Project description
Physics of the DNA damage response
The DNA damage response mechanism is responsible for maintaining genomic integrity and preventing harmful mutations from being passed on to daughter cells. This mechanism involves DNA repair mediated by proteins that accumulate at DNA double-strand breaks, as well as through the initiation of cell cycle arrest. Despite its importance, little is known about the physical mechanisms driving the DNA damage response. The ERC-funded PHOSCIL project aims to address this gap in knowledge by investigating how proteins interact to form condensates. The goal is to understand the physical principles that regulate repair and cell cycle control, and how they shape crucial cell fate decisions.
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-STG
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1165 KOBENHAVN
Denmark
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