Mutational processes and impact of structural variants in somatic cells
The STRUCTOMATIC project aims to catalog and analyze structural variants in human somatic cells to understand their mutational processes and functional impacts on cancer and aging-related diseases.
Projectdetails
Introduction
Mutational processes that generate structural variants (SV) in human and other genomes are understudied and merit attention. Similarly, the functional impact of the SVs on gene function and regulation is also underexplored.
Importance of Structural Variants
SVs may explain some of the missing heritability in population studies. They may provide candidate pathogenic variants in pedigree studies of hereditary diseases, as well as constitute yet-undiscovered driver events that were anticipated from cancer genomics.
Challenges in Studying SVs
Reasons why the SV mutational processes and SV functional impact are understudied are both of a technical and a conceptual nature. Both aspects will be addressed in the STRUCTOMATIC project.
Methodology
We will study structural variation in human somatic cells by combining diverse computational and experimental approaches. This will draw on a genomic resource of hundreds of tumors and healthy tissues sequenced using long-read whole genome sequencing (WGS) that we will generate.
We will further perform mutation accumulation and directed evolution experiments using cell line models of chromosomal instability, generating further genomic data that will support observational analyses of tumor genomes.
Project Aims
The project aims are:
- Thoroughly cataloguing the diversity of SVs in multiple somatic cell types, including those not detectable by short-read WGS.
- Elucidating the underlying mutational mechanisms that generate SVs.
- Investigating their heterogeneity across the human chromosomes as well as their variation between individuals.
- Developing rigorous statistical methodologies for identifying positive and negative selection on SVs in human somatic cells.
Significance
Characterizing the landscape of somatic SVs is crucial for a more complete understanding of the genetic basis of carcinogenesis and of the variable cancer risk across tissues and individuals. It may also provide evidence for hypothesized roles of somatic genetic variation in aging-related pathologies more generally.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.999.428 |
Totale projectbegroting | € 1.999.428 |
Tijdlijn
Startdatum | 1-2-2024 |
Einddatum | 31-1-2029 |
Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- KOBENHAVNS UNIVERSITETpenvoerder
- FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
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 |
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 |
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 |
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.
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.
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.
Vergelijkbare projecten uit andere regelingen
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
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 |
Somatic mutations in vascular-wall function and age-associated diseaseThis project aims to create a detailed atlas of somatic mutations in the arterial wall using single-cell sequencing to understand their role in age-related cardiovascular disease. | ERC ADG | € 2.532.795 | 2024 | Details |
The role of structural genomic variants in eco-evolutionary processesEVOL-SV aims to explore the role of structural variants in genetic diversity and their impact on ecology and evolution, using Coelopa flies as a model to enhance understanding across taxa. | ERC STG | € 1.499.998 | 2023 | Details |
The genomic impact of ancient structural variants on species extinctionThis project aims to analyze ancient genomes of extinct megafauna using advanced sequencing to quantify the impact of structural variants on genome diversity and extinction. | ERC STG | € 1.500.000 | 2024 | Details |
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.
Somatic mutations in vascular-wall function and age-associated disease
This project aims to create a detailed atlas of somatic mutations in the arterial wall using single-cell sequencing to understand their role in age-related cardiovascular disease.
The role of structural genomic variants in eco-evolutionary processes
EVOL-SV aims to explore the role of structural variants in genetic diversity and their impact on ecology and evolution, using Coelopa flies as a model to enhance understanding across taxa.
The genomic impact of ancient structural variants on species extinction
This project aims to analyze ancient genomes of extinct megafauna using advanced sequencing to quantify the impact of structural variants on genome diversity and extinction.