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MASSIVE Research Stories: Australia’s Most Powerful Biological Microscope

Life and health ultimately depend on the interactions of large biological molecules – proteins, lipids, carbohydrates and others. How those interactions are initiated and proceed depends on the 3D shapes and structures of the participating molecules.

In February 2015, Monash University unveiled the most powerful biological microscope in Australia. The microscope is capable of providing detailed images of molecular interactions. The $5 million FEI Titan Krios cryo-Electron Microscope (cryo-EM) will transform the way we view the human immune system, and enable Australian researchers to work towards better treatment for diseases of the immune system, which include cancer, malaria, diabetes, rheumatism and multiple sclerosis.

But the capacity of the new microscope to do its job, which is to provide extremely detailed images, is heavily dependent on how the associated huge amounts of data are processed, stored and analysed. The accurate, reliable handling of all the data hinges on MASSIVE and its integration with the new machine.


The $5 million FEI Titan Krios cryo-electron microscope will transform the way we view the human immune system, and enable Australian researchers to work towards better treatment for diseases of the immune system, which include cancer, malaria, diabetes, rheumatism and multiple sclerosis.


 

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The inner workings of the FEI Krios electron microscope at the Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy that is being launched in early 2015. Image: Philip Chan.

 

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A fluorescence image of Drosophila (fruit fly) fat body. Researchers in the ARC Centre of Excellence for Advanced Molecular Imaging (Imaging CoE) are using drosophila models to discover new roles for perforin-like immune effectors in developmental and neuro-biology.

 

Along with the staff of MASSIVE, key players in this partnership will include A/Prof Hans Elmlund, director of the Clive and Vera Ramaciotti Centre for Structural Cryo Electron Microscopy, of which the Titan Krios is the centrepiece, and his wife A/Prof Dominika Elmlund. Both are members of the University’s Department of Biochemistry and Molecular Biology and associate investigators of the Imaging CoE.

Dominika and Hans met while studying for their PhDs at the Royal Institute of Technology in Stockholm. They both undertook post-doctoral fellowships in the laboratory of Nobel Laureate Roger Kornberg at Stanford University in California where they developed their research expertise around cryo-EM technology – Hans on the computing side and Dominika in structural biology and the preparation of samples.

“Getting this data processing pipeline up requires new algorithms which take full advantage of MASSIVE”, Hans said. “We need to develop a lot of new code.”

Those algorithms will also be fine-tuned for each experiment. For instance, different kinds of data need to be collected to construct images of large, inflexible sub-cellular bodies such as ribosomes, as opposed to small highly flexible structures such as membrane receptors.

The relationship between the cryo-EM and MASSIVE extends to providing temporary increases in computing power to handle data-processing for specific jobs, and determining and arranging the storage needed to archive the enormous amount of data the cryo-EM produces.

“We are talking about petabytes of data – thousands of terabytes,” Dominika explained.

And to support its community of cryo-EM users, most of whom are life scientists rather than computer experts, MASSIVE has “the most fancy remote desktop environment we’ve ever seen” according to the Elmlunds.

The major goal of the partnership between MASSIVE and the cryo-EM is to make the data-processing step easier and more efficient. That should result in users receiving their results – three-dimensional images of biomolecules – much more quickly, making them more competitive in the publication stakes. The aim is to decrease processing time from months to days.

MASSIVE is working with the Ramaciotti Centre to make processing and interpreting cryo-EM data as easy as possible. In future, when a researcher leaves the cryo-EM facility after capturing an image, the data should already be streaming to MASSIVE for processing, so that by the time they get back to their office, they are already in a position to start the first set of processing routines.


The major goal of the partnership between MASSIVE and the cryo-EM is to make the data-processing step easier and more efficient. That should result in users receiving their results – three-dimensional images of biomolecules – much more quickly, making them more competitive in the publication stakes.


 

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