Study level

  • Vacation research experience scheme

Faculty/School

Topic status

In progress.

Research centre

External supervisors

  • Associate Professor David Frazer, QIMR Berghofer

Overview

Iron is an essential nutrient, but is also toxic when in excess, so the amount of iron in the body must be tightly controlled. As mammals don’t actively excrete iron, body iron levels are regulated at the point of absorption in the small intestine. This process is controlled by the hormone hepcidin which is secreted by the liver in response to iron requirements.

Circulating hepcidin binds to the iron export protein ferroportin on intestinal cells, causing the protein complex to be internalised and degraded, reducing iron absorption from the diet. Inappropriate regulation of hepcidin production causes a number of human diseases.

The most common of these is hereditary haemochromatosis, which results from mutations in the HFE gene. This leads to a reduction in hepcidin production, increasing dietary iron absorption and causing tissue iron loading. Currently, the only treatment for hereditary haemochromatosis is regular phlebotomy to remove the excess iron.

This project will examine the molecular processes regulating hepcidin production and will establish tools for examining novel treatments for hereditary haemochromatosis.

Aims

This project aims to:

  1. utilise cultured cells to examine the factors regulating hepcidin production
  2. establish a high throughput assay to screen for novel iron removing compounds.

This research will be carried out at QIMR Berghofer (Herston).

Research activities

Research activities include:

  • laboratory experiments
  • data collection
  • data analysis.

In aim 1, liver cells in culture will be treated with a range of compounds to determine their effect on hepcidin production.

In aim 2, cells stably expressing yellow fluorescent protein (YFP) under the control of an iron responsive element will be created, allowing YFP to be regulated by cellular iron levels.

In future studies, this cell line will be used as part of a high throughput assay to screen compound libraries for novel molecules able to remove iron from cells.

Outcomes

This study should provide more information about the molecular processes regulating hepcidin expression, which could potentially assist in the development of agents to treat disorders of iron homeostasis, such as hereditary haemochromatosis.

You can expect to gain a range of skills in molecular biology, tissue culture and protein analysis, as well as data analysis and presentation skills.

Skills and experience

You should have a basic knowledge of molecular biology.

Keywords

Contact

Contact David.frazer@qimrberghofer.edu.au for more information.