Revealing the structure and mechanism of mitotic chromosome folding inside the cell
This project aims to elucidate the folding principles of mitotic chromosomes in single human cells using advanced imaging techniques to enhance understanding of genome restructuring during cell division.
Projectdetails
Introduction
Mitosis is a fundamental biological process every cell undergoes at least once. It requires a dynamic and dramatic restructuring of the genome from extended interphase chromatin to compact individual mitotic chromosomes capable of faithful segregation.
Background
Altered nucleosome interactions, phase separation, and loop extrusion have all been proposed to play important roles in shaping mitotic chromosomes. However, what the internal architecture of single mitotic chromosomes is, and how this architecture is established in space and time by different forces inside the cell remains unclear. This lack of knowledge precludes a comprehensive mechanistic understanding of mitotic chromosome folding and unfolding.
Project Aims
This project aims to resolve the folding principles of chromosomes during mitotic compaction and decompaction in situ, in single human cells.
Methodology
To achieve this, we will:
- Combine newly developed nanoscale DNA tracing technology with quantitative single protein imaging approaches.
- Conduct a systematic structural analysis of mitotic chromosome folding throughout mitosis.
- Investigate when and where which structural features are first established.
- Use targeted, acute perturbations to dissect which regulators are required to form and maintain them.
Expected Outcomes
The resulting data will provide an in situ structure-based model to explain the essential function of the genome in mitosis. It will also allow us to understand the spatio-temporal coordination of the underlying molecular and physical mechanisms.
Conclusion
Overall, the proposed project will provide a new framework for understanding the physiological and pathological roles of mitotic chromosome restructuring during cell division.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 3.118.430 |
Totale projectbegroting | € 3.118.430 |
Tijdlijn
Startdatum | 1-8-2024 |
Einddatum | 31-7-2029 |
Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- EUROPEAN MOLECULAR BIOLOGY LABORATORYpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
MANUNKIND: Determinants and Dynamics of Collaborative ExploitationThis project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery. | ERC STG | € 1.497.749 | 2022 | Details |
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressureThe UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance. | ERC STG | € 1.498.280 | 2022 | Details |
Uncovering the mechanisms of action of an antiviral bacteriumThis project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function. | ERC STG | € 1.500.000 | 2023 | Details |
The Ethics of Loneliness and SociabilityThis project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field. | ERC STG | € 1.025.860 | 2023 | Details |
MANUNKIND: Determinants and Dynamics of Collaborative Exploitation
This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.
Uncovering the mechanisms of action of an antiviral bacterium
This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
The Ethics of Loneliness and Sociability
This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.
Vergelijkbare projecten uit andere regelingen
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
Mechanism, Regulation and Functions of DNA Loop Extrusion by SMC complexesThis project aims to elucidate the molecular mechanisms and regulatory factors of SMC-mediated loop extrusion in DNA, enhancing our understanding of genome organization and its biological implications. | ERC STG | € 1.500.000 | 2023 | Details |
Sequence-structure-function: uncovering how genetic variation at human centromere drives cellular phenotypesThis project aims to investigate centromere variation's mutagenic processes and functional impacts on genome stability and disease predisposition using a multidisciplinary approach. | ERC STG | € 1.500.000 | 2024 | Details |
Learning the dynamic statistical folding of bacterial chromosomesDevelop a data-driven approach to analyze bacterial chromosome organization using Hi-C data, aiming to understand its dynamic folding and impact on functional processes. | ERC COG | € 2.000.000 | 2024 | Details |
Deciphering the role of surface mechanics during cell divisionMitoMeChAnics aims to uncover how cell surface mechanics regulate division by using novel molecular tools and interdisciplinary methods to link structure and function at the cellular level. | ERC COG | € 2.200.287 | 2024 | Details |
Mechanism, Regulation and Functions of DNA Loop Extrusion by SMC complexes
This project aims to elucidate the molecular mechanisms and regulatory factors of SMC-mediated loop extrusion in DNA, enhancing our understanding of genome organization and its biological implications.
Sequence-structure-function: uncovering how genetic variation at human centromere drives cellular phenotypes
This project aims to investigate centromere variation's mutagenic processes and functional impacts on genome stability and disease predisposition using a multidisciplinary approach.
Learning the dynamic statistical folding of bacterial chromosomes
Develop a data-driven approach to analyze bacterial chromosome organization using Hi-C data, aiming to understand its dynamic folding and impact on functional processes.
Deciphering the role of surface mechanics during cell division
MitoMeChAnics aims to uncover how cell surface mechanics regulate division by using novel molecular tools and interdisciplinary methods to link structure and function at the cellular level.