The Stressed Cell as a Physical Aging Problem

This project aims to develop a statistical physics framework to analyze cellular responses to acute stress, revealing network dynamics and informing synthetic biology and treatment strategies.

Subsidie
€ 2.497.500
2022

Projectdetails

Introduction

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.

Premise

My premise is that when a cell encounters an acute, but non-lethal, stress, its perturbed state can be modeled 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.

Goal

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.

Methodology

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.
  3. New biophysical measurements of the transition from the regulated to the disrupted cellular network.

Expected Outcomes

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.

Implications

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.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 2.497.500
Totale projectbegroting€ 2.497.500

Tijdlijn

Startdatum1-7-2022
Einddatum30-6-2027
Subsidiejaar2022

Partners & Locaties

Projectpartners

  • THE HEBREW UNIVERSITY OF JERUSALEMpenvoerder

Land(en)

Israel

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