α-Globin
Globin-trotting
Hemoglobin is one of the most important proteins in humans, responsible for carrying oxygen in red blood cells throughout our body. Genetic diseases involving hemoglobin, known as thalassemia, affect hundreds of millions of people around the world. Hemoglobin is composed of four protein subunits, two each of α-globin and β-globin, and thalassemia can arise due to defects in either of these subunits (α-thalassemia and β-thalassemia respectively). These defects typically result in reduced production of the protein, and so it is crucially important to study how their expression is regulated. Furthermore, expression of the globin genes has served as a model for studying gene expression in general, with multiple genetic elements involved in the process that are now believed to be common to the majority genes.
We are using our technology, in collaboration with Dr. Douglas Higgs, a leader in the fields of α-globin genetics and α-thalassemia, to build many variants of the α-globin gene region. These synthetic variants will be used by the Higgs lab to replace the naturally-occurring α-globin gene in mice and mouse cell lines in order to explore their effects on the production of α-globin. This approach will allow us to gain invaluable insight into the underlying causes of α-thalassemia, help develop strategies to correct the disease, and further our understanding of how gene expression is regulated in general.
Read more: Blaney et al., Cell. 2023.
IN COLLABORATION WITH:
Douglas Higgs, PhD, University of Oxford