The control of iron availability for cell utilisation is dependent on cellular receptors and iron-binding proteins. Two of the most important receptors are transferrin receptor 1 (TFR1), the receptor involved in iron uptake, and its homologue TFR2, expressed at high levels in the liver, which is involved in cellular iron regulation. The Hepatogenomics Research Group has developed many unique knockout mice to help us understand the role of TFR2. These include whole body, hepatocyte-specific, and macrophage-specific knockouts of TFR2. In addition, the floxed-TFR2 mice generated by our Group is in use by several researchers internationally to understand more tissue-specific functions of TFR2.
Specifically, this project seeks to address the hypothesis that cell-specific trafficking of transferrin receptors contributes to their specific cellular role in liver and erythroid cells. The project will delineate the biology of two important receptors that transport and regulate iron, an element essential for life and many cellular processes.
This project aims to understand the how TFR1 and TFR2 are trafficked in the liver and erythroid cells and how this contributes to tissue and cell-specific functions; specifically if there is differential trafficking of TFRs within the liver and erythroid cells by sorting nexins, and other vesicular trafficking adaptor molecules and how this modulates their activity.
This project will use many molecular and cell biology techniques, mass spectrometry, and state-of-the-art microscopy to answer these questions. Expected outcomes include determining the role of erythroid and hepatic Tfr2 in erythroid development and hepatic hepcidin regulation.