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A new computational strategy to learn how to rationally design novel chromatin nanostructures

The data storage density of DNA inside cells defies anything that humans have achieved so far. In particular, by careful modulation of its three-dimensional structure, DNA can achieve data storage densities of the order of Gigabits per cubic micron. Although breakthroughs in DNA nanotechnology are encouraging, the field has not yet exploited the remarkable way in which cells pack their DNA. Inside cells, DNA forms chromatin, a polymer of cylindrical DNA-protein nanoparticles (nucleosomes) linked by free DNA segments. Fine-tuning the interactions between nucleosomes and DNA enables chromatin to: (1) compress the DNA enormously, by four orders of magnitude for storage, and (2) reorganize its structure on demand to expose specific DNA regions and allow selective DNA access to the cellular machinery. The aim of this project is to elucidate the design principles of DNA data storage in chromatin and translate these principles into design rules for novel sustainable data storage devices. To do this, the student will design, develop, and apply a new coarse-grained chromatin model. Our modelling has already revealed that chromatin has a polymorphic structure. A polymorphic organisation implies that diverse compact chromatin shapes could be produced by careful selection of the distribution of epigenetic modifications, linker DNA lengths, or concentration of additional histone proteins.