Speaker
Description
Radial dysplasia (RD) is a musculoskeletal disorder in which the anatomical structure of the forelimb is fundamentally altered - in extreme cases the radius bone is missing, along with a number of muscles. RD is a disorder of later development, that manifests through changes in the extracellular matrix (ECM) deposition behaviour of a population of fibroblast precursors. As muscle cells follow patterning cues in the ECM, this change in fibroblast behaviour and ECM organisation propagates in multiple complex ways to alterations in muscle cell alignment. In my project I am using predictive computational modelling to understand how these emergent changes at the tissue-level derive from collective cell interactions. To do this, I have acquired a rich dataset of collective cell motion timelapse data, designed a model of cellular collective motion incorporating fine-grained simulation of cell motion, and have implemented a novel analysis inspired by methods from information geometry and simulation-based inference to both fit this data and pursue global model reduction. Unexpectedly, I have found that greater collective organisation of cells due to nematic alignment and flocking behaviours can, when ECM feedback is allowed, derange the process of depositing globally organised ECM.
