Inferring causality in complex molecular pathways from live cell movies

EVENT : C3BI Seminars

Inferring causAlity in complex molecular pathways from live cell movies 

Main speaker : Gaudenz Danuser, from Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science Bioinformatics, Cell Biology UT Southwestern, Dallas, USA Date : 22-02-2018 at 02:00 pm Location : Retrovirus room – LWOFF (22) ,Institut Pasteur, Paris

One of the major limitations in the study of complex molecular pathways is adaptation of the system to experimental perturbation. With ‘complex’ we mean pathways with a significant level of functional redundancy between components and nonlinear interactions. In this scenario, perturbation of one component may lead to an observable phenotype. However, it is impossible to interpret the difference between phenotype and wildtype in terms of the function the targeted component fulfills in the unperturbed system – although this is the predominant approach cell and systems biologists take to dissect molecular functions. Over the past decade my lab has made efforts to circumvent this problem by exploiting the basal fluctuations of molecular activities observed in live cell movies to establish causal functional relations between pathway components. Inspired by the accomplishments of econometrics, where predictive models are built entirely from passive observation of financial fluctuation time series, we have developed a computational framework to determine nonlinear interdependencies between pathway components. This presentation will introduce some of the mathematical, computational, and experimental concepts based on which we can now accurately delineate the functional hierarchy between signaling and mechanical processes that control cellular morphogenesis, which is a prime example of a complex molecular process.

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