Investigating MYB

Besides organising robotics platforms, Gonda's real work is in his primary research interests in leukaemia and breast cancer.

He will use the screening technology to investigate genes that might affect differentiation of haemopoietic cells and the growth of breast cancer, for instance. Gonda has long studied the MYB gene, which was originally discovered in chicken leukaemia viruses and has some very good, and very bad, functions.

"MYB is essential for haemopoiesis ... but it is expressed in a large proportion of breast cancers, in leukaemia, and in colon cancers as well," he says.

"The interesting thing about those diseases and about where MYB is probably functioning in normal situations is that all of those three systems - blood development, developing mammary glands and colon - are rapidly turning over cell systems.

You are constantly making blood cells, constantly making gut cells and during pregnancy and lactation the mammary cells are proliferating rapidly and differentiating.

"So you have this coupled process of rapid growth and differentiation in all three of those systems. That's what we believe MYB is involved in - somehow this coupling of rapid growth and differentiation."

One area of interesting research involving MYB is that it is turned on by oestrogen. Last year, Gonda and colleagues showed how the oestrogen receptor turns on MYB and that MYB is actually necessary for the proliferation of oestrogen-receptor positive breast cancer cells.

The new robotics platform at the Diamantina will help further this research, he says. "One of the things that we can do with this system is that if you set up appropriate reporter assays you can look for genes that modulate the activity of a reporter.

"So for example, one of the things that we want to do is to look for genes that can affect either the activity or the control of expression of MYB. If we use a cell line that has a reporter for MYB we can put all of these genes in and can either over-express them or actually knock them out and see which one can affect MYB.

"One of things where not much is known about MYB, one of the big questions, is how MYB is actually regulated. People knew that MYB is turned off and on in certain circumstances but no one knew what any of the signals were and that's something of great interest. At least in the breast cancer cells we identified the oestrogen receptors as being what's upstream of MYB and we figured out how it actually worked.

"MYB's got an interesting mode of regulation - it turns out that instead of being regulated by the transcription actually starting, what happens is that the promoter of MYB is on all of the time in most cells but it is blocked in the middle of the first intron of the gene.

"So if MYB is switched on that block is overcome and that's what oestrogen and oestrogen receptors seem to be doing. We are interested in the signals that regulate MYB in maybe other cell types where it is turned on and off, say in blood cells or colon."