February 1, 2015

A titanic electron microscope that snap-freezes cells to reveal immune secrets

Launch of the $20 million Clive and Vera Ramaciotti Centre for Structural Cryo Electron Microscopy

Monash University, Melbourne — 11am Monday 2 February 2015

With Prof Aidan Byrne, CEO of the Australian Research Council; Prof Edwina Cornish, Provost and Senior Vice-President, Monash University; and Caitriona Fay, National Manager Philanthropy, Perpetual.

A unique $5m electron microscope launched today at Monash University, Melbourne, will transform the way we view the human immune system, and advance Australian research towards better treatment for diseases from cancer and malaria to diabetes, rheumatism and multiple sclerosis.

The FEI Titan Krios cryo-electron microscope is the centrepiece of the $20 million Clive and Vera Ramaciotti Centre for Structural Cryo Electron Microscopy. Standing 3m tall, weighing around a tonne, and with a powerful 300kV electron gun, it’s a true giant of a machine.

The Ramaciotti Centre and its new microscope are central to the work of the ARC Centre of Excellence in Advanced Molecular Imaging, of which Monash University is a lead partner.

“We want to transform our understanding of the human immune system,” says James Whisstock, the director of the Imaging Centre. “To achieve this, we need to be able to observe the molecular structures at the heart of immune response. Our immune system, and thus our health, is ultimately driven by the interactions of these large biological molecules. And those interactions depend on the 3D shapes and structures of the molecules involved.”

“The Titan Krios is powerful enough to resolve those intricate 3D shapes, identifying the position of individual atoms within a biological molecule and creating exquisitely detailed models including the molecules’ loops and side chains, James says. “It fills a gap, seeing things that X-ray crystallography and the Synchrotron can’t see. And Australian scientists have been queuing up to get time on Titans in Europe and America. Now they can do the job in Australia.

Projects that will use the Titan include studies of:

  • a drug that can prevent the spread of the malaria, a disease that still infects hundreds of millions of people and causes more than 600,000 deaths a year—Dr Wilson Wong, Walter and Eliza Hall Institute of Medical Research (WEHI)
  • key molecules which help infective bacteria acquire resistance to front-line drugs—Prof Trevor Lithgow, Microbiology, Monash University
  • mitochondria, fundamental research into the energy powerhouses of all cells—Prof Michael Ryan, Monash University
  • insulin and its receptor, the key to diabetes—Assoc Prof Mike Lawrence, WEHI
  • perforins, molecules that form pores in membranes of infected cells, as a precursor to their elimination—Prof James Whisstock, Imaging CoE, Monash University
  • receptors that trigger the T cells of the immune system—Prof James McCluskey, The University of Melbourne and Prof Jamie Rossjohn, Imaging Centre, Monash University
  • transcription, the first step in the process by which genetic material is transcribed by giant enzymes called polymerases—A/Prof Hans Elmlund and A/Prof Dominika Elmlund, Imaging Centre, Monash University.

The new microscope facility has been funded with support from the Ramaciotti Foundations, the Australian Research Council (ARC), Monash University, the Walter and Eliza Hall Institute of Medical Research (WEHI), La Trobe University and the National Health and Medical Research Council of Australia.

How it works
The Titan Krios electron microscope fires a stream of high-energy electrons through a thin sample that’s frozen in a pool of liquid ethane at 200 °C below zero. Some of the electrons in the beam are deflected or absorbed by the molecules in the sample when they pass through it, and these deflected rays can be used to create a two-dimensional image of the sample. Multiple two-dimensional images obtained by passing the electron beam through many hundreds of samples can then be automatically pieced together to determine the three-dimensional shapes.

Use of an electron beam allows much greater magnification than in visible-light microscopes, and the Titan Krios can achieve magnification of several billion times, resolving the positions of individual atoms in an immune-system molecule.

Snap-freezing the cells allows researchers to look at immune molecules in a more natural state: as close as practical to living cells.

About the Imaging Centre
Understanding our immune system is central to fighting cancer, infectious diseases such as malaria, and auto-immune diseases such as diabetes, rheumatism and multiple sclerosis. The key to understanding and treating these diseases lies in understanding how proteins and cells interact at the molecular level.

The Imaging Centre aims to transform our understanding of the immune system, and in doing so transform the science of microscopy, and position Australia at the leading edge of that field.

The multidisciplinary Centre brings together physicists, chemists and biologists from five universities to characterise and visualise the key interactions that underpin immune responses. Centre researchers are based at La Trobe University, the University of Melbourne, Monash University, the University of New South Wales and the University of Queensland.

They’re supported by partners from the Australian Nuclear Science and Technology Organisation, The Australian Synchrotron, Carl Zeiss Pty Ltd, Deutsches Elektronen-Synchrotron (Germany), Leica Microsystems Pty Ltd and the University of Warwick (UK).

The opening of the Ramaciotti cryo-electron microscope facility at Monash University is the latest addition to a suite of equipment use by Imaging Centre researchers, from $2 smartphone microscope lenses, to the $200 million Australian Synchrotron and Europe’s new 3.4 km long, $1.25 billion X-ray free-electron laser.

About Ramaciotti
The Ramaciotti Foundations were established by siblings Vera and Clive Ramaciotti in 1970 with $6.7 million in funds, proceeds from the sale of the Theatre Royal in King Street, Sydney. In the four decades since their first major seeding donation to found a new research laboratory at the Walter and Eliza Hall Institute of Medical Research in 1971, Ramaciotti has donated close to $55 million to biomedical research. They are one of Australia’s largest private contributors in the field. The Ramaciotti Foundations are managed by Perpetual.

Backgrounders available on
Microscopy: the Imaging Centre is working with $2 microscopes—million dollar microscopes and ten-billion dollar microscopes; where does the Titan fit?
Monash infrastructure: from crystals to the Titan, to walking through molecules—the tools that underpin life science research.