Genes are switched ‘on' or ‘off' during development epigenetically, by binding of proteins to DNA and addition of chemical tags to both DNA and proteins. While present in all cells of the human body, the human ß-globin locus regulates the switch from fetal (?-globin) to adult (ß-globin) hemoglobin during development in the red blood cells only. The switch is meant to optimize oxygen use during gestation, and relies on DNA regions and proteins that fold the DNA and control the access of other proteins to the globin genes. Here, we aim to study how DNA folding and accessibility changes during hemoglobin switching using advanced sequencing methods that inform about the openness and conformational structure of the DNA. By editing DNA with genome engineering techniques (i.e. CRISPR), we'll identify DNA regions critical for globin gene regulation. Our goal is to reactivate the fetal ?-globin by epigenome editing as a safer and lasting treatment for sickle cell disease and ß-thalassemia.

2025

2029