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  1. Article ; Online: In their own words: Interviews with Cell Cycle. John J. Tyson on his highly cited paper.

    Tyson, John J

    Cell cycle (Georgetown, Tex.)

    2009  Volume 8, Issue 20, Page(s) 3261

    MeSH term(s) Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Feedback ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-mdm2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Cell Cycle Proteins ; DNA-Binding Proteins ; Tumor Suppressor Protein p53 ; Tumor Suppressor Proteins ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2009-10-08
    Publishing country United States
    Document type Interview ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.8.20.10189
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  2. Article ; Online: The bistable mitotic switch in fission yeast.

    Novák, Béla / Tyson, John J

    Molecular biology of the cell

    2024  , Page(s) mbcE24030142

    Abstract: In favorable conditions, eukaryotic cells proceed irreversibly through the cell division cycle (G1-S-G2-M) in order to produce two daughter cells with the same number and identity of chromosomes of their progenitor. The integrity of this process is ... ...

    Abstract In favorable conditions, eukaryotic cells proceed irreversibly through the cell division cycle (G1-S-G2-M) in order to produce two daughter cells with the same number and identity of chromosomes of their progenitor. The integrity of this process is maintained by 'checkpoints' that hold a cell at particular transition points of the cycle until all requisite events are completed. The crucial functions of these checkpoints seem to depend on irreversible bistability of the underlying checkpoint control systems. Bistability of cell cycle transitions has been confirmed experimentally in frog egg extracts, budding yeast cells and mammalian cells. For fission yeast cells, a recent paper by Patterson et al. (2021) provides experimental evidence for an abrupt transition from G2 phase into mitosis, and we show that these data are consistent with a stochastic model of a bistable switch governing the G2/M checkpoint. Interestingly, our model suggests that their experimental data could also be explained by a reversible/sigmoidal switch, and stochastic simulations confirm this supposition. We propose a simple modification of their experimental protocol that could provide convincing evidence for (or against) bistability of the G2/M transition in fission yeast.
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E24-03-0142
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  3. Article ; Online: From the Belousov-Zhabotinsky reaction to biochemical clocks, traveling waves and cell cycle regulation.

    Tyson, John J

    The Biochemical journal

    2022  Volume 479, Issue 2, Page(s) 185–206

    Abstract: In the last 20 years, a growing army of systems biologists has employed quantitative experimental methods and theoretical tools of data analysis and mathematical modeling to unravel the molecular details of biological control systems with novel studies ... ...

    Abstract In the last 20 years, a growing army of systems biologists has employed quantitative experimental methods and theoretical tools of data analysis and mathematical modeling to unravel the molecular details of biological control systems with novel studies of biochemical clocks, cellular decision-making, and signaling networks in time and space. Few people know that one of the roots of this new paradigm in cell biology can be traced to a serendipitous discovery by an obscure Russian biochemist, Boris Belousov, who was studying the oxidation of citric acid. The story is told here from an historical perspective, tracing its meandering path through glycolytic oscillations, cAMP signaling, and frog egg development. The connections among these diverse themes are drawn out by simple mathematical models (nonlinear differential equations) that share common structures and properties.
    MeSH term(s) Amoeba/metabolism ; Animals ; Anura/embryology ; Biological Clocks/physiology ; Cell Cycle Checkpoints/physiology ; Citric Acid ; Cyclic AMP/metabolism ; Glycolysis/physiology ; Models, Biological ; Ovum/growth & development ; Oxidation-Reduction ; Signal Transduction/physiology ; Systems Biology/methods ; Yeasts/metabolism
    Chemical Substances Citric Acid (2968PHW8QP) ; Cyclic AMP (E0399OZS9N)
    Language English
    Publishing date 2022-02-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20210370
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  4. Article: Evolutionary Stability of Small Molecular Regulatory Networks That Exhibit Near-Perfect Adaptation.

    Singhania, Rajat / Tyson, John J

    Biology

    2023  Volume 12, Issue 6

    Abstract: Large-scale protein regulatory networks, such as signal transduction systems, contain small-scale modules ('motifs') that carry out specific dynamical functions. Systematic characterization of the properties of small network motifs is therefore of great ... ...

    Abstract Large-scale protein regulatory networks, such as signal transduction systems, contain small-scale modules ('motifs') that carry out specific dynamical functions. Systematic characterization of the properties of small network motifs is therefore of great interest to molecular systems biologists. We simulate a generic model of three-node motifs in search of near-perfect adaptation, the property that a system responds transiently to a change in an environmental signal and then returns near-perfectly to its pre-signal state (even in the continued presence of the signal). Using an evolutionary algorithm, we search the parameter space of these generic motifs for network topologies that score well on a pre-defined measure of near-perfect adaptation. We find many high-scoring parameter sets across a variety of three-node topologies. Of all possibilities, the highest scoring topologies contain incoherent feed-forward loops (IFFLs), and these topologies are evolutionarily stable in the sense that, under 'macro-mutations' that alter the topology of a network, the IFFL motif is consistently maintained. Topologies that rely on negative feedback loops with buffering (NFLBs) are also high-scoring; however, they are not evolutionarily stable in the sense that, under macro-mutations, they tend to evolve an IFFL motif and may-or may not-lose the NFLB motif.
    Language English
    Publishing date 2023-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology12060841
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  5. Article ; Online: Turing-pattern model of scaffolding proteins that establish spatial asymmetry during the cell cycle of

    Xu, Chunrui / Tyson, John J / Cao, Yang

    iScience

    2023  Volume 26, Issue 4, Page(s) 106513

    Abstract: The crescent-shaped ... ...

    Abstract The crescent-shaped bacterium
    Language English
    Publishing date 2023-03-29
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106513
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  6. Article ; Online: Mitotic kinase oscillation governs the latching of cell cycle switches.

    Novak, Bela / Tyson, John J

    Current biology : CB

    2022  Volume 32, Issue 12, Page(s) 2780–2785.e2

    Abstract: In 1996, Kim ... ...

    Abstract In 1996, Kim Nasmyth
    MeSH term(s) Cell Cycle ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Mitosis ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Saccharomycetales/metabolism
    Chemical Substances Cell Cycle Proteins ; Saccharomyces cerevisiae Proteins ; Cyclin-Dependent Kinases (EC 2.7.11.22)
    Language English
    Publishing date 2022-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2022.04.016
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  7. Article ; Online: Evolutionary Stability of Small Molecular Regulatory Networks That Exhibit Near-Perfect Adaptation

    Rajat Singhania / John J. Tyson

    Biology, Vol 12, Iss 841, p

    2023  Volume 841

    Abstract: Large-scale protein regulatory networks, such as signal transduction systems, contain small-scale modules (‘motifs’) that carry out specific dynamical functions. Systematic characterization of the properties of small network motifs is therefore of great ... ...

    Abstract Large-scale protein regulatory networks, such as signal transduction systems, contain small-scale modules (‘motifs’) that carry out specific dynamical functions. Systematic characterization of the properties of small network motifs is therefore of great interest to molecular systems biologists. We simulate a generic model of three-node motifs in search of near-perfect adaptation, the property that a system responds transiently to a change in an environmental signal and then returns near-perfectly to its pre-signal state (even in the continued presence of the signal). Using an evolutionary algorithm, we search the parameter space of these generic motifs for network topologies that score well on a pre-defined measure of near-perfect adaptation. We find many high-scoring parameter sets across a variety of three-node topologies. Of all possibilities, the highest scoring topologies contain incoherent feed-forward loops (IFFLs), and these topologies are evolutionarily stable in the sense that, under ‘macro-mutations’ that alter the topology of a network, the IFFL motif is consistently maintained. Topologies that rely on negative feedback loops with buffering (NFLBs) are also high-scoring; however, they are not evolutionarily stable in the sense that, under macro-mutations, they tend to evolve an IFFL motif and may—or may not—lose the NFLB motif.
    Keywords perfect adaptation ; molecular regulatory networks ; evolutionary algorithm ; evolutionary stability ; incoherent feedforward loops ; Biology (General) ; QH301-705.5
    Subject code 006
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Time-keeping and decision-making in the cell cycle.

    Tyson, John J / Novák, Béla

    Interface focus

    2022  Volume 12, Issue 4, Page(s) 20210075

    Abstract: Cell growth, DNA replication, mitosis and division are the fundamental processes by which life is passed on from one generation of eukaryotic cells to the next. The eukaryotic cell cycle is intrinsically a periodic process but not so much a 'clock' as a ' ...

    Abstract Cell growth, DNA replication, mitosis and division are the fundamental processes by which life is passed on from one generation of eukaryotic cells to the next. The eukaryotic cell cycle is intrinsically a periodic process but not so much a 'clock' as a 'copy machine', making new daughter cells as warranted. Cells growing under ideal conditions divide with clock-like regularity; however, if they are challenged with DNA-damaging agents or mitotic spindle disrupters, they will not progress to the next stage of the cycle until the damage is repaired. These 'decisions' (to exit and re-enter the cell cycle) are essential to maintain the integrity of the genome from generation to generation. A crucial challenge for molecular cell biologists in the 1990s was to unravel the genetic and biochemical mechanisms of cell cycle control in eukaryotes. Central to this effort were biochemical studies of the clock-like regulation of 'mitosis promoting factor' during synchronous mitotic cycles of fertilized frog eggs and genetic studies of the switch-like regulation of 'cyclin-dependent kinases' in yeast cells. In this review, we uncover some secrets of cell cycle regulation by mathematical modelling of increasingly more complex molecular regulatory networks of cell cycle 'clocks' and 'switches'.
    Language English
    Publishing date 2022-06-10
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2042-8898
    ISSN 2042-8898
    DOI 10.1098/rsfs.2021.0075
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  9. Article ; Online: Understanding virtual patients efficiently and rigorously by combining machine learning with dynamical modelling.

    Zhang, Tongli / Tyson, John J

    Journal of pharmacokinetics and pharmacodynamics

    2022  Volume 49, Issue 1, Page(s) 117–131

    Abstract: Individual biological organisms are characterized by daunting heterogeneity, which precludes describing or understanding populations of 'patients' with a single mathematical model. Recently, the field of quantitative systems pharmacology (QSP) has ... ...

    Abstract Individual biological organisms are characterized by daunting heterogeneity, which precludes describing or understanding populations of 'patients' with a single mathematical model. Recently, the field of quantitative systems pharmacology (QSP) has adopted the notion of virtual patients (VPs) to cope with this challenge. A typical population of VPs represents the behavior of a heterogeneous patient population with a distribution of parameter values over a mathematical model of fixed structure. Though this notion of VPs is a powerful tool to describe patients' heterogeneity, the analysis and understanding of these VPs present new challenges to systems pharmacologists. Here, using a model of the hypothalamic-pituitary-adrenal axis, we show that an integrated pipeline that combines machine learning (ML) and bifurcation analysis can be used to effectively and efficiently analyse the behaviors observed in populations of VPs. Compared with local sensitivity analyses, ML allows us to capture and analyse the contributions of simultaneous changes of multiple model parameters. Following up with bifurcation analysis, we are able to provide rigorous mechanistic insight regarding the influences of ML-identified parameters on the dynamical system's behaviors. In this work, we illustrate the utility of this pipeline and suggest that its wider adoption will facilitate the use of VPs in the practice of systems pharmacology.
    MeSH term(s) Humans ; Hypothalamo-Hypophyseal System ; Machine Learning ; Models, Theoretical ; Pituitary-Adrenal System
    Language English
    Publishing date 2022-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041601-5
    ISSN 1573-8744 ; 1567-567X
    ISSN (online) 1573-8744
    ISSN 1567-567X
    DOI 10.1007/s10928-021-09798-1
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  10. Article: Deficiency of the paternally-expressed imprinted

    Tyson, Hannah R / Harrison, David J / Higgs, Mathew J / Isles, Anthony R / John, Rosalind M

    Frontiers in neuroscience

    2024  Volume 18, Page(s) 1374781

    Abstract: Introduction: Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that ... ...

    Abstract Introduction: Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for
    Methods: WT female mice were mated with WT, heterozygous
    Results: We reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male
    Discussion: We have experimentally demonstrated that
    Language English
    Publishing date 2024-03-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2024.1374781
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