- This project can be modified to suit Honours, PhD or Clinical students
An adequate supply or iron is essential for normal health, and disturbances in iron metabolism represent a significant class of human diseases. Biochemical tests for measuring iron status are among the most frequently requested by doctors, but current methods for measuring body iron levels are far from ideal. The main limitation is that the most of the tests for measuring body iron are also influenced by inflammation. A good example of this is the serum ferritin test. As the incidence of obesity rises in our population we are seeing more and more instances of high serum ferritin that are not related to high body iron. This is because obesity is an inflammatory condition. While correction of iron status markers for inflammation can be carried out, this is not always reliable and requires multiple tests to be conducted.
The major goal of this project is to seek one or more robust and reliable markers of iron status that are not influenced by inflammation. A secondary goal is to develop a point of care assay based on this (or these) molecules.
This project will consist of two main components. The first will be the discovery phase and will be carried out using mice. Using an experimental model like the mouse will enable us to precisely control conditions so that we can distinguish between iron-related effects and inflammation related effects. Animals will be maintained on diets of differing iron content, or subjected to various inflammatory stimuli (including a high fat diet). Plasma samples will be collected and analysed using a contemporary proteomics approach to seek differences between the various conditions. Depending on the initial results, we may also extend this to analyse the plasma metabolome. We will identify molecules that are influenced by iron status, but show little or no variation in response to inflammation. In the second part of the project, we will validate our findings by developing assays (likely immunoassays) for the molecules of interest and test them against a bank of human plasma samples taken from individuals whose iron status has been well characterised using conventional tests. If time persists, we will optimise the assay for the most promising molecule with a view to developing a low cost point of care assay for iron status that requires only very small volumes of blood.
Techniques to be used in this project include animal handling and phenotypic analysis, proteomics, possibly metabolomics, immunoassay development, and a range of conventional biochemical and molecular biology procedures.