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.

Understanding protein dephosphorylation in the DNA damage response

Primary supervisor: Hilda Pickett

By screening breast cancer samples, we have identified a novel protein phosphatase that regulates DNA repair pathway engagement at telomeres. We aim to investigate the role of this protein in the DNA damage response specifically at telomeres, with the overarching aim to understand how this protein contributes to genome stability and cancer development.

Genome integrity is constantly being challenged by DNA lesions that arise from endogenous and exogenous sources. If left unrepaired, DNA damage can cause mutations and chromosomal aberrations, which have catastrophic consequences. Therefore, cells have developed complex DNA damage signalling and repair pathways to counteract the adverse effects of DNA lesions. One of the most important properties of the DNA damage response (DDR) pathway is its ability to respond to DNA damage in a rapid and dynamic manner. Much of this is achieved by posttranslational modifications of DDR proteins, of which phosphorylation is the most prominent. Considerable advances have been made in identifying the key protein players and elucidating the intricacies of DDR factor assembly at DNA lesions. However, one of the major unanswered questions is how specific DNA repair pathways become engaged. We have identified a novel phosphatase involved in DNA repair and the maintenance of genomic stability. We aim use the natural ends of linear chromosomes (telomeres) to study the role this protein plays in DNA repair pathway choice, identify its molecular targets, and determine how expression of this protein contributes to DNA repair pathway choice.

Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Dr Alexander Sobinoff
Keywords: Cancer, Telomere, DNA damage