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Séminaire INRIabcd

On the dynamical role of stochastic fluctuations in cell differentiation

by Mr. Andrea Rocco (University of Surrey)

mardi 2 mai 2017 de au (Europe/Paris)
at INRIA- antenne Lyon- La Doua, Bâtiment CEI-2 (tram: T1-IUT FEYSSINE) ( 432 (4ème étage) )
INRIA- antenne Lyon- La Doua, Bâtiment CEI-2 (tram: T1-IUT FEYSSINE)
A major problem in developmental biology is to understand how different cell types emerge from the one genome of multipotent precursor cells. In 1957, C.H. Waddington introduced the so-called epigenetic landscape to represent the complex regulatory dynamics driving the differentiation process. The differentiating cell explores the landscape, and by encountering successive decision points, proceeds towards its eventual fate. Changes in the morphology of the landscape that favour one cell type over others are a reflection of dynamical changes occurring in the underlying cellular gene regulatory network. Despite much progress in the field, what drives these changes still remains a largely unanswered question.

In this talk I will review some of the possible mathematical scenarios that have been proposed to describe decision points in Waddington’s landscape. Within the context of Dynamical Systems Theory these decision points are seen as mathematical bifurcations, which can be further modified and enriched when stochastic fluctuations (so-called noise) are considered. Noise is ubiquitous in molecular biology, and occurs in many aspects of gene regulation and other cellular activities, accounting for much if not all of the variability that we see in biological systems. I will present some recent results obtained in my group in the case of simple stochastic gene systems exhibiting time scale separation between fast and slow variables. I will discuss conditions involving the time-scale of the system and the correlation time of the noise, which lead to the emergence of non-trivial reduced dynamics and new types of noise-induced bifurcations. 

Not only our theoretical findings suggest a fundamental role played by biological noise in development, but they are also relevant in the broader context of understanding the stochastic dynamics of gene regulatory circuits. Our predictions, if experimentally confirmed, will have implications far beyond the fundamental biology of the cell differentiation process, with medical implications in congenital diseases and cancer. 
Organisé par Léon Matar Tine, Laurent Pujo-Menjouet, Guillaume Beslon