Abstract:

 Upon an external signal, how do cells decide on changing their fate? How 
 do they time this decision? Cell-to-cell variability in the timing of 
 cell-fate changes can be advantageous for a population of single-celled 
 organisms growing in a fluctuating environment. I'll describe a study on 
 timing variability during such a developmental switch: meiosis in budding 
 yeast, initiated upon nutritional starvation. I combine time-lapse 
 fluorescence microscopy, image analysis and statistical methods to monitor
 the timing of events along the process in thousands of single cells and to
 extract new biological insights from statistical features in the data. I 
 find a large delay and variability before the "point of no return" in this
 process. Cell-cycle variability and nutritional history have little effect
 on this timing variability. Rather, variation in the production rate of 
 the meiotic master regulator Ime1 and its gradual increase over time 
 govern this variability.  I also show that cell size effects are channeled
 through Ime1. These results tie phenotypic variability with expression 
 dynamics of a transcriptional regulator, and provide a general framework 
 for the study of temporal developmental processes. I will also describe 
 follow-up projects using the same system to study information flow in 
 signaling/transcriptional cascades, dynamics of transcription regulation 
 and dynamics of differentiation in mammalian stem cells.