Seminar by Liedewij Laan   FAS Center for Systems Biology at Harvard University 
Time: 16 December 14.00h – 14.30h (followed by a 10 minute question round)
Place: F105  

Title: How robust is the yeast polarization machine to genetic perturbations?  
Abstract:
Cells are highly organized through complex gene regulatory and protein networks for faithful and precise function. These networks also need to be robust to genetic perturbations. Large multi-cellular organisms, in particular, need to buffer against spontaneous mutations to avoid, for example, cancer formation. Nevertheless, on long evolutionary timescales mutations are essential as they allow organisms to adapt to their changing environment. So, how robust are these complex networks to genetic perturbations (current research), and how do they manage to be both robust and highly organized on short cellular timescales, but also adaptable on long evolutionary timescales (future)? I addressed these questions by studying the establishment of polarity in the simple, single-celled organism, budding yeast. Polarity establishment is an essential process: it ensures formation of a single site of polarization which determines the location of the next daughter cell. I strongly perturbed this functional network by removing the nearly essential gene BEM1. After deleting BEM1 the cells are dramatically sick, resulting in a ~10-fold reduction in population growth rate. I evolved these cells by serial dilutions for one thousand generations. Initially the cells rapidly increased their growth rate, followed by a phase of slow increase, approaching the wild-type growth rate. In addition, several phenomenological properties of the mutants, which were initially strongly perturbed, evolved back to wild-type. In the future, I would like to relate these phenomenological changes in cell physiology to specific molecular changes.