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DNA phase-separation as a general mean of regulating gene expression in hybrid cells.

Project Description

Liquid-liquid phase separation is increasingly recognised as a key mechanism to regulate gene expression in living cells by controlling the accessibility of genetic material and its co-localisation with transcription machinery.

Although mechanisms that trigger phase separation in biological cells are not fully understood, a similar control of transcriptional activation could be recapitulated in hybrid cells, engineered from the bottom-up by combining biological and man-made components. Programming the condensation of genetic material (DNA) and its co-localisation with cellular machinery is a particularly promising approach to regulate transcription. DNA aggregation can be induced by well-understood canonical and non-canonical secondary structures, and its occurrence can thus be controlled by a variety of physical stimuli, including temperature, crowding agents and exposure to certain ions.

Herein, we propose to generate a hybrid cell system that can be transcriptionally activated by triggering nucleic-acid phase separation, offering an orthogonal solution to current methods that fully rely on small-molecule treatment (e.g. IPTG) and cannot be controlled easily by physical means. Besides offering an alternative method to regulate gene-expression in artificial cells, this project will yield insights on the fundamental physical processes that might be responsible of gene-regulation via liquid-liquid phase separation in living cells.

Funding Notes

Funded by the Leverhulme Doctoral Scholarship Programme in Cellular Bionics.

Related Subjects

How good is research at Imperial College London in Chemistry?

FTE Category A staff submitted: 54.90

Research output data provided by the Research Excellence Framework (REF)

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