Outputs (21)

Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells and neurons (2024)
Journal Article

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) which plays important physiological roles in insulin release and promoting fullness. GLP-1R agonists initiate cellular responses by cyclic AMP (cAMP) pathway... Read More about Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells and neurons.

Classical structural identifiability methodology applied to low-dimensional dynamic systems in receptor theory (2023)
Journal Article

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

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

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

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

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

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

© 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

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

© 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

© 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

© 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

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

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

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

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

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.

Modeling and simulation of inverse agonism dynamics (2010)
Book Chapter

With the recent discovery and increased recognition of constitutive activity of G-protein coupled receptors (GPCRs) and inverse agonists have come a number of important questions. The signaling mechanisms underlying inverse agonist effects on constit... Read More about Modeling and simulation of inverse agonism dynamics.

Modelling the activation of G-protein coupled receptors by a single drug (2009)
Journal Article

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

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

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.