Using Nobel techniques to watch biomolecules at work

One of the first images taken with UNSW's new Zeiss Elyra 3D superresolution microscope (Jeremie Rossy)

Prof Katharina (Kat) Gaus, deputy director of the Australian Research Council’s Centre of Excellence for Advanced Molecular Imaging and head of its University of New South Wales (UNSW) node, is at the forefront of developing and applying the super-resolution fluorescence microscopy techniques that are the focus of this year’s Nobel Prize in Chemistry. She is using it to unravel at a molecular level how the body’s immune T cells make decisions which ultimately affect our health and well-being.

Kat was an early adopter of the technology. “The first papers on super-resolution fluorescence microscopy came out in 2006. It was so obviously a game changer for my medical research, that I was already using the technology by 2008. We published our first paper on it in 2011.”

Of the three Nobel laureates, she has met and talked to two—Stefan Hell and Eric Betzig. “One of my post docs will be visiting Eric for a couple of weeks early next year. He will take some of our samples to put under their microscope and pick Eric’s brains about them.”

Because super-resolution fluorescence microscopy is an optical technique based on light, it allows Kat to observe the interactions of individual molecules inside living cells over time, unlike techniques such as electron microscopy which result in the death of the cell.

Traditionally light microscopy is unable to distinguish two objects at distances of less than about half the wavelength of light apart—that’s 250 nanometres (millionths of a millimetre), much bigger that the size of an individual molecule. Super-resolution works around this barrier by attaching fluorescent tags to individual molecules that can be switched on and off. By taking a series of about 20,000 images of the same cell, and resolving it into one, a picture of the cell can be constructed molecule by molecule.

Kat has been collaborating with the renowned German manufacturer of optical systems, Carl Zeiss AG in developing the technology for her work. With assistance from EMBL Australia, she has established a Centre for Single Molecule Science in the Faculty of Medicine at UNSW.

“When the technology first came out, it was at the proof-of-concept stage. We have been working on it and turning it into a quantitative tool for science.” For instance, initially it took a long time to gather the information for an image, so they have improved its speed, and have also been working on generating precise 3D images, instead of the original 2D ones. “One of the overarching philosophies of the Imaging CoE is that technology development and research go hand in hand.”

Her new Centre for Single Molecule Science also has two Leica stimulated emission depletion (STED) microscopes, which build up images like a television, by scanning. “It’s much faster and helps to confirm what we have already found using the single molecule technique. We have just used it in an analysis of how molecules move inside cells.”

The technology is now beginning to spread more widely throughout Australia, and Kat’s team at UNSW are busy sharing their experience with others. “We have already hosted about half a dozen visitors, to help them with their research and allow them to test the technology before they buy it.”

Date Published: 
Monday, 13 October 2014