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Stochasticity Open Seminar April 4, 2017, 12:00

Open Seminars of the Research Group on


Stochasticity and Control in the Dynamics and Diversity of Immune Repertories: an Example of Multi-Cellular Co-Operation


Tuesday, April 4, 2017, 12:00

at the Israel Institute for Advanced Studies, Room 128




Yeast response to multiple carbon sources: a case study of combinatorial signal integration


Yoni Savir (Technion) 


A major determinant of the fitness of biological systems is their ability to integrate multiple cues from the environment and coordinate their metabolism and regulatory networks accordingly. While much is known about the response to a single stimulus, our understating of combinatorial integration of multiple inputs is still limited. As a model system, we studied how yeast responds to hundreds of mixtures of preferred carbon source, glucose, and a less preferred one, galactose. Many of the components of this response, known as catabolite repression, are conserved from yeast to human. We found that, in contrast to the textbook view, instead of simply inhibiting galactose utilization when glucose is above a threshold concentration, individual cells respond to the ratio of glucose and galactose, and based on this ratio determine whether to induce genes involved in galactose metabolism. We investigate the genetic architectures that can result in a ratio sensing and how these architectures provide a fitness advantage which could have shaped the evolution of this property.



Related Research Questions


  1. How does combinatorial nutrient sensing change as the cells age? Can we reverse nutrient sensing failure?
  2. What types of biological circuits allow coping with high-dimensional input space?
  3. What (if any) are the optimal switching strategies when a system changes its output behaviors based on multiple inputs? For instance when cells change metabolic gene programs in the presence of preferred and less preferred resources.



Suggested Reading


Achieving global perfect homeostasis through transporter regulation (2017)
Savir, Y., Martynov,A, Springer M. 
Plos Comp Bio


Competitive Inhibition Can Linearize Dose-Response and Generate a Linear Rectifier (2015)
Savir, Y., Tu, BP, Springer, M.  
Cell Systems


Galactose metabolic genes in yeast respond to a ratio of galactose and glucose (2015)
Escalante R.*, Savir, Y.*, Carroll, SM., Ingraham, J.B., Wang, J., Marx, C.J., and Springer, M. 
Proc Natl Acad Sci USA 112(5): 1636-1641.



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