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Sivery2016 - A mammalian heat shock response model

ABSTRACT: Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics laws, is kept with a low dimensionality without altering the biological interpretation of the model dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of the network. Moreover, by a steady states analysis of the network, three different temperature stress regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes are consequences of the titration mechanism. The simplicity of the present model is of interest in order to study detailed modelling of cross regulation between the HSR and other major genetic networks like the cell cycle or the circadian clock. Sivéry, A., Courtade, E., Thommen, Q. (2016). A minimal titration model of the mammalian dynamical heat shock response. Physical biology, 13(6), 066008.

SUBMITTER: Quentin Thommen

PROVIDER: MODEL2201210001 | BioModels | 2022-01-25

REPOSITORIES: BioModels

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A minimal titration model of the mammalian dynamical heat shock response.

Sivéry Aude A Courtade Emmanuel E Thommen Quentin Q

Physical biology 20161207 6

Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene reg ...[more]

PMID: 27926536

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Project description:Proctor2005 - Actions of chaperones and their role in ageing This model is described in the article: Modelling the actions of chaperones and their role in ageing. Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TB. Mech. Ageing Dev. 2005 Jan; 126(1): 119-131 Abstract: Many molecular chaperones are also known as heat shock proteins because they are synthesised in increased amounts after brief exposure of cells to elevated temperatures. They have many cellular functions and are involved in the folding of nascent proteins, the re-folding of denatured proteins, the prevention of protein aggregation, and assisting the targeting of proteins for degradation by the proteasome and lysosomes. They also have a role in apoptosis and are involved in modulating signals for immune and inflammatory responses. Stress-induced transcription of heat shock proteins requires the activation of heat shock factor (HSF). Under normal conditions, HSF is bound to heat shock proteins resulting in feedback repression. During stress, cellular proteins undergo denaturation and sequester heat shock proteins bound to HSF, which is then able to become transcriptionally active. The induction of heat shock proteins is impaired with age and there is also a decline in chaperone function. Aberrant/damaged proteins accumulate with age and are implicated in several important age-related conditions (e.g. Alzheimer's disease, Parkinson's disease, and cataract). Therefore, the balance between damaged proteins and available free chaperones may be greatly disturbed during ageing. We have developed a mathematical model to describe the heat shock system. The aim of the model is two-fold: to explore the heat shock system and its implications in ageing; and to demonstrate how to build a model of a biological system using our simulation system (biology of ageing e-science integration and simulation (BASIS)). This model is hosted on BioModels Database and identified by: BIOMD0000000091. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:A study evaluating the effect of stress resistance selection of Drosophila melanogaster. Abstract Here, we report a detailed analysis of changes in gene expression in Drosophila melanogaster selected for multiple eological relevant environmental stress resistance traits. We analyzed females from three biological replicates from seven selection regimes and one control regime using whole genome gene expression arrays. Replicated selection lines were selected for resistance to acute heat survival, high temperature knock down, constant 30°C during development, cold shock survival, desiccation and starvation, respectively. Additionally, a set of replicated lines was selected for increased longevity. When compared to gene expression profiles of control lines, we were able to detect consistent selection responses at the transcript level in each specific selection regime and also found a group of differentially expressed genes that were generally changed among all selected lines. Replicated selection lines clustered together, i.e. showed similar changes in gene expression (compared to controls) and thus showed that 10 generations of artificial selection gives a clear signal among gene expression profiles. The changes in gene expression in lines selected for increased longevity, desiccation and starvation resistance, respectively, showed high similarities. Cold resistance selected lines showed little differentiation from controls. Different methods of heat selection (heat survival, heat knock down and constant 30°C) showed little similarity verifying that different mechanism are involved in high temperature adaptation. The direction of change in gene expression in the selected lines showed a consistent pattern for each selection regime. For most selection regimes and in the comparison of all selected lines and controls exclusively up- or down regulation of gene expression among significant differentially expressed genes was found. The different responses to selection expressed in individual selection regimes and among all selected lines indicate that we have identified genes involved in stress specific and general stress response mechanisms. Keywords: control versus selected

Dataset Information

Sivery2016 - A mammalian heat shock response model

Publications

A minimal titration model of the mammalian dynamical heat shock response.

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