Description du sujet de thèse

The broad goal of the project is to develop a predictive theory of the role of dynamical, spatially extended interactions among multiple enhancers, multiple transcription factors, and multiple promoters for precise gene regulation in eukaryotic development. We will use methods from theoretical nonequilibrium statistical mechanics to explore the constraints that the dynamical nature of the development process imposes on molecular implementations of transcriptional hubs. Our strategy considers different properties of transcription (precision, speed of response) and we will optimize promoter architectures provide optimal solutions. We e will explore this question using evolutionary strategies. We will extend the reasoning from physical constraints and geometry to account for evolutionary constraints. Since not all evolutionary trajectories are always possible, we will compare the constraints the evolution imposes on the promoter architectures assuming an evolutionary cost function that maximizes i) the speed of the promoter readout; ii) precision of the readout. We will compare both the outcomes of the two optimization functions as well as the restrictions on the space of trajectories.

Contexte de travail

The PhD thesis will be carried out in a biophysics team at the Laboratoire de Physique of the Ecole Normale Superieure who has established a long-term collaboration with experimental groups of fly geneticists. They have experience in statisical modeling of biological systems and working both on purely theoretical and data driven problems. The team holds regular meetings. The Ecole Normale Superieure is located in the center of Paris and research in the laboratory is carried out in many topics in physics. This offers and interacting and lively environment.

Contraintes et risques

none