Iron Metabolism & Chelation Program - Honours projects available in 2009

An Honours project undertaken in this lab would be administered by the Discipline of Pathology.

The Iron Metabolism and Chelation Program is interested in examining the molecular and cellular mechanisms of the metabolism of iron in cancer cells. Iron is critical for the growth of neoplastic cells since it is required for DNA synthesis and cell cycle progression. Our laboratory has discovered novel drugs that act to inhibit the growth of cancer cells and further studies are critical to enable these drugs to enter clinical trials.

We have also discovered new metabolic pathways that are integral to tumour growth that rely on iron. In particular, a novel metastasis suppressor gene called N-myc downstream regulated gene-1 (Ndrg-1) has been found to be increased by our drugs and this may be important for inhibiting the growth of cancer cells.

A number of other projects are also available assessing the molecular mechanisms involved in the metabolism of iron in a variety of disease states, including iron overload disease and the devastating neurodegenerative disease, Friedreich's ataxia. We have developed exciting new drugs to treat this latter condition and have knockout mouse models to test the efficacy of our novel therapeutic strategies.

The Iron Metabolism and Chelation Program uses a very wide variety of techniques which span physiology, biochemistry, chemistry, cell biology, molecular biology and pharmacology.

This year we have 1 Honours student (Tom Pritchard) in our program and he is available for discussions regarding our laboratory and the work which we perform (tprichar@med.usyd.edu.au)

Our group use cell biology, molecular biology (PCR, Western analysis, in situ hybridization, radioisotope trace labeling, RT PCR, microarray analysis, proteomics etc), animal studies, X-ray crystallography, synthetic chemistry etc

Recent interesting publications

Richardson, D.R. (2004) Mysteries of the transferrin-transferrin receptor interaction uncovered. Cell 116(4):483-485.

Le, N.T.V. and Richardson, D.R. (2004) Iron chelators with high anti-proliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: A novel link between iron metabolism and proliferation. Blood 104(9):2967-75.

Richardson, D.R. (2005) 24p3 and its receptor: Dawn of a new iron age? Cell 123(7):1175-1177.

Watts, R.N., Hawkins, C., Ponka, P. and Richardson, D.R. (2006) Nitrogen monoxide (NO)-mediated iron mobilization from cells is linked to NO-induced glutathione efflux via MRP1. Proc. Natl. Acad. Sci. USA 103, 7670-7675.

Whitnall, M., Howard, J. Ponka, P. and Richardson, D.R. (2006) A class of iron chelators with a wide spectrum of potent anti-tumor activity that overcome resistance to chemotherapeutics. Proc. Natl. Acad. Sci. USA 103:14901-6. Blood. 110, 752-761.

Fu, D. and Richardson, D.R. (2007) Iron chelation and regulation of the cell cycle: Two mechanisms of post- transcriptional regulation of the universal cyclin-dependent kinase inhibitor p21^CIP1/WAF1 by iron-depletion. Blood. 110, 752-761.

Nurtjahja-Tjendraputra, E., Fu, D., Phang, J. and Richardson, D.R. (2007) Iron chelation regulates cyclin D1 expression via the proteasome: A link to iron-deficiency mediated growth suppression. Blood. 109:4045-4054.

Whitnall, M., Suryo Rahmanto, Y., Sutak, R., Xu, X., Mikhael, M., Ponka, P. and Richardson, D.R. (2008) The MCK mouse heart model of Friedreich's ataxia: Marked alterations in iron-regulated proteins and iron chelation limits cardiac hypertrophy. Proc. Natl. Acad. Sci. USA (In Press).

1. Development of new iron chelators as novel drugs against cancer

Supervisor + contact details:

• Professor Des Richardson
• Dr David Lovejoy

This project will use a combination of techniques that are implemented in chemistry, biochemistry, physiology, molecular biology and pharmacology to design and assess the activity of novel drugs for the treatment of cancer. Your project will be multi-faceted and will involve growing human tumour cells in tissue culture and assessing the effects of chelators on gene expression. This will be done using Western analysis, RT-PCR and microarray analysis. The lab has considerable experience in these cutting-edge techniques and you will be taught the intricacies of their use.

Feel free to contact Prof. Des Richardson or Dr. David Lovejoy (dlovejoy@med.usyd.edu.au) to have a chat about whether the project matches your interests.

2. Transport of nitric oxide in cells and its interaction with iron containing proteins in tumour cells

Supervisor + contact details:

• Professor Des Richardson

This project will use a combination of techniques that are used in biochemistry, physiology, cell biology, molecular biology and pharmacology. Your project will be multi-faceted and will involve growing human tumour cells in tissue culture and assessing the effects of nitric oxide on the iron transport. This will be done using a wide variety of techniques including Western analysis, RT-PCR and microarray analysis. The lab has considerable experience in these cutting-edge techniques and you will be taught the intricacies of their use.

Feel free to contact Prof. Des Richardson to have a chat about whether the project matches your interests.

3. The function of the malignant melanoma tumour antigen, melanotransferrin (p97), in tumourigenesis

Supervisor + contact details:

• Professor Des Richardson

This project will use a combination of techniques that are used in biochemistry, physiology and molecular biology. Your project will be multi-faceted and will involve growing human tumour cells in tissue culture and the use of a number of knockout and transgenic mouse models developed in our laboratory. A wide variety of techniques will be used including Western analysis, RT-PCR and microarray analysis. The lab has considerable experience in these cutting-edge techniques and you will be taught the intricacies of their use.

Feel free to contact Prof. Des Richardson or Mr. Yohan Rahmanto (yohans@med.usyd.edu.au) to have a chat about whether the project matches your interests

4. The role of iron in the pathogenesis of the crippling neurodegenerative disease, Friedreich's ataxia

Supervisor + contact details:

• Professor Des Richardson

This project will use a combination of techniques that are used in biochemistry, physiology, pharmacology and molecular biology. Your project will be multi-faceted and will involve growing cells in tissue culture and the use of a unique knockout mouse model. A wide variety of techniques will be used including Western analysis, RT-PCR and microarray analysis. The lab has considerable experience in these cutting-edge techniques and you will be taught the intricacies of their use.

Feel free to contact Prof. Des Richardson or Miss Megan Whitnall (meganw@med.usyd.edu.au) to have a chat about whether the project matches your interests.