Universiteit Leiden

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Research project

Unfolding the principles of genome folding and dynamics in bacteria

What are the principles of genome folding and dynamics in bacteria?

Remus Dame
Human Frontier Science Program Human Frontier Science Program

All living organisms must organize their DNA within the confines of the cell. This is achieved by a combination of “passive” factors (e.g. cell size and shape) and “active” processes (e.g. DNA folding proteins). While much is known about how DNA is organized in higher organisms, we still have little understanding of the DNA folding processes that drive chromosome organization and compaction in bacteria. Given the abundance of these organisms, and their impact on human activity, this represents a startling gap in our knowledge. In recent years nano-scale cell imaging, large-scale genomic techniques, and mathematical/physical modeling of biopolymers have emerged as new tools to study DNA biology. In this program we bring together these approaches to facilitate precise dissection of bacterial chromosome structure. Thus, in a collaborative effort between theory and experiment, we will test and expand models to describe bacterial genome organization.

The leading model in the field is that the Escherichia coli chromosome is organized into loops. These loops are thought to be actively stabilized by DNA bridging proteins. It has long been known that bacteria radically re-model their chromosomes in response to environmental stress such as changes in nutrient availability. Strikingly, this re-modeling coincides with major adjustments in the cell’s pool of DNA folding proteins and, at times, dramatic changes in cell shape and composition. Thus, we hypothesize that the organization of bacterial chromosomes is highly dynamic and influenced by both active and passive processes associated with changing growth rate. To test this hypothesis we will take inventories of DNA organization during periods of cell growth and starvation. We will then perform iterative cycles of modeling and experimental testing. We expect to reveal distinct DNA-folding mechanisms employed by bacteria in different growth phases.

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