Model-Driven Experimentation Perspective Paper Accepted

Posted on 19 December 2016

A new perspective article on the use of model-driven experimentation in exploring the formation, function, and therapeutic resolution of tertiary lymphoid tissues has been accepted for publication by Frontiers in Immunology

The publication, by lab members James Butler, Jason Cosgrove, Kieran Alden, Jon Timmis, and Mark Coles, is now available from the Frontiers in Immunology web site. In the perspective, we make the case for applying model-driven experimentation using two case studies which combined simulations with experiments to identify mechanisms driving lymphoid tissue formation and function, and then discuss potential applications of this experimental paradigm to identify novel therapeutic targets for TLT pathology.

Full Abstract:

The molecular and cellular processes driving the formation of secondary lymphoid tissues have been extensively studied using a combination of mouse knockouts, lineage specific reporter mice, gene expression analysis, immunohistochemistry and flow cytometry. However, the mechanisms driving the formation and function of tertiary lymphoid tissue (TLT) experimental techniques have proven to be more enigmatic and controversial due to differences between experimental models and human disease pathology. Systems-based approaches including data-driven biological network analysis (Gene Interaction Network, Metabolic Pathway Network, Cell-Cell signalling & cascade networks) and mechanistic modelling afford a novel perspective from which to understand TLT formation and identify mechanisms that may lead to the resolution of tissue pathology. In this perspective, we make the case for applying model-driven experimentation using two case studies which combined simulations with experiments to identify mechanisms driving lymphoid tissue formation and function, and then discuss potential applications of this experimental paradigm to identify novel therapeutic targets for TLT pathology.