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Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory (2023)
Journal Article
White, C., Rottschäfer, V., & Bridge, L. (in press). Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory. Journal of Pharmacokinetics and Pharmacodynamics, https://doi.org/10.1007/s10928-023-09870-y

Mathematical modelling has become a key tool in pharmacological analysis, towards understanding dynamics of cell signalling and quantifying ligand-receptor interactions. Ordinary differential equation (ODE) models in receptor theory may be used to pa... Read More about Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory.

NanoBiT‐ and NanoBiT/BRET‐based assays allow the analysis of binding kinetics of Wnt‐3a to endogenous Frizzled 7 in a colorectal cancer model (2023)
Journal Article
Grätz, L., Sajkowska-Kozielewicz, J. J., Wesslowski, J., Kinsolving, J., Bridge, L. J., Petzold, K., …Kozielewicz, P. (in press). NanoBiT‐ and NanoBiT/BRET‐based assays allow the analysis of binding kinetics of Wnt‐3a to endogenous Frizzled 7 in a colorectal cancer model. British Journal of Pharmacology, https://doi.org/10.1111/bph.16090

Background and Purpose: Wnt binding to Frizzleds (FZD) is a crucial step that leads to the initiation of signalling cascades governing multiple processes during embryonic development, stem cell regulation and adult tissue homeostasis. Recent efforts... Read More about NanoBiT‐ and NanoBiT/BRET‐based assays allow the analysis of binding kinetics of Wnt‐3a to endogenous Frizzled 7 in a colorectal cancer model.

Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins (2022)
Journal Article
Maqsood, Z., Clark, J. C., Martin, E. M., Cheung, Y. F. H., Morán, L. A., Watson, S. E. T., …Watson, S. P. (2022). Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins. PLoS Computational Biology, 18(11), Article e1010708. https://doi.org/10.1371/journal.pcbi.1010708

The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) dom... Read More about Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins.

Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis (2022)
Journal Article
White, C., Rottschäfer, V., & Bridge, L. (2022). Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis. Journal of Theoretical Biology, 538, 110996. https://doi.org/10.1016/j.jtbi.2021.110996

The vascular endothelial growth factor (VEGF) receptor (VEGFR) system plays a role in cancer and many other diseases. It is widely accepted that VEGFR receptors dimerise in response to VEGF binding. However, analysis of these mechanisms and their imp... Read More about Insights into the dynamics of ligand-induced dimerisation via mathematical modelling and analysis.

Exact solutions and equi-dosing regimen regions for multi-dose pharmacokinetics models with transit compartments (2020)
Journal Article
Hof, F., & Bridge, L. J. (2021). Exact solutions and equi-dosing regimen regions for multi-dose pharmacokinetics models with transit compartments. Journal of Pharmacokinetics and Pharmacodynamics, 48, 99-131. https://doi.org/10.1007/s10928-020-09719-8

Compartmental models which yield linear ordinary differential equations (ODEs) provide common tools for pharmacokinetics (PK) analysis, with exact solutions for drug levels or concentrations readily obtainable for low-dimensional compartment models.... Read More about Exact solutions and equi-dosing regimen regions for multi-dose pharmacokinetics models with transit compartments.

Analyzing kinetic signaling data for G-protein-coupled receptors (2020)
Journal Article
Hoare, S. R. J., Tewson, P. H., Quinn, A. M., Hughes, T. E., & Bridge, L. J. (2020). Analyzing kinetic signaling data for G-protein-coupled receptors. Scientific Reports, 10, Article 12263. https://doi.org/10.1038/s41598-020-67844-3

In classical pharmacology, bioassay data are fit to general equations (e.g. the dose response equation) to determine empirical drug parameters (e.g. EC50 and Emax), which are then used to calculate chemical parameters such as affinity and efficacy. H... Read More about Analyzing kinetic signaling data for G-protein-coupled receptors.

A two-state model for the kinetics of competitive radioligand binding (2018)
Journal Article
Guo, D., Peletier, L. A., Bridge, L., Keur, W., de Vries, H., Zweemer, A., …Ijzerman, A. P. (2018). A two-state model for the kinetics of competitive radioligand binding. British Journal of Pharmacology, 175(10), 1719-1730. https://doi.org/10.1111/bph.14184

© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. Background and Purpose: Ligand–receptor binding kinetics is receiving increasing attention in the drug research co... Read More about A two-state model for the kinetics of competitive radioligand binding.

Ligand binding dynamics for pre-dimerised G protein-coupled receptor homodimers: Linear models and analytical solutions (2018)
Journal Article
White, C., & Bridge, L. (2019). Ligand binding dynamics for pre-dimerised G protein-coupled receptor homodimers: Linear models and analytical solutions. Bulletin of Mathematical Biology, 81(9), 3542-3574. https://doi.org/10.1007/s11538-017-0387-x

Evidence suggests that many G protein-coupled receptors (GPCRs) are bound together forming dimers. The implications of dimerisation for cellular signalling outcomes, and ultimately drug discovery and therapeutics, remain unclear. Consideration of lig... Read More about Ligand binding dynamics for pre-dimerised G protein-coupled receptor homodimers: Linear models and analytical solutions.

Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor (2018)
Journal Article
Bridge, L., Mead, J., Frattini, E., Winfield, I., & Ladds, G. (2018). Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor. Journal of Theoretical Biology, 442, 44-65. https://doi.org/10.1016/j.jtbi.2018.01.010

© 2018 The Authors Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been... Read More about Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.

Dynamic NF-κb and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation (2016)
Journal Article
Harper, C. V., Adamson, A. D., White, M. R., Jones, N. A., Jackson, D. A., Ankers, J. M., …White, M. R. (2016). Dynamic NF-κb and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation. eLife, 5(MAY2016), https://doi.org/10.7554/eLife.10473

© Ankers et al. Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are... Read More about Dynamic NF-κb and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation.

A method of ‘speed coefficients’ for biochemical model reduction applied to the NF-κB system (2014)
Journal Article
West, S., Bridge, L. J., White, M. R. H., Paszek, P., & Biktashev, V. N. (2015). A method of ‘speed coefficients’ for biochemical model reduction applied to the NF-κB system. Journal of Mathematical Biology, 70(3), 591-620. https://doi.org/10.1007/s00285-014-0775-x

© 2014, The Author(s). The relationship between components of biochemical network and the resulting dynamics of the overall system is a key focus of computational biology. However, as these networks and resulting mathematical models are inherently co... Read More about A method of ‘speed coefficients’ for biochemical model reduction applied to the NF-κB system.

Impact of plant shoot architecture on leaf cooling: A coupled heat and mass transfer model (2013)
Journal Article
Bridge, L. J., Bridge, L., Franklin, K. A., & Homer, M. E. (2013). Impact of plant shoot architecture on leaf cooling: A coupled heat and mass transfer model. Interface, 10(85), 20130326. https://doi.org/10.1098/rsif.2013.0326

Plants display a range of striking architectural adaptations when grown at elevated temperatures. In the model plant Arabidopsis thaliana, these include elongation of petioles, and increased petiole and leaf angles from the soil surface. The potentia... Read More about Impact of plant shoot architecture on leaf cooling: A coupled heat and mass transfer model.

Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets (2012)
Journal Article
Bridge, L., Mirams, G. R., Kieffer, M. L., King, J. R., & Kepinski, S. (2012). Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets. Mathematical Biosciences, 235(1), 32-44. https://doi.org/10.1016/j.mbs.2011.10.005

New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Ke... Read More about Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets.

Allosteric interactions across native adenosine-A 3 receptor homodimers: Quantification using single-cell ligand-binding kinetics (2011)
Journal Article
May, L. T., Bridge, L., Stoddart, L. A., Briddon, S. J., & Hill, S. J. (2011). Allosteric interactions across native adenosine-A 3 receptor homodimers: Quantification using single-cell ligand-binding kinetics. FASEB Journal, 25(10), 3465-3476. https://doi.org/10.1096/fj.11-186296

A growing awareness indicates that many G-protein-coupled receptors (GPCRs) exist as homodimers, but the extent of the cooperativity across the dimer interface has been largely unexplored. Here, measurement of the dissociation kinetics of a fluoresce... Read More about Allosteric interactions across native adenosine-A 3 receptor homodimers: Quantification using single-cell ligand-binding kinetics.

Modelling of the activation of G-protein coupled receptors: Drug free constitutive receptor activity (2010)
Journal Article
Woodroffe, P. J., Bridge, L., King, J. R., Chen, C. Y., & Hill, S. J. (2010). Modelling of the activation of G-protein coupled receptors: Drug free constitutive receptor activity. Journal of Mathematical Biology, 60(3), 313-346. https://doi.org/10.1007/s00285-009-0268-5

G-protein coupled receptors (GPCRs) form a crucial component of approximately 80% of hormone pathways. In this paper, the most popular mechanism for activation of GPCRs-the shuttling mechanism-is modelled mathematically. An asymptotic analysis of thi... Read More about Modelling of the activation of G-protein coupled receptors: Drug free constitutive receptor activity.

Mathematical modelling of signalling in a two-ligand G-protein coupled receptor system: Agonist-antagonist competition (2010)
Journal Article
Bridge, L., King, J. R., Hill, S. J., & Owen, M. R. (2010). Mathematical modelling of signalling in a two-ligand G-protein coupled receptor system: Agonist-antagonist competition. Mathematical Biosciences, 223(2), 115-132. https://doi.org/10.1016/j.mbs.2009.11.005

A new mathematical model of cell signalling for a two-ligand G-protein coupled receptor (GPCR) system is presented. This model extends the single-ligand cubic ternary complex to account for the possibility of an agonist and an antagonist competing fo... Read More about Mathematical modelling of signalling in a two-ligand G-protein coupled receptor system: Agonist-antagonist competition.

Modelling the activation of G-protein coupled receptors by a single drug (2009)
Journal Article
Woodroffe, P. J., Bridge, L., King, J. R., & Hill, S. J. (2009). Modelling the activation of G-protein coupled receptors by a single drug. Mathematical Biosciences, 219(1), 32-55. https://doi.org/10.1016/j.mbs.2009.02.003

In this paper, the most popular proposed mechanism for activation of G-protein coupled receptors (GPCRs) - the shuttling mechanism - is modelled mathematically. An asymptotic analysis of this model clarifies the dynamics of the system in the presence... Read More about Modelling the activation of G-protein coupled receptors by a single drug.

A mixture formulation for numerical capturing of a two-phase/vapour interface in a porous medium (2007)
Journal Article
Bridge, L., & Wetton, B. R. (2007). A mixture formulation for numerical capturing of a two-phase/vapour interface in a porous medium. Journal of Computational Physics, 225(2), 2043-2068. https://doi.org/10.1016/j.jcp.2007.03.011

A model problem for two-phase fluid flow and heat transfer with phase change in a porous medium is described. The model is based on a steam-water mixture in sand. Under certain conditions, a two-phase zone, in which liquid and vapour coexist, is sepa... Read More about A mixture formulation for numerical capturing of a two-phase/vapour interface in a porous medium.

The analysis of a two-phase zone with condensation in a porous medium (2003)
Journal Article
Bridge, L., Bradean, R., Ward, M. J., & Wetton, B. R. (2003). The analysis of a two-phase zone with condensation in a porous medium. Journal of Engineering Mathematics, 45(3-4), 247-268. https://doi.org/10.1023/A%3A1022690802938

The one-dimensional steady-state heat and mass transfer in a two-phase zone of a water-saturated porous medium is studied. The system consists of a sand-water-vapour mixture in a tube that is heated from above and cooled from below. Under certain con... Read More about The analysis of a two-phase zone with condensation in a porous medium.