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Theory of Living Matter Group

 

11th General Meeting

General information

In our 11th General Meeting, we will learn about how to combine theory and experiments to understand Developmental Dynamics: From Stem Cells to Organisms. Our speakers in this meeting will be Prof Olivier Pourquié from Harvard University and Prof Michael Stumpf from the Imperial College London.

After the talk there will be a drinks reception with snacks and plenty of time for informal discussions.

Registration:
No registration required.

Date:
Wednesday, 18th April 2018, 6pm

Venue:
Palmerston Room, Fisher Building
St John's College, Cambridge CB2 1TP

Directions: On arrival, please report to St John's College Porter's Lodge on St John's Street to enter the College and then head towards the Fisher Building. If you're not sure about the direction, please ask the porters or see the map: Detailed map of St John's College

Talks

“Deconstructing the Segmentation Clock oscillator in vitro”

Olivier Pourquié, Harvard University

The periodic segmentation of the vertebrate body axis into somites, and later vertebrae, relies on a genetic oscillator (the Segmentation Clock) driving the rhythmic activity of signaling pathways in the presomitic mesoderm (PSM). While the clock is often presented as a population of phase-entrained oscillators, whether its oscillations are an intrinsic property of individual cells or represent a population-level phenomenon is not known. Using tail bud explants from mouse embryos, we show that oscillations are a collective property of PSM cells which can be actively triggered in vitro by a dynamical quorum sensing signal. We demonstrate that inhibiting Yap signaling is sufficient to predictably switch isolated PSM cells from a quiescent to an oscillatory state in vitro, a behavior reminiscent of excitability in other systems. We have also engineered a human iPS line carrying a fluorescent reporter driven by the regulatory sequences of the HES7 cyclic gene. This line can be efficiently induced to differentiate to a PSM fate in vitro by activating Wnt and inhibiting BMP signaling. Human PSM-like cells exhibit regular oscillations with a 5 hour periodicity. Together, this work argues that the mammalian segmentation clock behaves as an excitable system, introducing a novel paradigm to study such dynamics in vertebrate morphogenesis. Furthermore, we identify and characterize the human Segmentation Clock, introducing a robust in vitro system to dissect the molecular clockwork underlying this oscillator.


“Transition State Theory of Stem Cell Differentiation”

Michael Stumpf, Imperial College London

Current emphasis in single cell analysis, especially in the context of the cell atlas projects, is on characterising the transcriptomic signatures of different cell states. This is clearly of great importance, as even the number of different cell types, e.g. in humans, is not known with any satisfying degree of certainty. There are enormous challenges in mapping these states, but this will still only provide a partial answer: importantly, the way in which cells differentiate, and the way in which gene expression changes over the course of differentiation will still be unknown. Here we use a dynamical systems perspective and ideas from non-equilibrium statistical mechanics to consider the nature of, and dynamics during the transition between different cell states, and to characterize the transition state. We find, for example, that such transitions will occur very quickly, and it will in practice be hard to "catch" a transitioning cell, e.g. in a single cell transcriptomic study. Throughout the talk I will try to highlight a few mathematical properties that are necessarily shared by developmental systems, and which can be useful for the analysis of developmental hypotheses and data.

Sponsors

This event is organised by the Theory of Living Matter Group and supported by the Wellcome Trust/Medical Research Council Stem Cell Institute and the Cambridge Philosophical Society.