Multiple fission cycles in Chlamydomonas

In this talk I will present a "dynamical paradigm" for modeling networks of interacting genes and proteins that regulate every aspect of cell physiology. The paradigm is based on dynamical systems theory of nonlinear ODEs, especially one- and two-parameter bifurcation diagrams. I will show how we have used this paradigm to unravel the mechanisms controlling "multiple fission" cycles in the photosynthetic green alga Chlamydomonas. While most eukaryotic cells maintain a characteristic size by executing binary division after each mass doubling, Chlamydomonas cells can grow more than eight-fold during daytime before undergoing rapid cycles of DNA replication, mitosis and cell division at night, which produce up to 16 daughter cells. We propose that this unusual strategy of growth and division (which is clearly advantageous for a photosynthetic organism) can be governed by a size-dependent bistable switch that turns on and off a limit cycle oscillator that drives cells through rapid cycles of DNA synthesis and mitosis. We show that this simple ‘sizer-oscillator’ arrangement reproduces the experimentally observed features of multiple-fission cycles and the response of Chlamydomonas cells to different light-dark regimes. Our model makes unexpected predictions about the size-dependence of the time of onset of cell-cycle oscillations after cells are transferred from light to dark conditions, and these predictions are confirmed by single-cell experiments.

Collaborators: Stefan Heldt and Bela Novak (Oxford Univ) on the modeling; Fred Cross (Rockefeller Univ) on the experiments.