Cell decision making in complex signalling environments

1 October 2021

Jonathan Chubb
MRC Laboratory for Molecular Cell Biology
University College, London

zoom recording

Abstract

Despite the intense activity in the field of developmental biology for many decades, our understanding of how cells make decisions about their fate is decidedly limited. Models tend to fall into two categories – instructive or permissive. Instructive models emphasise the external or inherited trigger, giving the cell no choice. Permissive models view the cell as waiting for some event that triggers a decision already made, often incorporating a central "noise plus feedback" element. These models can be useful in the limited number of apparently simple contexts in which cell fates appear to be determined by a limited number of components, yet in most systems, which are neither wholly instructive nor permissive, and often depend on a highly complex set of interactions between the cell and its environment, these opposing models lack utility.

Although progress has been made by studying specific molecules, these approaches do not reveal the complexity of how the niche interacts with the cell, and we are far from having a fully parameterised catalogue of all the salient molecular interactions occurring within the cell. The primary problem we face is to determine the appropriate level of organisation at which we focus our efforts, and to measure all the implicated agents in the decision-making process (such signals, cells, transcription factors etc. ) within a meaningful physiological dynamic range. I will tentatively outline what we think may be possible.

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