Targeting cell death pathways in biliary tract cancers
- Research Opportunity
- Number of Honour Places Available
- Medicine and Radiology
- Austin Health
|Prof John Mariadasonemail@example.com||9496 3068||Personal web page|
|Dr Doug Fairlie|
Biliary tract cancers (BTC) are cancers which arise in the bile ducts, the vessels which drain bile produced in the liver for storage into the gallbladder and subsequent release into small intestine. There are a number of risk factors associated with the disease including chronic inflammation, as well as liver fluke infections. Most BTC patients present with advanced disease and the prognosis is generally poor with median survival of about 12 months. Chemotherapy is the standard treatment though this only has a modest effect on patient outcomes.One of the key hallmarks of most, if not all, cancers is defective apoptosis signalling. This is often due to over-expression of the pro-survival members of the Bcl-2 family of proteins. As a consequence, a new class of drugs ("BH3-mimetics") that directly target these proteins has been developed, and is showing significant promise for the treatment of certain cancers. However, there have been only very limited studies using these drugs in BTC.
This project will examine a large panel of BTC cell lines for their sensitivity to a range of BH3-mimetic drugs, both as single agents as well as in combination with each other. This will enable us to precisely dissect the critical survival "factors" in the tumours and establish whether those from distinct locations within the biliary tree behave similarly. As we have detailed genomic information from these cell lines, we can also design potential drug combinations with BH3-mimetics that might provide enhanced cell killing activity. The mechanism-of-action of BH3-mimetics in BTC will also be examined.Students undertaking this project will use a variety of techniques including cell culture, in vitro cell assays, CRISPR/Cas9 gene editing, FACS, Western blotting, immunohistochemistry as well as basic molecular biology techniques.
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Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research
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