Professor Julian Mercer
Position: Head, Centre for Cell & Molecular Biology
Affiliation: School of Biological & Chemical Sciences, Deakin University
Phone: +61 (03) 9251 7329
My research centres around the molecular analysis of the genetic defects of copper transport. My group has been investigating the genetic basis of the X-linked copper deficiency disorder, Menkes disease. In 1993 in collaboration with Dr Tom Gloverís group (Michigan), we reported the isolation of the gene by positional cloning [Nature Genetics 3: 20-25, 1993]. This breakthrough has opened the way to analysis of the gene structure [Genomics 28: 462-469 (1995)], and investigation of mutations in the mouse models of this disease [Nature Genetics 6: 374-378 (1994)]. In collaboration with Dr Jim Camakarisís group (University of Melbourne) we discovered that the cells become copper resistant by amplification of the Menkes gene due to an enhanced ability to efflux copper, the first clear evidence that the Menkes protein (MNK or ATP7A) is involved in pumping copper out of the cell. Current research involves investigation of the mechanism by which copper affects the intracellular location of the Menkes protein. When cells are exposed to copper the protein relocalises to the plasma membrane thus enabling the efflux of this potentially toxic metal ion. Thus our research is moving into the cell biological mechanisms related to the regulation of protein trafficking, the effect of mutations on this process and the relationship between mutations and disease phenotypes.
We are also investigating the closely related protein which is affected in the genetic copper toxicosis condition, Wilson disease. We are primarily studying a mouse model of this condition, the toxic milk mouse. We have determined the mutation in the mouse homologue of the protein product of the Wilson gene, WND (or ATP7B)and have engineered this mutation in a cDNA construct to study the effect of the mutation on the activity of WND. We are currently using cultured hepatoma cells to investigate the trafficking of WND in a polarized cell. The toxic milk mouse is being used to develop more effective strategies for treatment of Wilson disease, including possible gene therapy, in collaboration with the Gene Therapy unit at the Murdoch Institute (Royal Childrenís Hospital).
Prof Marc Solioz, Berne, Switzerland