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Molecular vulnerabilities and biomarkers of telomere maintenance states for exploitation in cancer treatment

Summary

The goal of this project is to demonstrate the therapeutic potential of molecular targets associated with telomere biology of cancer cells.

Supervisor

A/Prof Karen MacKenzie.

Research location

Westmead - Childrens Medical Research Institute

Synopsis

Telomeres are structures at the ends of chromosomes that function to prevent chromosome instability. In normal cells telomeres are lost during cell division, which limits their overall replicative ability. However, in most cancers, telomere loss is overcome by activation of a telomere maintenance mechanism that provides cancer cells with unlimited ability to replicate (cellular immortality). Telomere maintenance mechanisms present an important mechanism for therapeutic targeting in immortal cancer cells.

Our group has a strong history of discoveries in telomere biology, including the discovery of the Alternative Lengthening of Telomere (ALT) mechanism in 1996 and the development methods relating to the detection of ALT that have been extensively applied by researchers across the world in studies of diverse cancer types. To provide a resource for exploiting telomere biology in the development of new cancer treatments, our group has recently completed a project that characterised telomere maintenance mechanisms in approximately 1000 cancer-derived cell lines, representing more than 30 different types of cancers. We are using this dataset, in conjunction with proteomic data and other ‘omic data sets, to identify cancer cell vulnerabilities, opportunities for drug repurposing and biomarkers associated with telomere biology. This student project will use this dataset as a platform to explore unusual telomere biology states in cancer cells and to experimentally validate candidate therapeutic targets related to telomere maintenance mechanisms.  This will involve application of a variety of cellular and molecular biology techniques to functionally demonstrate the impact of modulating the expression of proteins of interest in cancer cell lines and other model systems. The project will be conducted in an exceptional research environment, with support of supervisors with long-standing expertise in telomere biology. The outcomes will have potential for application in the development of new therapeutic approaches for precision medicine treatment of aggressive cancers. 

Additional information

The host laboratory is located at Children's Medical Research Institute (CMRI) at Westmead, a major hub for health and medical research associated with Sydney University.

Opportunities are available for PhD candidates to apply CMRI PhD Research Award. Visit the CMRI website for more information.

https://www.cmrijeansforgenes.org.au/research/opportunities-for-research-students/cmri-phd-research-award

https://www.cmrijeansforgenes.org.au/research/research-teams/cancer

https://www.cmrijeansforgenes.org.au/researchers/karen-mackenzie

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Opportunity ID

The opportunity ID for this research opportunity is 3020

Other opportunities with A/Prof Karen MacKenzie