Intravascular haemolysis is the abnormal rupture of red blood cells that causes the release of the haemoglobin (Hb) they contain into the bloodstream, which becomes free plasma haemoglobin (fp-Hb). Various conditions can induce haemolysis, from infectious diseases to genetic and autoimmune disorders. Extracorporeal blood treatments (e.g. dialysis and ECMO) are also often associated with the risk of haemolysis. Free plasma haemoglobin can cause haemoglobinuria (presence of haemoglobin in the urine), renal failure, vasoconstriction and thrombosis; the release of heme and iron from fp-Hb triggers oxidative damage.
As no efficient fp-Hb capture systems are available to date, the aim of the project is to develop a device capable of removing fp-Hb from plasma based on a biomimetic approach inspired by a Staphylococcus aureus bacterial protein called IsdB that specifically and firmly binds human Hb to form an IsdB-Hb complex. The three-dimensional structure of the IsdB-Hb complex will be exploited as a molecular model for the development of peptides and peptidomimetics capable of sequestering fp-Hb.
