Iron deficiency and iron deficiency anaemia are major global health issues. Currently available iron supplements based on ferrous iron salts can lead to gastrointestinal side effects. We have developed a new type of oral iron supplement (IHAT) that has been shown in animal studies to be as effective as conventional treatments, but without their limitations. This project will involve investigating the effect of IHAT on the gastrointestinal tract of mice to ensure its safety and to provide preliminary data for future clinical trials in humans.
The overall goals of this project are to investigate in detail how IHAT is taken up by intestinal enterocytes, to examine the effect of oral IHAT on healthy gut epithelial cells and the intestinal microbiome, to determine the effect of oral IHAT on intestinal inflammation and to examine the effect of oral IHAT on intestinal tumourigenesis.
There are several potential components to this project. Characterising the uptake of oral IHAT by intestinal enterocytes will be carried out using knockout animal lines and isolated intestinal loops to determine which proteins and pathways are essential for IHAT absorption. The effect of oral IHAT on gut epithelial cells will be determined by examining markers of inflammation and oxidative stress in enterocytes from wild-type mice. The effect of oral IHAT on the intestinal microbiome of wild-type mice will also be examined using 16s rRNA sequencing. As currently available oral iron supplements are contraindicated in patients with inflammatory bowel disease as they exacerbate symptoms, the effect of oral IHAT will be examined in several mouse models of this disease. The extent of inflammation will be determined by both histological scoring of the intestine and the expression of inflammatory cytokines. Animal models also suggests that currently available iron supplements increase the risk of intestinal tumours. As such various aspects of intestinal tumourigenesis will be examined in mice fed diets containing either ferrous iron or IHAT with particular emphasis on colon cancer development and progression.
Techniques to be used include mouse breeding and dietary manipulation, microscopy and immunohistochemistry, gene and protein expression studies, microbiome analysis and trace element analysis.
- This project can be modified to suit Honours, PhD or Clinical students.
Professor Greg Anderson