The regulation of body iron homeostasis

This project is suitable for PhD students.

BACKGROUND

Human conditions with disrupted iron homeostasis are very common and most involve the inappropriate production of the peptide hormone hepcidin, which regulates body iron metabolism. Hepcidin is produced by the liver and secreted into the bloodstream where it acts as a negative regulator of intestinal iron absorption and storage iron release. Prominent examples of conditions associated with altered hepcidin production are the anaemia of inflammation and the iron loading conditions hereditary haemochromatosis and b-thalassaemia.

AIMS

To investigate the pathways regulating hepcidin production and to develop ways to manipulate these pathways to treat disorders of iron homeostasis.

APPROACH

A range of techniques and models will be used to examine the regulation of hepatic hepcidin expression. Various mouse models will be used to determine the involvement of proteins of interest in hepcidin production, including the use of adenovirus and siRNA to alter production. Studies will also be carried out in cultured cells to determine how the proteins regulating hepcidin production interact. Identified pathways can then be targeted in mouse models of human disease to determine whether their manipulation can alter disease progression.

PROJECT POTENTIAL

Inherited iron loading disorders, such as hereditary haemochromatosis and b-thalassaemia, represent some of the most prevalent genetic disorders known and the anaemia of inflammation is the most frequent anaemia in hospitalised and chronically ill patients. The development of new treatments for these conditions would have a major impact on the quality of life for those afflicted with these disorders.