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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
Bridge, L., Chen, S., & Jones, B. (2024). Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells and neurons. Cellular Signalling, 119, Article 111153. https://doi.org/10.1016/j.cellsig.2024.111153

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.

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.