Snooping on the interplay of molecules

Centenary’s Cytometry, Imaging and IT Manager, Dr Adrian Smith

What can you discover with the latest Leica ground state depletion super-resolution microscope at between 40 and 60 millionths of a millimetre? Structures inside cells right down to the level of large molecules, such as proteins.

Given that much of the work of Centenary researchers is involved with studying protein interactions, there is already a lively queue forming to use the new Leica microscope, the first in the Southern Hemisphere. It has been acquired in collaboration with Sydney University’s Faculty of Science, the Sydney Medical School, the School of Medical Sciences, Bosch Institute, the Australian Centre for Microscopy and Microanalysis (ACMM) and Leica Microsystems itself.

Professor Jennifer Gamble, for instance, wants to study the movements and molecular interplay of the protein product of the gene SENEX which is associated with vascular disease and ageing. Professor John Rasko is interested in unravelling the interactions of a protein involved with diabetes and cancer. Dr Bernadette Saunders wants to get closer to the action between TB bacteria and their host cells. Professor Barbara Fazekas de St Groth is hoping to look at the molecular workings of the immune system, and Associate Professor Mark Gorrell wants to find in which cellular sub-compartments particular enzymes hang out.

The microscope is officially the first piece of equipment of the new Cellular Imaging Facility (CIF) in the multidisciplinary Charles Perkins Centre for the study of obesity, diabetes and cardiovascular disease. But until the Centre’s building is completed next year, it will be housed in the ACMM. It epitomises and cements the collaborative spirit of the Charles Perkins Centre and the CIF, says Centenary’s Cytometry, Imaging and IT Manager, Dr Adrian Smith, who expects the super-resolution microscope to become a core resource for the University and the wider Sydney research community.

Not only has the microscope been purchased with funds from several University of Sydney institutions, he says, but they and the Charles Perkins Centre, have decided to support the cost of its operation for the first year. This means researchers can use the super-resolution microscope without charge. The idea is to encourage people to train on it, get to know its capabilities and include the cost of using it in future research funding applications.

The majority of microscopes used for studying cellular structures depend on detecting the light of fluorescent tags attached to key molecules. The problem is that below a certain level of resolution the light from one molecule blurs into the next and the two cannot be resolved. The new super-resolution molecule uses high intensity laser light to switch off most of the fluorescent tags so that only a few molecules are flashing at a time. These can be located and their position stored on computer, which then gradually builds up an image of where the molecules are located.

Needless to say, the queue for the new Leica microscope is growing fast.