A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi

Tao You, Piers Ingram, Mette D Jacobsen, Emily Cook, Andrew McDonagh, Thomas Thorne, Megan D Lenardon, Alessandro P S de Moura, M Carmen Romano, Marco Thiel, Michael Stumpf, Neil A R Gow, Ken Haynes, Celso Grebogi, Jaroslav Stark, Alistair J P Brown

Research output: Contribution to journalArticle

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Abstract

Background
Saccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation. Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans.

Results
We combined modeling and experimental approaches to study osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple ordinary differential equation (ODE) model that highlights the integral control that Hog1 exerts over glycerol biosynthesis in these species. If integral control arises from a separation of time scales (i.e. rapid HOG activation of glycerol production capacity which decays slowly under hyperosmotic conditions), then the model predicts that glycerol production rates elevate upon adaptation to a first stress and this makes the cell adapts faster to a second hyperosmotic stress. It appears as if the cell is able to remember the stress history that is longer than the timescale of signal transduction. This is termed the long-term stress memory. Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes glycerol efflux during adaptation to hyperosmolarity. Also, transient activation of intermediate kinases in the HOG pathway results in a short-term memory in the signaling pathway. This determines the amplitude of Hog1 phosphorylation under a periodic sequence of stress and non-stressed intervals. Our model suggests that the long-term memory also affects the way a cell responds to periodic stress conditions. Hence, during osmohomeostasis, short-term memory is dependent upon long-term memory. This is relevant in the context of fungal responses to dynamic and changing environments.

Conclusions
Our experiments and modeling have provided an example of identifying integral control that arises from time-scale separation in different processes, which is an important functional module in various contexts.
Original languageEnglish
Article number258
Number of pages16
JournalBMC Research Notes
Volume5
DOIs
Publication statusPublished - 25 May 2012

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Systems Biology
Long-Term Memory
Osmotic Pressure
Fungi
Short-Term Memory
Glycerol
Data storage equipment
Candida albicans
Saccharomyces cerevisiae
Chemical activation
Osmoregulation
Signal transduction
Phosphorylation
Candida
Biosynthesis
Heat-Shock Proteins
Gene expression
Ordinary differential equations
Protein Kinases
Signal Transduction

Cite this

A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi. / You, Tao; Ingram, Piers; Jacobsen, Mette D; Cook, Emily; McDonagh, Andrew; Thorne, Thomas; Lenardon, Megan D; de Moura, Alessandro P S; Romano, M Carmen; Thiel, Marco; Stumpf, Michael; Gow, Neil A R; Haynes, Ken; Grebogi, Celso; Stark, Jaroslav; Brown, Alistair J P.

In: BMC Research Notes, Vol. 5, 258, 25.05.2012.

Research output: Contribution to journalArticle

You, Tao ; Ingram, Piers ; Jacobsen, Mette D ; Cook, Emily ; McDonagh, Andrew ; Thorne, Thomas ; Lenardon, Megan D ; de Moura, Alessandro P S ; Romano, M Carmen ; Thiel, Marco ; Stumpf, Michael ; Gow, Neil A R ; Haynes, Ken ; Grebogi, Celso ; Stark, Jaroslav ; Brown, Alistair J P. / A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi. In: BMC Research Notes. 2012 ; Vol. 5.
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abstract = "BackgroundSaccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation. Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans.ResultsWe combined modeling and experimental approaches to study osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple ordinary differential equation (ODE) model that highlights the integral control that Hog1 exerts over glycerol biosynthesis in these species. If integral control arises from a separation of time scales (i.e. rapid HOG activation of glycerol production capacity which decays slowly under hyperosmotic conditions), then the model predicts that glycerol production rates elevate upon adaptation to a first stress and this makes the cell adapts faster to a second hyperosmotic stress. It appears as if the cell is able to remember the stress history that is longer than the timescale of signal transduction. This is termed the long-term stress memory. Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes glycerol efflux during adaptation to hyperosmolarity. Also, transient activation of intermediate kinases in the HOG pathway results in a short-term memory in the signaling pathway. This determines the amplitude of Hog1 phosphorylation under a periodic sequence of stress and non-stressed intervals. Our model suggests that the long-term memory also affects the way a cell responds to periodic stress conditions. Hence, during osmohomeostasis, short-term memory is dependent upon long-term memory. This is relevant in the context of fungal responses to dynamic and changing environments.ConclusionsOur experiments and modeling have provided an example of identifying integral control that arises from time-scale separation in different processes, which is an important functional module in various contexts.",
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T1 - A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi

AU - You, Tao

AU - Ingram, Piers

AU - Jacobsen, Mette D

AU - Cook, Emily

AU - McDonagh, Andrew

AU - Thorne, Thomas

AU - Lenardon, Megan D

AU - de Moura, Alessandro P S

AU - Romano, M Carmen

AU - Thiel, Marco

AU - Stumpf, Michael

AU - Gow, Neil A R

AU - Haynes, Ken

AU - Grebogi, Celso

AU - Stark, Jaroslav

AU - Brown, Alistair J P

PY - 2012/5/25

Y1 - 2012/5/25

N2 - BackgroundSaccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation. Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans.ResultsWe combined modeling and experimental approaches to study osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple ordinary differential equation (ODE) model that highlights the integral control that Hog1 exerts over glycerol biosynthesis in these species. If integral control arises from a separation of time scales (i.e. rapid HOG activation of glycerol production capacity which decays slowly under hyperosmotic conditions), then the model predicts that glycerol production rates elevate upon adaptation to a first stress and this makes the cell adapts faster to a second hyperosmotic stress. It appears as if the cell is able to remember the stress history that is longer than the timescale of signal transduction. This is termed the long-term stress memory. Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes glycerol efflux during adaptation to hyperosmolarity. Also, transient activation of intermediate kinases in the HOG pathway results in a short-term memory in the signaling pathway. This determines the amplitude of Hog1 phosphorylation under a periodic sequence of stress and non-stressed intervals. Our model suggests that the long-term memory also affects the way a cell responds to periodic stress conditions. Hence, during osmohomeostasis, short-term memory is dependent upon long-term memory. This is relevant in the context of fungal responses to dynamic and changing environments.ConclusionsOur experiments and modeling have provided an example of identifying integral control that arises from time-scale separation in different processes, which is an important functional module in various contexts.

AB - BackgroundSaccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation. Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans.ResultsWe combined modeling and experimental approaches to study osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple ordinary differential equation (ODE) model that highlights the integral control that Hog1 exerts over glycerol biosynthesis in these species. If integral control arises from a separation of time scales (i.e. rapid HOG activation of glycerol production capacity which decays slowly under hyperosmotic conditions), then the model predicts that glycerol production rates elevate upon adaptation to a first stress and this makes the cell adapts faster to a second hyperosmotic stress. It appears as if the cell is able to remember the stress history that is longer than the timescale of signal transduction. This is termed the long-term stress memory. Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes glycerol efflux during adaptation to hyperosmolarity. Also, transient activation of intermediate kinases in the HOG pathway results in a short-term memory in the signaling pathway. This determines the amplitude of Hog1 phosphorylation under a periodic sequence of stress and non-stressed intervals. Our model suggests that the long-term memory also affects the way a cell responds to periodic stress conditions. Hence, during osmohomeostasis, short-term memory is dependent upon long-term memory. This is relevant in the context of fungal responses to dynamic and changing environments.ConclusionsOur experiments and modeling have provided an example of identifying integral control that arises from time-scale separation in different processes, which is an important functional module in various contexts.

U2 - 10.1186/1756-0500-5-258

DO - 10.1186/1756-0500-5-258

M3 - Article

VL - 5

JO - BMC Research Notes

JF - BMC Research Notes

SN - 1756-0500

M1 - 258

ER -