Our research is focused on increasing the understanding at the molecular level of how the essential nutrient, iron, is transported by cells, in particular intestinal cells. Major advances have been made in this area in recent years and our group has been at the forefront of these, identifying two genes (Ireg1/ferroportin and Dcytb) encoding proteins directly involved in the process of duodenal non-heme iron absorption. The genes were isolated from a mutant mouse (hypotransferrinaemic, HPX) which develop anaemia due to lack of a functional transferrin. Due to the anaemia, circulating levels of the iron regulatory peptide hepcidin are low or undetectable in HPX mice, leading to increased iron absorption through the gut (over 10 times higher than wild type mice).  We identified several candidate genes highly over expressed in the gut cells of HPX mice which when tested by Northern blot were highly iron regulated. The first gene to be described from these studies, ferroportin encodes the protein responsible for iron efflux out of intestinal cells, macrophages and other cells and is the only pathway for iron efflux in cells. In humans ferroportin mutations have been found in patients with an iron overload disease similar to haemochromatosis referred to as ferroportin disease disease. Ferroportin is also the target and receptor for the regulatory peptide hepcidin which binds to the transporter and causes its internalisation and degradation.  The ferroportin-hepcidin axis provides an important  mechanism controling iron entry into the body . Dcytb encodes a highly iron-regulated apical ferric reductase that is required to reduce dietary ferric iron to the ferrous form which is transported into the enterocyte by DMT1. In 2005 we identified a gene implicated in duodenal heme transport (HCP1). HCP1 has also been shown to transport folate in the intestine with high affinity and heme with a low affinity. Our group continue to work on identifying other new genes involved in regulating iron metabolism and have recently identified a transcription factor ATOH8 which regulates hepcidin and may lie at the heart of a new iron sensing pathway.

Understanding at the molecular level how iron is absorbed from the diet and trafficked in the body.