Start of funding 01.07.2016

Computational Investigation of Cellular Heterogeneity in the Gal pathway in S. Cerevisiae

Prof. Dr. Fabian Theis
Technische Universität München
Dept. of Mathematik - Institute of computational biology (ICB)

Prof. Dr. Hana El-Samad
University of California, San Francisco
Dept of Biochemistry



In many species, isogenic cells respond to an identical stimulus with different responses. As an example, the budding yeast S. Cerevisiae shows a heterogeneous response to a mixture of glucose and the less preferred sugar galactose. One subpopulation of cells induces the galactose metabolism machinery before the glucose is depleted, resulting in slower growth but shortened lag phase upon glucose depletion. Possible explanations include deterministic bistability of the network and/or intrinsic stochasticity of gene expression. We propose to investigate the source of observed heterogeneity in the Gal network by combining novel modeling and computational techniques such as the Method of Conditional Moments and the ODE-constrained mixture. Better understanding the source of this heterogeneity would shed light on the biophysical mechanisms that constrain how cells navigate tradeoffs between present and future fitness.

Final report:
Due to staff shortages the project could not be conducted as planned and was terminated prematurely.