When David James did his PhD at the Garvan Institute in Sydney sometime back in the last millennium, he was one of only two postgraduate students and the institute was part of St Vincent's hospital laboratories.

In 2001, and after establishing himself as an internationally respected leader in diabetes and cell biology research, James returned to the Garvan to head its diabetes and obesity research program, in a newly fitted-out and vibrant research community comprising around 400 scientists and over 70 PhD students.

There are now about 70 people at the Garvan working on type 2 diabetes, which happens to be one James' long term interests. According to James, one important element about the program he heads is that it comprises independent groups each working on a different aspect of diabetes research. In addition, the program spans the whole breadth of focus, from basic science right through to clinical research using the latest technologies.

The program encompasses three different methodologies. Firstly, the researchers are trying to understand how insulin works under normal circumstances, because, as James puts it, "to figure out how the thing gets broken in disease, you have to know how it works normally". About two years ago, James came to the realisation that clinical science did not know as much about insulin action as was thought.

"I think a lot of people figured that insulin action was just about solved - insulin controls glycogen synthesis, glucose uptake, lipid synthesis and so on, and we just needed to understand those processes," he says.

James' group therefore decided to take a different and broader look at the issue. They focused on protein phosphorylation because most of the actions of insulin seem to involve this mechanism at some level.

Using stable isotope labelling and quantitative mass spectrometry, they screened different samples and cell populations to find novel phosphorylation events that occurred in response to insulin.

"We sequenced the phosphopeptides that came out of the screen (quite a list) and much to our surprise, found three to four that really captured our attention. These proteins provided a glimpse into what is clearly a much broader array of insulin actions than we thought." This work is soon to be submitted for publication.

At the Hunter Cellular Biology meeting, being held in the Hunter Valley this week, James will talk about two of these proteins that undergo substantially increased phosphorylation in response to insulin, neither of which were previously linked to growth factors.

Both proteins seem to play an important role in RNA stability, and particularly in microRNA (miRNA) processing. Such a role offers a whole new level of regulation of the insulin response, at the level of gene expression and translation. Growth factors such as insulin could regulate either the levels of message (mRNA) or the accessibility of message to the translational machinery in a very acute way.

"It is also possible that insulin signalling itself regulates miRNA processing, which is really interesting and exciting for us," James says. "We now want to figure out the nuts and bolts of this - what messages are being turned on and off by this pathway? That is going to probably take us into miRNA metabolism and other such areas that are a bit scary for a cell biologist."

More exciting results on one of these insulin-responsive phophoproteins have also come from a knockout mouse tracked down from a German thesis by one of James's PhD students. Testing by his group revealed these animals to have profoundly decreased muscle and adipose tissue mass compared to controls.

"This is very exciting because it suggests that insulin might regulate the differentiation or growth of these cells in a manner that is somehow dependent on miRNA processing or something like that- we don't really know yet. The results with this mouse might also take us down other avenues vis-a-vis the disease."