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Rebuilding interphase nuclei into mitotic chromosomes

Objective

"The remarkable morphological transformation that cells undergo during mitosis has been studied for >140 years, but how mitotic chromosomes are built from interphase nuclei remains unknown and challenging to study. We propose to uncover the mechanisms for this process at high-resolution in cells and in vitro, a task that requires coordinated implementation of innovative experimental designs in several disciplines. We will engineer mutant and hybrid cell lines that enter mitosis with minute-by-minute synchrony, allowing us to develop new “kinetic sectioning” methods to map the intracellular distribution of chromatin near the nuclear envelope, from nucleosomes to mitotic chromosomes at unprecedented resolution, trace the action of individual condensin complexes as they produce loops during mitotic chromosome formation and efficiently isolate mitotic chromosomes for biochemical (4D proteomics) and structural analysis. We will combine genome-wide chromatin mapping, super-resolution microscopy and cryo-ET with innovative image analysis and modelling. In addition to studies of conventional chromosomes, we will study tiny natural ""dot chromosomes"" from chicken cells. Only a few megabases in size, these natural models for their larger counterparts will be isolated for detailed 4D proteomic and structural analysis and used to map scaffold and loop organisation at high resolution. Our team will address mitotic chromosome formation from multiple complementary angles in a synergistic approach where insights from collaborative computational analysis, cross-linking and structural data will inspire and define questions, both predicted and unforeseen. We will discover new insights as condensed mitotic chromosomes are built from active interphase chromatin across a wide range of physical and temporal dimensions. The information and technology that we develop will be generally applicable to other cellular systems, contributing to a paradigm change in structural and cellular biology.
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Keywords

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Programme(s)

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Topic(s)

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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.

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2025-SyG

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Host institution

UNIVERSITAT ZURICH
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.

€ 3 237 426,25
Address
RAMISTRASSE 71
8006 Zurich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
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.

€ 3 237 426,25

Beneficiaries (4)

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