Samuel D. Acquah & Arvind Thiagarajan The effects of molecular noise and size control on variability in the budding yeast cell cycle Di Talia et al., Center for Studies in Physics and Biology Rockefeller University, New York, NY Nature 2009 20.309 Presentation 8 December 2011 Samuel D. Acquah & Arvind Thiagarajan

Cell Cycle in Yeast

Motivation Conventional Theory – G1 Length controlled by deterministic cell size requirement Significant variation in G1 timing among cells of same size invalidates this New model – both cell size (deterministic) and gene expression (stochastic) control G1 length Wanted to make a model that accounted for this additional variation among cells with the same size

Measurements Yeast transformed with Myo1-GFP fusion DsRed RFP under control of ACT1 promoter

Validation of Size Measurement DsRed grows exponentially in time and scales proportionally with both ploidy and geometric size estimates

Timers v. Sizers Timer – G1 time independent of size at birth Mother Cells (slope = -0.1) Sizer – G1 time exponential in size at birth Daughter Cells (slope = -0.4, -0.7)

Deviations from Size Control Mechanism Assume G1 time is sum of size control term, associated noise, and noise not correlated with size Uncorrelated noise consistently greater than size correlated noise Is this uncorrelated noise due to gene expression?

Two Stages for G1

Validation of Two Stage Model

Conclusion G1 duration in budding yeast determined by trafficking and activity of Whi5 Nuclear Whi5 -> Size Dependent Deterministic Control + Gene Expression Noise Cytoplasmic Whi5 -> Size Independent Constant Time + Gene Expression Noise