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.