RNA/DNA base modifications
We study enzymes involved in the metabolism of nucleic acids, how they operate in cells and the roles they play in maintaining organismal health. We are particularly interested in enzymes acting on edited or damaged RNA/DNA bases. Originally the focus was proteins involved in DNA repair, but we have now expanded to also include enzymes with activity on RNA. One example is Endonuclease V (EndoV) which is a DNA repair for inosines in bacteria, whereas it acts on RNA in humans. We use methods ranging from molecular biology and cell biology to knock-out organisms (yeast and mouse). Our work on EndoV has yielded some fascinating findings; in three different disease models, namely liver cancer, atherosclerosis and stroke, mice that lacked EndoV did better than wild-type control mice. We are currently investigating whether this is related to dysregulation of macrophage function due to altered levels of small non-coding RNA. Immune cells are also central in another project where adenosine deaminase 2 (ADA2) is studied. Deficency in this enzyme (DADA2) gives a severe condition with immune defects, vasculitis and frequently strokes. Our research has led to the discovery of novel enzyme activities for ADA2, opening up new diagnostic and treatment avenues for this often life-threatening disease.