Dr Kieran Harvey from the Laboratory of Cell Growth and Proliferation at the PeterMac Centre in Melbourne is interested in how organ growth and size are regulated during development by the newly discovered Salvador-Warts-Hippo (SWH) signalling pathway. Activation of this pathway restricts organ size by limiting cell growth and proliferation and by stimulating cell death via apoptosis.

Harvey's primary interest is how this system works in Drosophila melanogaster, where the pathway was identified, but the work also has important implications for human tumorigenesis as control of proliferation and cell survival are also central to the development of cancer.

At the Hunter Cell Biology meeting this week, Harvey will present his group's latest findings on this important signalling cascade in fruit flies and how this might translate to human disease.

Harvey's interest in the pathway with the eclectic name is more than academic - he was part of its discovery. After completing a PhD in cell biology with Sharad Kumar at the University of Adelaide in 2000, Harvey took up a five-year postdoctoral position at the Massachusetts General Hospital Cancer Center in Boston and the University of California, Berkeley. In the laboratory of developmental cell biologist Iswar Hariharan, Harvey started working with Drosophila as a model organism for the first time.

"We were screening flies for genes that gave cells a growth advantage, looking for outgrowth of tissues such as eyes and wings," Harvey says. The group identified two components of a previously undiscovered pathway - a novel gene called Salvador, and a previously known gene called Warts (published in Cell, 2002).

They subsequently found Hippo and Yorkie, and together, these four genes comprise the core components of the Drosophila SWH pathway, required for normal cell growth, proliferation and apoptosis.

Identifying Hippo and showing that it controlled tissue growth with Salvador and Warts comprised a second Cell paper for Harvey in 2003. Deregulation of the SWH pathway causes a significant and abnormal increase in organ size, which is lethal for developing flies and clearly of more general biological significance.

Twelve components of the SWH pathway have now been identified in flies, mostly using clonal screens for genes that affect organ size. All of these have mammalian counterparts and several have been implicated as tumour suppressors or oncogenes.

According to Harvey, many of these were known genes, discovered in the 1980s and 90s by different groups and later slotted into the SWH pathway. The components belong to a range of protein classes: kinases (Hippo and Warts and Discs overgrown), scaffold molecules (Salvador), membrane-associated signalling proteins (Expanded and Merlin), and cytoskeletal motors (Dachs) to transcriptional regulators (Yorkie).