Fat and Expanded

At the Hunter meeting, Harvey will also discuss new findings on the temporal control of SWH pathway activity throughout Drosophila development.

"To date, all pathway components were thought to function throughout development in flies. However, we have found that although the four core components of the pathway act early on to regulate growth and proliferation and later on in development to drive apoptosis, other upstream components act differentially.

"In particular, Fat and Expanded appear to control organ size during the growth phase, but play no role in triggering apoptosis once the organ reaches critical size."

Harvey's group has also started to look at the role of SWH pathway components in different human cancers, and several members have been implicated already. According to his recent article in Nature Reviews Cancer (Harvey and Tapon, 2007), "evidence from patient samples, cancer cell lines and mouse models indicate that disruption of the analogous human pathway is involved in tumorigenesis".

At the Peter MacCallum Cancer Centre, Harvey has access to a large array of tumour samples from patients across the cancer spectrum. Using this resource, his team will search for mutations in individual pathway genes, as well as staining tumours for expression of transcriptional enhancer protein, YAP, which is the mammalian orthologue of the fly protein yorkie.

"Essentially, instead of going in and sequencing all known pathway components in each sample, we are looking for expression of this common key downstream protein," Harvey says. "All of the upstream components of the pathway impinge on this one oncoprotein and regulate its stability, phosphorylation and shuttling between nucleus and cytoplasm."

Once his team has found a class of tumours with increased YAP expression, they will sequence the tumour suppressor genes involved and do functional assays.

Career development

Kieran Harvey received funding from the Human Frontier Science Program (HFSP) in 2006 to set up his laboratory in Australia. HFSP is a prestigious international granting body that has Australian membership through the National Health and Medical Research Council (NHMRC), involving more than $70 million in grants and fellowships each year.

Harvey also won a Career Development Award from the Leukemia Lymphoma Society and a Peter MacCallum Cancer Centre Junior Investigator Award to help kick-start his independent research career back in Australia.

As testament to those funding decisions, Harvey has continued to make pivotal findings in the field of development cell biology, and last year secured a four-year Australia Career Development Award Fellowship from the NHMRC.