Mini Course: Biophysical Principles of Regulation in Bacteria

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Bacteria operate at molecular scales where thermal fluctuations are significant. Consequently, they deploy a wide range of regulatory strategies, either to reduce the effects of noise or, when possible, to exploit it to their own advantage. This course introduces a selection of such strategies, describing the theoretical methods and experimental techniques used to study them. The course is organized into four independent parts. The first part will be devoted to quantitative models of molecular control, including allostery, kinetic proofreading, enzyme kinetics and the statistical physics of ligand binding. We will then examine how bacteria manage to coordinate their cycle of DNA replication with the growth cycle in different conditions. The third part focuses on regulatory mechanisms that govern the response to thermal stress (both heat shock and cold shock). Finally, we will explore gene-regulatory processes in bacterial flagellar systems. The course is presented as 4 weeks of 2 hour classes. There are no formal prerequisites, although basic knowledge of cell biology and statistical physics may be useful.

Contents

1. Quantitative models of molecular control. Allostery (MWC), kinetic proofreading, enzyme kinetics, statistical physics of ligand binding.
2. DNA replication and initiation timing accuracy. Structure of the replication origin, the Cooper–Helmstetter model, DnaA and initiation titration model.
3. Regulatory adaptation to thermal stress. Thermal growth curves, protein folding, heat shock response, cold shock proteins.
4. Flagellar systems and gene regulation of flagellar genes. Run-and-tumble behavior, structure of the bacterial flagellum, regulation through different classes of gene promoters.