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Architecture and logic of the eukaryotic cell cycle (SYNTHECYCLE)
Date du début: 1 janv. 2013, Date de fin: 31 déc. 2017 PROJET  TERMINÉ 

"Our knowledge of the functioning of eukaryotic cells has emerged from thorough investigation of the molecular mechanisms driving cellular events. However, the complexity of the underlying regulatory networks has made it difficult to understand the core control of essential functions. In the same way that model organisms were chosen for their ease of manipulation or simplicity, model pathways need to be developed to decipher the design principles of regulatory circuits. Using fission yeast, I demonstrated the possibility to replace cell cycle control by a simple synthetic system in vivo and proposed a novel paradigm for the core cell cycle engine. This established the foundation for the proposed projects, which use a synthetic approach to dissect the organisation, complexity and evolution of cellular reproduction.Our work will focus on four axes of research. First, we will investigate the properties of the cyclin dependent kinase (CDK) circuit that ensure reproducibility of cell cycle sequence between cells. Next, we will assess CDK activity dynamics and study their role in progression through cell cycle transitions as well as in the maintenance of population homogeneity. Third, we will investigate the rationale behind the complexity in cell cycle control observed in modern cells, as my previous work has demonstrated that entire branches of the network are dispensable. This will finally lead us to take a unique approach to explore evolutionary principles, assessing how cells operating with simplified CDK circuits adapt and overcome defects in cell cycle progression.These studies relying on mathematical modelling and synthetic rewiring of cell cycle control will shed light on fundamental aspects of this essential process and bring new perspectives to our understanding of its evolution. As cell cycle progression is a foundation of cellular life, our work will have important implications for multicellular organisms and pathological situations."