SubsidieMeestersBeyond the chromosome: unravelling the interplay between inter-chromosomal genome architecture and mRNA biogenesis
TRANS-3 aims to uncover the mechanisms and functions of inter-chromosomal genome structure through studying mRNA factories and their regulatory roles in gene expression and disease.
Projectdetails
Introduction
In TRANS-3 we will develop the theoretical and experimental framework to understand inter-chromosomal genome structure and activity. Despite advances in sequencing chromosomes and mapping their three-dimensional (3D) organization, a full picture of 3D genome structure that details how the borders of various chromosome territories functionally interface with one another is still missing.
Analogy
As an analogy, our world map does not indicate most natural corridors or manmade infrastructure that connect countries to one another. Worse, we barely understand how such connections function.
Recent Findings
My recent work has identified one of the few functional inter-chromosomal (trans) DNA interactions known to date: a splicing factory involving over ten chromosomes and orchestrated by the muscle-specific protein RBM20 around its key target, the TTN pre-mRNA.
Hypothesis
I hypothesize that this exemplifies how mRNA biogenesis instructs the formation of trans-interacting chromatin domains (TIDs) around mRNA factories, nuclear compartments that facilitate gene regulation.
Research Objectives
We will test this general hypothesis by dissecting the mechanisms and function of a specific, disease-relevant model: the RBM20 mRNA splicing factory. We will then explore the global impact of these regulations.
Work Packages
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WP1: We will mechanistically assess how mRNA factories form and act through live imaging of the nuclear positioning and alternative splicing dynamics of an RBM20-regulated locus.
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WP2: We will examine the physiological role of mRNA factories by studying the effects of disease-associated mutations in RBM20 and the TTN regulator GATA4, and of genetic variability in TTN regulatory regions.
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WP3: We will develop and deploy a novel pipeline to identify, validate, and study new TIDs and mRNA factories through the combination of molecular biology, bioinformatics, biochemistry, and single-cell biology.
Conclusion
In all, TRANS-3 will venture beyond the chromosome frontier towards a deeper understanding of nuclear structure-function.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.769.998 |
| Totale projectbegroting | € 1.769.998 |
Tijdlijn
| Startdatum | 1-9-2023 |
| Einddatum | 31-8-2028 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- UNIVERSITA DEGLI STUDI DI TORINOpenvoerder
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 |
|---|---|---|---|---|
Understanding the molecular principles governing mRNP architectureThe GOVERNA project aims to elucidate the structure and function of eukaryotic mRNPs by purifying and analyzing their composition using advanced biochemical and imaging techniques. | ERC ADG | € 2.171.250 | 2022 | Details |
Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryosThis project aims to integrate multi-scale dynamics of gene regulation during mammalian embryogenesis using advanced imaging and modeling techniques to enhance understanding of chromatin organization and transcriptional activity. | ERC SyG | € 9.546.410 | 2024 | Details |
Translation in cellular context: Elucidating function, organization and regulation with near-atomic models in whole cellsTransFORM aims to develop novel methods for in-cell structural biology to map ribosome dynamics and regulatory mechanisms in protein synthesis under various cellular conditions. | ERC SyG | € 13.998.670 | 2024 | Details |
Genome topology and mechanical stressThis project investigates how mechanical forces affect chromosome properties and genome integrity, using yeast and mammalian cells to explore nuclear deformations and their implications for diseases. | ERC ADG | € 2.493.665 | 2024 | Details |
Understanding the molecular principles governing mRNP architecture
The GOVERNA project aims to elucidate the structure and function of eukaryotic mRNPs by purifying and analyzing their composition using advanced biochemical and imaging techniques.
Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos
This project aims to integrate multi-scale dynamics of gene regulation during mammalian embryogenesis using advanced imaging and modeling techniques to enhance understanding of chromatin organization and transcriptional activity.
Translation in cellular context: Elucidating function, organization and regulation with near-atomic models in whole cells
TransFORM aims to develop novel methods for in-cell structural biology to map ribosome dynamics and regulatory mechanisms in protein synthesis under various cellular conditions.
Genome topology and mechanical stress
This project investigates how mechanical forces affect chromosome properties and genome integrity, using yeast and mammalian cells to explore nuclear deformations and their implications for diseases.