Cancer Research Unit

Lab head: Hilda Pickett
Location: Children's Medical Research Institute

Telomere maintenance mechanisms in cancer

Primary supervisor: Hilda Pickett

Telomeres are specialised nucleoprotein structures at the ends of chromosomes, consisting of repetitive DNA (TTAGGG in humans) and associated proteins, which have a protective role and are necessary to maintain chromosome integrity and function.  Telomeres can exist in a stable secondary structure called a telomere-loop (t-loop), which is formed by strand invasion of the 3´ overhang into internal telomeric repeats on the same chromosome end.  Telomere length ultimately dictates how many times a cell can divide and is regulated by (i) gradual telomere attrition during cell division, (ii) rapid telomere deletion events in response to overlengthening known as telomere trimming, and (iii) activation of a telomere maintenance mechanism.

Telomere trimming was identified and characterised in the Cancer Research Unit at CMRI.  Telomere trimming involves resolution of the t-loop structure, and results in a shortened telomere and an extrachromosomal t-circle by-product.  This mechanism has been demonstrated to involve the recombination protein XRCC3.  The aim of this project is to induce rapid telomere deletion by the molecular manipulation of telomere trimming, and will involve a variety of molecular biology techniques including cloning techniques, transfection, protein localisation, telomere length analysis, tissue culture, and microscopy.  The overall goal is to limit cell proliferation in cancer cells by rapid telomere shortening.

Discipline: Pathology
Co-supervisors: Roger Reddel
Keywords: Telomere, Telomerase, Cancer