WG/GLIMPRINT Seminars: Gall, Intestinal Crypts and Drug Induced Injury, March 20, 2025

Описание: Mathematical Modelling of Drug-induced Injury of the Intestinal Crypt
Louis Gall, PhD
Birmingham University

*Winner BioModels Model of the Year Competition 2024

The cells of the intestinal epithelium are produced within invaginations called crypts, whose constituent cells carefully balance proliferation and differentiation to maintain a functional intestinal epithelium. To investigate these dynamics, in homeostasis and under drug-induced perturbations, we built a pair of multi-scale mathematical models of cells interacting in the intestinal crypt that reproduces the observed dynamic self-organisation necessary for a healthy intestinal epithelium. The first model is a typical ODE-based approach, that models the dynamics of cell populations and feedback mechanisms between different cell types and locations. The second is an agent-based model (ABM) that simulates multiple signalling pathways and the cell cycle protein network within each cell. Each biological pathways in the ABM can be perturbed to simulate the effect of drugs or disease, using the model to simulate the propagation of the single-cell disruption to a tissue-scale injury. This framework provides a novel toolbox for exploring the mechanisms of intestinal homeostasis and their disruption in disease, that can adapt to different levels of data availability and granularity.

For more information see:
Homeostasis, injury, and recovery dynamics at multiple scales in a self-organizing mouse intestinal crypt, https://elifesciences.org/articles/85478

A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity, https://ascpt.onlinelibrary.wiley.com...

https://www.ebi.ac.uk/biomodels/compe...

*Contents
00:00 - Introduction
09:53 - Mathematical Modelling of Drug-induced Injury of the Intestinal Crypt
49:10 - Questions and Discussions

Moderator: James A. Glazier

For the slides in this video, visit: https://docs.google.com/presentation/...

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