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Control of tissue growth and cancer by the Hippo pathway


Project Description

A new frontier in biomedical research will involve watching individual proteins work in real time, in living organs. Traditionally, researchers have drawn conclusions about gene function using indirect techniques that only allow us to infer what a gene normally does, without actually watching it work. For example, we create organisms that lack a particular gene and determine whether something goes wrong. If the loss of gene X causes organs to overgrow then we assume that gene X normally limits organ size. This has been an extraordinarily powerful approach for interrogating gene function but it cannot substitute the ability to watch gene products executing their function in real time, which allows determination of exactly when, where and how they work.

You will investigate the role Hippo tumour suppressor pathway in organ growth by watching, for the first time, its, in growing organs, in real time. This will provide novel insights into normal organ growth and pathogenic organ growth in diseases such as cancer.
You will observe Hippo pathway activity in real time in the following situations:
a) When organs are actively growing
b) When organs stop growing
c) In regions of organs that are subject to mechanical compression
d) Throughout the cell cycle.

You will be taught an array of techniques including ex vivo organ culture, live multi-photon microscopy, image analysis and Drosophila genetics.


The Harvey laboratory studies mechanisms that control organ size during development and how deregulation of these processes contributes to human cancer. More specifically we: investigate developmental organ size control in the vinegar fly Drosophila; characterise the function of the Hippo pathway in Drosophila; and investigate the role of the Hippo pathway in human cancer.

We utilise the model organism, Drosophila melanogaster (vinegar fly), mouse models and mammalian cell culture to discover and investigate genes involved in tissue growth and cancer. Our approach is to identify genes involved in cancerous-like growth in flies and then use human and mouse models to determine whether the human counterparts of these fly cancer genes have a role in human cancer. Approximately 70% of human disease genes are conserved in flies, making it an excellent model for these studies.
https://www.petermac.org/research/labs/kieran-harvey

Peter MacCallum Cancer Centre, Melbourne Australia
Peter MacCallum Cancer Centre is Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

Tapping into the depth and breadth of knowledge and experience offered by the ten partners of the Victorian Comprehensive Cancer Centre (VCCC) alliance, the University of Melbourne’s Comprehensive Cancer PhD Program provides a unique opportunity for multidisciplinary cancer-related PhD candidates to experience clinical and research activities across the alliance.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program


Funding Notes

All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.

For further information about the university application process, see:
View Website

For further information regarding scholarships (both local and international), see:
View Website
Closing dates for applications for scholarships to commence in 2019: Round 1 -31 October 2018; Round 2 - 28 Nov 2018; Round 3 - 20 Feb 2019.

References

Manning SA, Dent LG, Kondo S, Zhao ZW, Plachta N, Harvey KF (2018). Dynamic Fluctuations in Subcellular Localization of the Hippo Pathway Effector Yorkie In Vivo. Curr Biol. 28(10):1651-1660.
Poon CL, Mitchell KA, Kondo S, Cheng LY, Harvey KF (2016). The Hippo Pathway Regulates Neuroblasts and Brain Size in Drosophila melanogaster. Curr Biol. 26(8):1034-42.
Harvey KF, Zhang X and Thomas DM (2013). The Hippo pathway and human cancer. Nat Rev Cancer. 13(4):246-57.
C. Poon et al., (2012) Current Biology. 17, 1587-1594.
Poon CLC, Lin JI, Zhang X and Harvey KF (2011). The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev Cell. 21(5):896-906.

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