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Disentangling metaphase chromosome organisation one chromosome at a time

Project description

Studying the architecture of metaphase chromosomes

Chromosomes acquire their most compact state just before separation during metaphase. The EU-funded MONOCHROME project aims to develop an approach that allows real-time super-resolution imaging and manipulation of entire non-fixed metaphase chromosomes under near-physiological conditions. Researchers propose to obtain quantitative images of the proteins that establish the architecture of metaphase chromosomes and analyse the internal protein dynamics at the molecular level. The introduction of force-induced expansion microscopy, together with advanced labelling and imaging techniques, will make possible the validation and correction of the current models of metaphase organisation as well as an exploration of the physical properties of chromosomes and chromosome separation dynamics.

Objective

Chromosomes assume their most compact state during metaphase just before they are separated. In this process of cell
division the chromosomes experience high forces and genomic defects can occur then. Many techniques have built
considerable understanding of metaphase chromosome structure and a multitude of models have been put forward how
cells organize their chromosomes during metaphase. Yet, given the complexity of the process and limitations of the methods
to study them, it is far from being fully understood. The breakthrough opportunity in this regard is the development of tools
that allow real-time, 3D, super-resolution imaging and manipulation of entire non-fixed metaphase chromosomes under nearphysiological
conditions.
Here I propose to quantitatively image the proteins that establish the architecture of metaphase chromosomes and
disentangle the connection between its architecture, internal protein dynamics and mechanics at the multi-protein as well as
the single-molecule level. For this project I plan to expand the combination of optical manipulation and fluorescent
microscopy by introducing force-induced expansion microscopy together with advanced labeling and imaging techniques
that ultimately will permit real-time, 3D, super-resolution quantitative analysis of complex (protein) structures within native
non-fixed metaphase chromosomes. With this kind of instrument it becomes possible to validate and/or challenge the current
models of metaphase organization as well as explore the physical properties of chromosomes but also study chromosome
separation dynamics.
My extensive experience handling biological systems and pushing instrumental boundaries gives me an excellent starting
point to address key research questions with regards to metaphase chromosomes. In doing so I can improve our
understanding of chromosome organization which is important because chromosome defects can have devastating
consequences leading to for example cancer or fragile X syndrome.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2019-ADG

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Host institution

STICHTING VU
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.

€ 1 997 284,00
Address
DE BOELELAAN 1105
1081 HV Amsterdam
Netherlands

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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.

€ 1 997 284,00

Beneficiaries (1)

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