Microscopy Blog - 12 July 2019 - What's so special about EM?

In the past week, the Bio21 Institute has received a cryo-electron microscope (EM) Glacios. The instrument belongs to the Monash Institute of Pharmaceutical Sciences (MIPS), but in exchange for housing the microscope we receive shared access to it.

Since the commissioning of the Talos Artica (200kV cryoTEM) and the Talos L120C (120 kV microscope) in 2019, we now have a good collection of CryoEM microscopes at Bio21 which will be further strengthened with the arrival of two other instruments mid-2020.

Globally, Australia has been a late-adopter of this new, but revolutionary technology that won Jacques Dubochet, Joachim Frank and Richard Henderson, the Nobel Prize in Chemistry 2017.
With considerable investment and also recruitment, we’re catching up and starting to see results from these remarkable instruments.

What is special about these instruments?

CryoEM allows you to peer into samples that have been ‘snap frozen’. For a layman’s analogy, it is like frozen peas: they have advantages over canned peas, retaining their look, freshness, vitamins and taste, while canned peas (fixed cells and proteins) have a slightly different look and very different taste.

We are now able to visualise protein structures in solution and in their native state, providing further insights into the behaviour and function of proteins and molecules in cells, particularly the interactions of drugs with drug targets.

When the new microscopes arrive next year, we will be able to do the same but in the context of the cellular environment. This technology complements the data we receive from mass spectrometry, magnetic resonance spectroscopy and X-ray crystallography, also housed in the Institute.

But with all the buzz and excitement around cryoEM, let us not forget the other electron microscope capabilities we house at Bio21.

Most of us look at electron microscopy as a two dimensional technique. But for the last 50 years the third dimension has always been there for us to use. Since its inception, Bio21 has had the capability to do tomography and even cryo-tomography, providing a very much-needed third dimension in applications such as, cell biology, nanomaterials and solar cells.

This is the equivalent of you receiving a CT-scan whereby the machine rotates around your injured limb. In the case of EM, it is the sample rotating in the microscope.

It produces a very high resolution, three dimensional (3D) structure, encompassing the whole sample size (which must remain within the limits of the lower microns and 300 nm in thickness).

In the last four years, with the purchase of an automated block-face imaging SEM and a new automated serial section ultra-microtome, we have expanded our capability in 3D imaging to reach volumes in the 1mm3 range, at resolutions closer to 10 nm. 

Hence, we are now able to conduct 3D imaging in a sample size range spanning from molecules (angstrom range resolution) through to tissues (nanometer range resolution).

The missing piece in the puzzle is the elemental composition of the sample of interest. For this we turn to ‘microanalysis’. We have five microscopes capable of visualizing each atomic element from Boron upwards (at a few nm resolution) in a tissue, in individual particles, or even in bulk samples. For lighter elements (B to Zn), we are one of the few facilities worldwide that can do this under cryogenic conditions.

All of these wonderful “toys” will be relocated mid-2020 in our new home-to-be, the Bio21 ‘Stage 2C’ building (Ex VRI, building 403), currently under construction.

So, whatever you are hoping to look at in your samples, please come and speak with me and the team in the Advanced Microscopy Facility, and we will endeavour to find the most effective method for your analysis.

ehanssen [at] unimelb.edu.au (Associate Professor, Eric Hanssen)
Advanced Microscopy Facility