Hackett, Kristin

Project title: Mechanisms of proliferation in transformed immune and neuronal cells: The biological effects of iron deficiency and excess

Department: Biology

Faculty supervisor: Dr. Patrick Walter

"Iron is an essential element for normal biological function. However, it accumulates in highly proliferative cancer cells and when removed, cells cease proliferation and enter apoptosis. Although excess iron and iron deficiency have been extensively studied for their role in toxicity and tissue injury, little is known about the mechanisms by which iron influences cellular proliferation. We propose to investigate the effects of iron concentration on cellular proliferation by studying the cellular changes that occur in two different cell lines – immune and neuronal cells. These cell lines could give us insight into the different roles of iron in cancer and Parkinson’s Disease. The first goal is to quantify the transcriptional levels of the enzyme ribonucleotide reductase (RNR), an iron-containing enzyme that is essential to DNA synthesis, and deoxycytodine triphosphate (dCTP) concentrations in both cell lines. dCTP is one of the nucleosides synthesized by RNR and is particularly sensitive to changes in RNR activity. We hypothesize that with increasing iron there will be increased transcriptional levels of RNR as well as increased pools of dCTP and removing iron will inhibit these effects in both immune and neuronal cells. qPCR will be used to measure mRNA transcripts of RNR and a fluorescence-based qPCR assay will be done to quantify dCTP pool levels in both cell types. Through this we explore how iron concentration plays a role in cellular proliferation in these different cell types, thereby improving our understanding of iron’s role in cancer and Parkinson’s Disease."