the frequency dependence of osmo- adaptation in saccharomyces cerevisiae alexander van oudenaarden...

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The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

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Page 1: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae

Alexander van Oudenaarden Lab

20.309 Final Presentation

Mashaal Sohail

Emily Suter

Page 2: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Motivation

Cells respond to stimuli using complicated systems of biochemical reactions

Systems may comprise of hundreds of reactions

Interest in determining dominant processes that dictate system dynamics

Page 3: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

Page 4: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

cell

Hog1

nucleus

Page 5: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

high osmolarity

solution

Page 6: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

Page 7: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

Page 8: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1 MAPK Pathway

High-Osmolarity Glycerol (HOG) Mitogen-Activated Protein Kinase (MAPK) pathway in budding yeast Saccharomyces cerevisiae

o Core pathway of the hyperosmotic shock response

Page 9: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Experimental Setup

Page 10: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Experimental Setup

Page 11: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Experimental Setup

Page 12: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Experimental Setup

Page 13: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Fourier analysis approximates output signal as sin curve

Page 14: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Linear time invariant model predicts system response to input signal

Hog1 Response to Single NaCl Step

Page 15: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Pulsed-input analysis corresponds to biological network

Page 16: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Hog1-dependent feedback loop plays major role in rapid response

Hog1 Response to Single NaCl Step

Page 17: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Gene expression facilitates response to osmotic shocks on longer time scales

Resp

onse

R(t

)

time [min]

Inhibited Hog1 ExpressionWild Type

Page 18: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Significance/Conclusions

Showed that Hog1 MAPK pathway is governed

by two different response time scales

Demonstrated use of frequency-response

analysis on cellular networks

Utilized engineering principles to predict the

response of dynamic stimuli

Page 19: The Frequency Dependence of Osmo- Adaptation in Saccharomyces cerevisiae Alexander van Oudenaarden Lab 20.309 Final Presentation Mashaal Sohail Emily Suter

Significance/Conclusions

Showed that Hog1 MAPK pathway is governed

by two different response time scales

Demonstrated use of frequency-response

analysis on cellular networks

Utilized engineering principles to predict the

response of dynamic stimuli

Thank you