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Phase Separation and Oscillations in DNA Damage Response

Objective

DNA damage response is a crucial function in living organisms, essential for maintaining genomic integrity. Two key processes prevent damage from propagating through generations: 1) DNA repair and 2) regulation of the cell cycle. Recent discoveries reveal that following DNA double-strand breaks, cells form biomolecular condensates at the site of damage through liquid-liquid phase separation. Another hallmark of the response is the initiation of oscillatory p53 concentration leading to cell cycle arrest. Despite being one of the most basic responses in cells, the physical mechanisms underlying this remains poorly understood as does the interplay between repair and regulation.
I aim to derive the basic principles for condensates interacting with dynamical and oscillatory concentration fields. Here I will uncover how cells use fundamental mechanisms of physics to control formation and maintenance of condensates and how the emergence of oscillations can facilitate this task.
The main highlights of PHOSCIL are the following:
Revealing the physical mechanisms and inferring observables of condensate formation, by creating new methods for analysis, guided by theoretical models applied to novel experiments.
Discovery of out-of-equillibrium phenomena of oscillatory and dynamic fields and their interactions with phase separation, generating conceptual advances in our understanding of biophysical systems.
Uncovering the functional roles of phase sparation and oscillation on both repair and cell cycle regulation, advancing our fundamental understanding of, and ability to influence, cell fate decisions.
To succesfully take these ambitious steps, I will combine theory and experiments that, taken together, will uncover novel concepts in the physics of phase separating systems and define a new chapter in our understanding of the DNA damage response.

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Keywords

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2025-STG

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Host institution

KOBENHAVNS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 497 672,00
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 497 672,00

Beneficiaries (1)

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