Objective
Histones are the elemental building blocks of chromatin and must be produced in vast amounts to support chromatin structure and integrity. DNA replication further necessitates a rapid doubling of histone content to enable packaging of nascent DNA. To meet this formidable demand, cells not only encode constitutively expressed histone genes, but also DNA replication-dependent histone genes transcribed within specialized subnuclear histone locus bodies. Expression of these histone genes must be dynamically regulated to match the acute demands of the genome and avoid detrimental imbalances in histone supply. Importantly, recent work revealed that the main function of amplified transcription that is ubiquitous in cancer is to elevate histone production fueling faster cell proliferation, thus dysregulated histone biogenesis may be a novel pervasive cancer driver, with major ramifications for precision oncology. However, despite their vital roles in cell biology and emerging key impact on human disease, the architecture, mechanisms and regulation of histone biogenesis machineries remain highly underexplored. Rectifying this knowledge gap is therefore of paramount importance. Rooted in my recent discoveries and extensive pilot data revealing novel paradigms governing histone biogenesis, this research program will pioneer comprehensive profiling of the gene and protein networks underpinning histone production in human cells, empowered by an unparalleled discovery pipeline integrating transformative phenotypical CRISPR screening, quantitative proteomics, systematic protein interaction modeling and in-depth mechanistic studies. Building on these insights, I will address how histone supply is dynamically tailored to demand by the cell cycle, feedback control and genotoxic stress, and how its targeted or cancer-associated deregulation shapes epigenome maintenance and cell physiology, to holistically unravel a fundamental but relatively overlooked dimension of chromatin biology.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
You need to log in or register to use this function
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
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.
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.
Funding Scheme
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.
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
See all projects funded under this callHost institution
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.
2100 Koebenhavn
Denmark
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.