Finding cures for children's genetic diseases

Telomerase structure

In collaboration with Dr Scott Cohen at CMRI and Professor Michael Parker at St. Vincent’s Institute (Melbourne), we aim to determine the atomic-resolution 3-D structure of the telomerase enzyme complex. An atomic-level structure will provide a template for rational and custom-designed small-molecule inhibitors of telomerase as potential anti-cancer therapeutics. The primary method for atomic-level structure is X-ray crystallography. Despite the progress we have made with our over-expression system, we are as yet unable to generate the milligram quantities of enzyme necessary for crystallisation trials. Thus, the over-expression system remains an active area of research.

Electron microscopy (EM) offers another method for obtaining structural information, albeit at lower resolution than X-ray crystallography can provide. In collaboration with Professor Ben Hankamer at the University of Queensland (Brisbane) we have recently obtained preliminary negative-stain EM images of purified human telomerase and are working towards the technique of cryo-EM using vitrified solutions to achieve higher resolution.