Angus Kirkland is Science Director of the Rosalind Franklin Institute’s Correlated Imaging theme, with Judy Kim heading technological delivery as Deputy Director. For the talented researchers this opportunity is much more than two prestigious new posts, it represents the pinnacle of their successful 10-year scientific partnership.
With a background in materials science, Judy first met electron microscopy expert Angus when she moved to the University of Oxford as a post-doc. There, the pair managed the JEOL 2200MCO, a high-end microscope capable of routine sub-Ångstrom resolution.
Angus Kirkland and Judy Kim
After that, they designed and built two far more powerful electron microscopes within the Electron Physical Sciences Imaging Centre (ePSIC) at Diamond Light Source. But then the chance to do more presented itself when The Franklin came calling.
“It’s quite difficult in the UK and Europe to get significant capital investment to do really long-range disruptive developments,” says Angus. “I’ve been involved with The Franklin from its initial inception way back when because it was set up to do exactly that – disruptive science.”
Within the Correlated Imaging theme, Angus and Judy will use their previous experience to deliver on The Franklin’s core disruptive philosophy. “Now that The Franklin is coming online, we’re doing a very similar thing to what we did at ePSIC,” says Judy. “Except The Franklin instruments will actually be much more out of the ordinary.”
The ‘out-of-the-ordinary’ instruments Judy refers to are the world’s first pulsed cryo-electron microscopes. Angus explains: “We can record images at about a thousand frames per second already, but the target is to record images at a million frames per second at close to atomic resolution,” he says. “The big win will be to make molecular movies with proteins, or cells or cellular components actually in their native state in a liquid environment.”
Aiming to hit the ground running when the hub building is complete, Angus and Judy are already working with a Japanese industrial collaborator on the design and manufacture of the cryo-electron microscopes. But it is once the team and new instruments are settled in the building that the real work starts.
Amalgamating imaging data
The pair plan to correlate, or merge, data from the cryo-electron microscopes with different instruments that detect different signals over different spatial and time scales. This will be no mean feat – though progress has already been made in correlating light and electron microscopy, researchers have found it much more difficult to add other imaging instruments.
Bringing these disparate data together in a useful and informative way is “the big, big challenge” for the Correlated Imaging theme, but Angus and Judy are confident of success, and excited by the possibilities this capability would enable.
For Judy, the benefits of building a complete picture of a target – from the centimetre scale, which could be a tumour, all the way down to the picometre scale, which could be the individual atoms within a molecular structure – are important in a practical sense. “Today, your specimen often starts big and then you cut smaller and smaller pieces out to view at ever smaller scales,” she says. This can completely damage the specimen – something the correlated imaging techniques developed within the theme will circumvent.
Meanwhile, Angus is most excited by the multidisciplinary applications of their work. He says that correlating more and better imaging data could have a huge impact in future medicine. For example, tumour diagnosis would be far more accurate and detailed if it went from the tissue and cellular level, all the way down to the protein and atomic level.
It could also be crucial in drug discovery and our understanding of biochemical and biological processes. “People are always studying membrane proteins and how drugs can affect them for a host of diseases,” says Angus. These proteins undergo reversible structural changes when performing their biological function. To study membrane proteins, researchers have to freeze them in a certain state, which is highly challenging. “Instead, we could potentially analyse these membrane proteins live, which would be more reliable and informative.”