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Exploring the biological consequences of PIK3CA mutation in colorectal cancer


Project Description

Oncogenic activation of the phosphoinositide 3-kinase (PI3K) pathway is a common event in colorectal cancer (CRC). Indeed PIK3CA, the gene encoding the p110α catalytic subunit of PI3K, is mutated in approximately 20% of sporadic CRCs. Loss of function of the tumour suppressor APC (adenomatous polyposis coli) occurs in >80% of human CRCs and predisposes to benign intestinal adenomas mice.
We have recently established that Pik3ca mutation alone is insufficient to initiate intestinal tumourigenesis in mice but, in the context of Apc loss, Pik3ca mutation promotes the development of highly aggressive and invasive intestinal adenocarcinomas in vivo.

The student will use our novel mouse model of gastrointestinal cancer [1] to investigate the molecular mechanisms by which oncogenic mutation of Pik3ca and loss of Apc cooperate to cause accelerated progression of intestinal tumours and to identify novel routes for therapeutic intervention. This project incorporates a variety of functional assays and cellular and molecular biological techniques, including immunohistochemistry, microscopy, and in vitro organoid cultures.
This project could lead to the identification of novel biomarkers and/or new therapeutic approaches for CRC patients.

Research in the Phillips laboratory is focused on gastrointestinal cancers and has two major themes: Barrett’s oesophagus/oesophageal cancer and phosphoinositide 3-kinase (PI3K) mutations. These themes are unified by the use of in vitro and in vivo models to address key issues in the biology and treatment of cancer and are supported by a broad skill base in cellular, molecular and translational biology.

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:
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For further information regarding scholarships (both local and international), see:
View Website
Closing dates for applications for scholarships to commence in 2017: Round 1 -31 October 2016; Round 2 - 18 Dec 2016.

References

[1] Hare et al, Biochem J. 2014; 458(2):251-8. [PMID: 24320611].

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