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

• Main Authors: You Tao, Ingram Piers, Jacobsen Mette D, Cook Emily, McDonagh Andrew, Thorne Thomas, Lenardon Megan D, de Moura Alessandro PS, Romano M, Thiel Marco, Stumpf Michael, Gow Neil AR, Haynes Ken, Grebogi Celso, Stark Jaroslav, Brown Alistair JP
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: BMC Research Notes
• Online Access: http://www.biomedcentral.com/1756-0500/5/258

<p><b>Abstract</b></p> <p><b>Background</b></p> <p><it>Saccharomyces cerevisiae</it> 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. <it>Candida albicans</it> also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in <it>C. albicans</it>.</p> <p><b>Results</b></p> <p>We combined modeling and experimental approaches to study osmotic stress responses in <it>S. cerevisiae</it> and <it>C. albicans</it>. 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 <it>S. cerevisiae</it>, <it>C. albicans</it> 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.</p> <p><b>Conclusions</b></p> <p>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.</p>