Summary
The human hematopoietic system is a paradigmatic, stem cell-maintained organ with enormous cell turnover. Hundreds of billions of new blood cells are produced each day. The process is tightly regulated, and susceptible to perturbation due to genetic variation.
In this project, we will explore an innovative, population-genetic approach to find regulators of blood cell formation. Unlike traditional studies on hematopoiesis in vitro or in animal models, we will exploit natural genetic variation to identify DNA sequence variants and genes that influence blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples from the experiments that nature has performed during evolution.
Building on our previous work, unique population-based materials, mathematical modeling, and the latest genomics and genome editing techniques, we will:
1. Develop high-resolution association data and analysis methods to find DNA sequence variants influencing human hematopoiesis, including stem- and progenitor stages.
2. Identify sequence variants and genes influencing specific stages of adult and fetal/perinatal hematopoiesis.
3. Define the function, and disease associations, of identified variants and genes.
Led by the applicant, the project will involve researchers at Lund University, Royal Institute of Technology and deCODE Genetics, and will be carried out in strong environments. It has been preceded by significant preparatory work. It will provide a first detailed analysis of how genetic variation influences human hematopoiesis, potentially increasing our understanding, and abilities to control, diseases marked by abnormal blood cell formation (e.g., leukemia).
In this project, we will explore an innovative, population-genetic approach to find regulators of blood cell formation. Unlike traditional studies on hematopoiesis in vitro or in animal models, we will exploit natural genetic variation to identify DNA sequence variants and genes that influence blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples from the experiments that nature has performed during evolution.
Building on our previous work, unique population-based materials, mathematical modeling, and the latest genomics and genome editing techniques, we will:
1. Develop high-resolution association data and analysis methods to find DNA sequence variants influencing human hematopoiesis, including stem- and progenitor stages.
2. Identify sequence variants and genes influencing specific stages of adult and fetal/perinatal hematopoiesis.
3. Define the function, and disease associations, of identified variants and genes.
Led by the applicant, the project will involve researchers at Lund University, Royal Institute of Technology and deCODE Genetics, and will be carried out in strong environments. It has been preceded by significant preparatory work. It will provide a first detailed analysis of how genetic variation influences human hematopoiesis, potentially increasing our understanding, and abilities to control, diseases marked by abnormal blood cell formation (e.g., leukemia).
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/770992 |
| Start date: | 01-10-2018 |
| End date: | 30-09-2024 |
| Total budget - Public funding: | 2 000 000,00 Euro - 2 000 000,00 Euro |
Cordis data
Original description
The human hematopoietic system is a paradigmatic, stem cell-maintained organ with enormous cell turnover. Hundreds of billions of new blood cells are produced each day. The process is tightly regulated, and susceptible to perturbation due to genetic variation.In this project, we will explore an innovative, population-genetic approach to find regulators of blood cell formation. Unlike traditional studies on hematopoiesis in vitro or in animal models, we will exploit natural genetic variation to identify DNA sequence variants and genes that influence blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples from the experiments that nature has performed during evolution.
Building on our previous work, unique population-based materials, mathematical modeling, and the latest genomics and genome editing techniques, we will:
1. Develop high-resolution association data and analysis methods to find DNA sequence variants influencing human hematopoiesis, including stem- and progenitor stages.
2. Identify sequence variants and genes influencing specific stages of adult and fetal/perinatal hematopoiesis.
3. Define the function, and disease associations, of identified variants and genes.
Led by the applicant, the project will involve researchers at Lund University, Royal Institute of Technology and deCODE Genetics, and will be carried out in strong environments. It has been preceded by significant preparatory work. It will provide a first detailed analysis of how genetic variation influences human hematopoiesis, potentially increasing our understanding, and abilities to control, diseases marked by abnormal blood cell formation (e.g., leukemia).
Status
SIGNEDCall topic
ERC-2017-COGUpdate Date
27-04-2024
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