ArticleBulletin of mathematical biology2014
The role of dimerisation and nuclear transport in the Hes1 gene regulatory network.
Article in Bulletin of mathematical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Modelling Population-Level Hes1 Dynamics: Insights from a Multi-framework Approach.Bulletin of mathematical biology · 2025Article
- RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1.EMBO reports · 2022Article
- A multiscale compartment-based model of stochastic gene regulatory networks using hitting-time analysis.The Journal of chemical physics · 2021Article
- Hierarchical algorithm for the reaction-diffusion master equation.The Journal of chemical physics · 2020Article
- Smart computational exploration of stochastic gene regulatory network models using human-in-the-loop semi-supervised learning.Bioinformatics (Oxford, England) · 2019Article
- Oscillations in well-mixed, deterministic feedback systems: Beyond ring oscillators.Journal of theoretical biology · 2019Article
- Revisiting the Reduction of Stochastic Models of Genetic Feedback Loops with Fast Promoter Switching.Biophysical journal · 2019Article
- A 3D Multiscale Model to Explore the Role of EGFR Overexpression in Tumourigenesis.Bulletin of mathematical biology · 2019Article
- Mesoscopic-microscopic spatial stochastic simulation with automatic system partitioning.The Journal of chemical physics · 2017Article
- Reaction rates for reaction-diffusion kinetics on unstructured meshes.The Journal of chemical physics · 2017Article
- The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt.PLoS computational biology · 2017Article
- MOLNs: A CLOUD PLATFORM FOR INTERACTIVE, REPRODUCIBLE, AND SCALABLE SPATIAL STOCHASTIC COMPUTATIONAL EXPERIMENTS IN SYSTEMS BIOLOGY USING PyURDME.SIAM journal on scientific computing : a publication of the Society for Industrial and Applied Mathematics · 2016Article
- MESOSCOPIC MODELING OF STOCHASTIC REACTION-DIFFUSION KINETICS IN THE SUBDIFFUSIVE REGIME.Multiscale modeling & simulation : a SIAM interdisciplinary journal · 2016Article
- Reaction rates for a generalized reaction-diffusion master equation.Physical review. E · 2016Article
- Mean field analysis of a spatial stochastic model of a gene regulatory network.Journal of mathematical biology · 2015Article
- Reaction rates for mesoscopic reaction-diffusion kinetics.Physical review. E, Statistical, nonlinear, and soft matter physics · 2015Article
- Local error estimates for adaptive simulation of the Reaction-Diffusion Master Equation via operator splitting.Journal of computational physics · 2014Article
- Editorial: special issue on stochastic modelling of reaction-diffusion processes in biology.Bulletin of mathematical biology · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hes1 is a member of the family of basic helix-loop-helix transcription factors and the Hes1 gene regulatory network (GRN) may be described as the canonical example of transcriptional control in eukaryotic cells, since it involves only the Hes1 protein and its own mRNA. Recently, the Hes1 protein has been established as an excellent target for an anti-cancer drug treatment, with the design of a small molecule Hes1 dimerisation inhibitor representing a promising if challenging approach to therapy. In this paper, we extend a previous spatial stochastic model of the Hes1 GRN to include nuclear transport and dimerisation of Hes1 monomers. Initially, we assume that dimerisation occurs only in the cytoplasm, with only dimers being imported into the nucleus. Stochastic simulations of this novel model using the URDME software show that oscillatory dynamics in agreement with experimental studies are retained. Furthermore, we find that our model is robust to changes in the nuclear transport and dimerisation parameters. However, since the precise dynamics of the nuclear import of Hes1 and the localisation of the dimerisation reaction are not known, we consider a second modelling scenario in which we allow for both Hes1 monomers and dimers to be imported into the nucleus, and we allow dimerisation of Hes1 to occur everywhere in the cell. Once again, computational solutions of this second model produce oscillatory dynamics in agreement with experimental studies. We also explore sensitivity of the numerical solutions to nuclear transport and dimerisation parameters. Finally, we compare and contrast the two different modelling scenarios using numerical experiments that simulate dimer disruption, and suggest a biological experiment that could distinguish which model more faithfully captures the Hes1 GRN.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.