SubsidieMeestersMetastable Epiallele: Role of Epigenetic Variability for the Development of Metabolic and Endocrine Diseases
This project aims to identify and characterize metastable epialleles in humans to understand their role in metabolic diseases, using advanced technologies on postmortem samples and stem cells.
Projectdetails
Introduction
The development of obesity in industrial and low-and middle-income countries is leading to a severe burden for patients and health care systems based on associated comorbidities such as cardiovascular diseases and type 2 diabetes mellitus.
Role of Epigenetics
Apart from the genetic background, epigenetic modifications like DNA methylation are supposed to play an important role in body weight regulation. So far, epigenome-wide association studies have not been able to elucidate this relationship, as most methylation differences were related to a genetic variant.
Importance of POMC Gene
The identification of the POMC (pro-opiomelanocortin) gene, a key factor for hypothalamic body weight regulation, as a metastable epiallele in humans, is important for understanding how methylation variability affects the individual phenotype.
Characteristics of Metastable Epialleles
Metastable epialleles are:
- Methylome-regions that are non-genetically determined
- Stochastically regulated and set in early embryonic development
- Non-tissue specific, stable over time, and modified by Carbon-1 metabolites in utero
However, their role in human diseases remains unclear.
Research Objectives
Within this application, I aim to elucidate and characterize how epigenetic modifications such as metastable epialleles modulate human susceptibility and predisposition to metabolic and endocrine diseases, as well as analyze the impact of environmental factors.
Proposed Methodology
To achieve this goal, I propose a unique approach using advanced technologies to:
- Analyze human postmortem samples
- Utilize human embryonic stem cells to identify new metastable epialleles in humans
- Elucidate new mechanisms and relationships between phenotypic variation and methylation variability
The combination of the algorithm to identify methylation variability and the use of stem cell models to functionally characterize epigenetic variants will serve as a blueprint for analyzing the epigenetic contribution to other endocrine, neurological, or cardiovascular diseases.
Conclusion
This research will generate a powerful resource for researchers worldwide.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.997.969 |
| Totale projectbegroting | € 1.997.969 |
Tijdlijn
| Startdatum | 1-2-2023 |
| Einddatum | 31-1-2028 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- CHARITE - UNIVERSITAETSMEDIZIN BERLINpenvoerder
Land(en)
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