Genetic variation exposes regulators of blood cell formation in vivo in humans
|Title||Genetic variation exposes regulators of blood cell formation in vivo in humans|
|Sponsor||European Research Council (ERC)|
|Institution||University of Lund|
Associated cell lines
Our aim is to 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).