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Exploring emerging roles of p53 isoforms in epigenetic dysregulation in cancer

A postgraduate research opportunity at the University of Otago.

Details

Close date
Sunday, 31 January 2021
Academic background
Sciences, Health Sciences
Host campus
Dunedin
Qualifications
Honours, Master’s
Department
Pathology (Dunedin)
Supervisors
Dr Marina Kazantseva, Dr Tania Slatter

Overview

Silencing of tumour suppressor genes by a process called DNA methylation is thought to be an early and driving event in the tumourigenesis and is a hallmark of cancer, but how this epigenetic switch is triggered in cancer cells remains largely unknown. We have evidence that Δ133p53 - truncated oncogenic isoform of the p53 tumour suppressor plays central role in this process.

Preliminary data obtained in lung cancer cell lines engineered to expresses Δ133p53 isoforms showed Δ133p53 may contribute to inactivation of genes that protect us from cancer through DNA modification mechanisms. Here we propose to explore whether we can reactivate tumour suppressor genes silenced in Δ133p53-expressing lung cancer cells using cutting-edge chimeric deactivated CRISPR-dCas9-based technology. This will enable to confirm the functionality of epigenetic modifications induced by the isoform. As epigenetic changes are reversible, this may uncover attractive targets for cancer treatment.

Contact

Marina Kazantseva
Tel   +64 3 479 7169
Email   marina.kazantseva@otago.ac.nz