Exploration of the cellular iron regulatory network

Mingang Zhu

Genetic aberrations in iron metabolism genes and alterations in cellular and systemic iron availability induce compensatory mRNA expression changes within the iron regulatory network. Such expression changes can be monitored by microarray analysis and, presumably occur, to balance cellular iron levels or counteract the toxic side effects of iron overload or deficiency.
We recently applied a systematic siRNA knock-down strategy using RNAi-arrays and automated fluorescent microscopy to assess whether these differentially expressed genes affect transferrin receptor 1 (TfR) expression and transferrin uptake into cells.
This experimental approach identified a list of genes that are functionally linked to the iron regulatory network. Experiments are ongoing to further explore the link between iron metabolism and the identified candidate genes using cell based assay systems and mouse models.