Contact Dr Heloisa Zaccaron Milioli about research supervision opportunities: h.milioli@garvan.org.au 

Project 1 - Cancer Cell Translatome: The Machinery Fuelling Chemotherapy Resistance

Chemotherapy resistance remains one of the most significant unresolved challenges in oncology. Although many cancers initially respond to treatment, a subset of cells can survive by activating stress-adaptation programs. These resilient cells often acquire more aggressive behaviours and ultimately drive disease progression, metastasis and relapse. Preventing stress-adapting programs is likely to lead to therapeutic strategies to prevent the emergence of chemotherapy-resistant disease

Our laboratory is positioned to uncover the non-genetic mechanisms that enable cancer cells to adapt and survive under therapeutic pressure. In particular, we focus on the largely underexplored cancer cell translatome – the machinery that determines how mRNAs are translated into proteins. Compared to genetic changes, translational regulation is rapid, dynamic, and uniquely capable of rewiring the proteome, giving cancer cells a powerful survival advantage during therapy exposure. By leveraging unique resistance models and state-of-the art technologies – including polysome profiling, Ribo/RNA-Seq, proteomics, and integrative bioinformatics – we are systematically mapping the translational rewiring events that drive therapy resistance.

This project aims to (1) define the mRNA translational programs that enable cancer cells to resist therapeutic stress, and (2) identify and validate targetable vulnerabilities of the cancer cell translatome to prevent or overcome therapy resistance, leading to more effective strategies to eradicate cancer.