1752-0509
    DOI 10.1186/1752-0509-6-83
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  6. Artikel ; Online: An investigation of design principles underlying repulsive and attractive gradient sensing and their switching.

    Krishnan, J / Alam-Nazki, Aiman

    Journal of theoretical biology

    2011  Band 273, Heft 1, Seite(n) 80–99

    Abstract: Many important cellular processes rely on cellular responses to spatially graded signals. This response may be either attractive, indicating a positive bias, or repulsive indicating a negative bias. In this paper we consider cells which exhibit both ... ...

    Abstract Many important cellular processes rely on cellular responses to spatially graded signals. This response may be either attractive, indicating a positive bias, or repulsive indicating a negative bias. In this paper we consider cells which exhibit both repulsive and attractive gradient sensing responses and aim to uncover the underlying design principles and features of how the networks are wired which could allow a cell to exhibit both responses. We use a modular approach to examine different configurations which will allow for a cell to exhibit both responses and analyse how this depends on the basic characteristics of gradient sensing and downstream signal propagation. Overall our analysis provides insights into how gradient responses can be switched and the key factors which affect this switching.
    Mesh-Begriff(e) Animals ; Models, Biological ; Signal Transduction
    Sprache Englisch
    Erscheinungsdatum 2011-03-21
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2010.11.046
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  7. Artikel: An investigation of design principles underlying repulsive and attractive gradient sensing and their switching

    Krishnan, J / Alam-Nazki, Aiman

    Journal of theoretical biology. 2011 Mar. 21, v. 273, no. 1

    2011  

    Abstract: Many important cellular processes rely on cellular responses to spatially graded signals. This response may be either attractive, indicating a positive bias, or repulsive indicating a negative bias. In this paper we consider cells which exhibit both ... ...

    Abstract Many important cellular processes rely on cellular responses to spatially graded signals. This response may be either attractive, indicating a positive bias, or repulsive indicating a negative bias. In this paper we consider cells which exhibit both repulsive and attractive gradient sensing responses and aim to uncover the underlying design principles and features of how the networks are wired which could allow a cell to exhibit both responses. We use a modular approach to examine different configurations which will allow for a cell to exhibit both responses and analyse how this depends on the basic characteristics of gradient sensing and downstream signal propagation. Overall our analysis provides insights into how gradient responses can be switched and the key factors which affect this switching.
    Schlagwörter cells ; physiological response ; signal transduction
    Sprache Englisch
    Erscheinungsverlauf 2011-0321
    Umfang p. 80-99.
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2010.11.046
    Datenquelle NAL Katalog (AGRICOLA)

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  8. Artikel ; Online: A mathematical modelling framework for understanding chemorepulsive signal transduction in Dictyostelium.

    Alam-Nazki, Aiman / Krishnan, J

    Journal of theoretical biology

    2010  Band 266, Heft 1, Seite(n) 140–153

    Abstract: Chemorepulsion is the process by which an organism or a cell moves in the direction of decreasing chemical concentration. While a few experimental studies have been performed, no mathematical models exist for this process. In this paper we have modelled ... ...

    Abstract Chemorepulsion is the process by which an organism or a cell moves in the direction of decreasing chemical concentration. While a few experimental studies have been performed, no mathematical models exist for this process. In this paper we have modelled gradient sensing, the first subprocess of chemorepulsion, in Dictyostelium discoideum-a well characterized model eukaryotic system. We take the first steps towards achieving a comprehensive mechanistic understanding of chemorepulsion in this system. We have used, as a basis, the biochemical network of the Keizer-Gunnink et al. (2007) to develop the mathematical modelling framework. This network describes the underlying pathways of chemorepellent gradient sensing in D. discoideum. Working within this modelling framework we address whether the postulated interactions of the pathways and species in this network can lead to a chemorepulsive response. We also analyse the possible role of additional regulatory effects (such as additional receptor regulation of enzymes in this network) and if this is necessary to achieve this behaviour. Thus we have investigated the receptor regulation of important enzymes and feedback effects in the network. This modelling framework generates important insights into and testable predictions regarding the role of key components and feedback loops in regulating chemorepulsive gradient sensing, and what factors might be important for generating a chemorepulsive response; it serves as a first step towards a comprehensive mechanistic understanding of this process.
    Mesh-Begriff(e) Actin Cytoskeleton/metabolism ; Algorithms ; Chemotaxis/physiology ; Computer Simulation ; Cyclic AMP/analogs & derivatives ; Cyclic AMP/metabolism ; Dictyostelium/physiology ; Diglycerides/metabolism ; Feedback, Physiological/physiology ; GTP-Binding Protein alpha Subunits/metabolism ; Models, Biological ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptors, Cyclic AMP/metabolism ; Signal Transduction/physiology ; Thionucleotides/metabolism ; Type C Phospholipases/metabolism
    Chemische Substanzen Diglycerides ; GTP-Binding Protein alpha Subunits ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositol Phosphates ; Receptors, Cyclic AMP ; Thionucleotides ; cyclic AMP receptor cAR1 ; phosphatidylinositol 3,4,5-triphosphate ; 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP (41941-66-6) ; Cyclic AMP (E0399OZS9N) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Type C Phospholipases (EC 3.1.4.-)
    Sprache Englisch
    Erscheinungsdatum 2010-09-07
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2010.05.017
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  9. Artikel: Covalent Modification Cycles through the Spatial Prism

    Alam-Nazki, Aiman / Krishnan, J

    Biophysical journal. 2013 Oct. 1, v. 105, no. 7

    2013  

    Abstract: Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting ... ...

    Abstract Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting with a basic temporal cycle as a reference and focusing on steady-state signal transduction. We consider, in turn, the effect of diffusion on spatial signal transduction, spatial analogs of ultrasensitive behavior, and the interplay between enzyme localization and substrate diffusion. Our analysis reveals the need to explicitly account for kinetics and diffusional transport (and localization) of enzymes, substrates, and complexes. It demonstrates a complex and subtle interplay between spatial heterogeneity, diffusion, and localization. Overall, examining the spatial dimension of covalent modification reveals that 1), there are important differences between spatial and temporal signal transduction even in this cycle; and 2), spatial aspects may play a substantial role in affecting and distorting information transfer in modules/networks that are usually studied in purely temporal terms. This has important implications for the systematic understanding of signaling in covalent modification cycles, pathways, and networks in multiple cellular contexts.
    Schlagwörter enzymes ; information exchange ; post-translational modification ; signal transduction
    Sprache Englisch
    Erscheinungsverlauf 2013-1001
    Umfang p. 1720-1731.
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2013.06.050
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  10. Artikel: Covalent Modification Cycles through the Spatial Prism

    Alam-Nazki, Aiman / Krishnan, J.

    Biophysical journal

    Band v. 105,, Heft no. 7

    Abstract: Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting ... ...

    Abstract Covalent modification cycles are basic units and building blocks of posttranslational modification and cellular signal transduction. We systematically explore different spatial aspects of signal transduction in covalent modification cycles by starting with a basic temporal cycle as a reference and focusing on steady-state signal transduction. We consider, in turn, the effect of diffusion on spatial signal transduction, spatial analogs of ultrasensitive behavior, and the interplay between enzyme localization and substrate diffusion. Our analysis reveals the need to explicitly account for kinetics and diffusional transport (and localization) of enzymes, substrates, and complexes. It demonstrates a complex and subtle interplay between spatial heterogeneity, diffusion, and localization. Overall, examining the spatial dimension of covalent modification reveals that 1), there are important differences between spatial and temporal signal transduction even in this cycle; and 2), spatial aspects may play a substantial role in affecting and distorting information transfer in modules/networks that are usually studied in purely temporal terms. This has important implications for the systematic understanding of signaling in covalent modification cycles, pathways, and networks in multiple cellular contexts.
    Schlagwörter post-translational modification ; signal transduction ; information exchange ; enzymes
    Sprache Englisch
    Dokumenttyp Artikel
    ISSN 0006-3495
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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