Telomere Length Regulation Unit, Children's Medical Research Institute

Lab head: A/Prof. Hilda Pickett
Location: Children's Medical Research Institute, Westmead

Telomeres are structures at the ends of linear chromosomes that maintain chromosome integrity. The Telomere Length Regulation Unit investigates the intricate balance between telomere lengthening and shortening processes, which ultimately determines the proliferative capacity of a cell. Telomere length dysregulation can result in cancer, or in an emerging spectrum of premature aging disorders.

Funding: NHMRC, Cancer Council NSW
Research approach equipment: molecular biology advanced microscopy tissue culture cell biology biochemistry bioinformatics

A current list of A/Prof Pickett’s publications can be found on her Sydney Medical School profile page.

Using telomere length analysis to understand human disease

Primary supervisor: Hilda Pickett

Telomeres are specialised nucleoprotein structures at the ends of chromosomes, consisting of repetitive DNA (TTAGGG in humans), as well as associated proteins and RNA. Telomeres provide a protective role to the chromosome and are necessary for the maintenance of genome 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 maintenance is vital for the continued growth of tumour cells and occurs either by activation of the enzyme telomerase, or by recombination-mediated telomere replication referred to as alternative lengthening of telomeres (ALT). We are investigating how telomere maintenance mechanisms become activated in cancer cells, with the ultimate goal to develop novel treatment strategies that can be applied to all types of cancers. In addition, it is becoming increasingly clear that telomere length and underlying polymorphisms or mutations in genes involved in telomere maintenance can predispose an individual to a variety of diseases, and can be used to identify disease susceptibility. We are investigating how telomere length defects contribute to human aging and disease.

Our lab use a wide range of cellular and molecular biology techniques, tissue culture, microscopy and live cell imaging, proteomics, and bioinformatics. A committed student will have the opportunity to substantially advance this research field.

Discipline: Applied Medical Sciences, Westmead
Keywords: Telomere, Telomerase, Cancer