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The Stressed Cell as a Physical Aging Problem

Descripción del proyecto

La física estadísticas proporciona información novedosa sobre el estado de células estresadas

Las células constan de microambientes muy complejos, con múltiples interacciones que tienen lugar a la vez entre todos sus componentes. Este hecho dificulta el uso de métodos estadísticos para evaluar el comportamiento celular. El objetivo del proyecto StatCell, financiado con fondos europeos, es superar este reto mediante la elaboración de un marco experimental y teórico para describir la física estadística de las células sometidas a estrés agudo. El equipo de StatCell combinará técnicas de biología celular punteras en pos de identificar las condiciones de la red celular que se pueden predecir de forma cuantitativa con un marco de física estadística. Su trabajo proporcionará información relevante sobre los mecanismos celulares relacionados con el envejecimiento y las enfermedades.

Objetivo

Statistical physics successfully accounts for phenomena involving a large number of components using a probabilistic approach with predictions for collective properties of the system. While biological cells contain a very large number of interacting components, (proteins, RNA molecules, metabolites, etc.), the cellular network is understood as a particular, highly specific, choice of interactions shaped by evolution, and therefore not amenable to a statistical physics description. My premise is that when a cell encounters an acute, but non-lethal, stress, its perturbed state can be modelled as random network dynamics, rather than as a regulated response. Strong perturbations may therefore reveal the dynamics of the underlying network that are amenable to a statistical physics description. Based on the striking similarity between our data on stressed bacteria and physical aging in disordered systems, my goal is to develop an experimental and theoretical framework for the statistical physics description of cells exposed to strong perturbations. We will critically probe the predictions of the statistical model using a multidisciplinary approach combining three frontline methodologies: (1) dynamics of single bacteria under acute stress in microfluidic devices and single cell transcriptomics; (2) theoretical framework and simulations for cellular networks under acute stress; and (3) new biophysical measurements of the transition from the regulated to the disrupted cellular network. This approach should provide a paradigm shift in the analysis of cells under stress, differentiating between conditions described by the regulation of gene networks from those that can be quantitatively predicted by a statistical physics framework. The new knowledge should lead to innovative ways of controlling the cellular network under strong perturbations, with implications ranging from new methodologies for synthetic biology to new avenues for treating bacterial infections and cancer.

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Coordinador

THE HEBREW UNIVERSITY OF JERUSALEM
Aportación neta de la UEn
€ 2 497 500,00
Dirección
Edmond j safra campus givat ram
91904 Jerusalem
Israel

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Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Otras fuentes de financiación
€ 0,00