Genome integrity maintenance by liquid-liquid phase separation and oscillations

Name of applicant

Michael Lisby

Title

Professor

Institution

University of Copenhagen

Amount

DKK 16,768,112

Year

2022

Type of grant

Semper Ardens: Advance

What?

The fundamental unit of life is the cell. We will study how cells use liquid-liquid phase separation to organize the biochemical processes of life through formation of biomolecular droplets that concentrate the enzymes and their substrates of each specific process into a confined membrane-less structure.

Why?

It remains largely unknown how liquid-liquid phase separation is achieved and regulated to ensure colocalization of enzymes with their respective substrates in specific biomolecular droplets. We expect that the outcome of this project will fundamentally change our understanding of the complexity of the cell and perhaps even the origin of life.

How?

With the proposed project, we will perform a molecular genetic dissection of liquid-liquid phase separation using DNA repair processes in the cell nucleus as a model to establish a fundamental biological understanding of how biomolecular droplets allow the cell to orchestrate its biochemical processes. We will achieve this through a cross-disciplinary effort that combines state-of-the-art microscopy with biophysical modelling and computational simulations.

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