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The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisae

Phillip Samayoa 20.309 – Paper Presentation October 9, 2008. The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisae. Jerome T. Mettetal , Dale Muzzey , Carlos Gómez - Uribe , Alexander van Oudenaarden. Introduction. Objective

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The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisae

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  1. Phillip Samayoa 20.309 – Paper Presentation October 9, 2008 The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisae Jerome T. Mettetal, Dale Muzzey, Carlos Gómez-Uribe, Alexander van Oudenaarden

  2. Introduction • Objective • Determine the dominant processes of yeast’s response to osmotic shock • Approach • Systems-engineering methods • Back out a predictive model of signaling dynamics • Significance • Improved understanding of MAPK’s role in osmotic regulation • New approach to developing cellular models

  3. High Osmolarity Response • Less glycerol export (FPS protein) • HOG1 MAPK is transported to the nucleus • indication of osmotic stress • transcription • Measurement of Osmotic Stress • HOG1 tagged with YFP • Nuclear Protein tagged with RFP • (<YFP>nuclear/<YFP>cell)population

  4. Input Stimulus & Measure Output

  5. Fourier Analysis Extracts a Predictive Model • \ Example (RC circuit): Input = Vo*sin(wt) Vout = sin(wt)*Vo(1 + iwRC)-1

  6. The Backed out Model can Predict the Cell’s Step Response

  7. The LTI Model can be Converted into a Molecularly defined Model

  8. Mutant Strain Showed Delayed Short-Term Response Dynamics

  9. Gene Expression Mediates Response Over Longer Time Scales Cells can synthesize proteins Cells can’t synethsize proteins

  10. Summary • Engineering principles to predict response of a system • Moving Forward • Measure state-space variables

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