New multi-million-pound initiative between The Rosalind Franklin Institute and the LMB aims to develop a new detector to produce better data and make cryo-EM more accessible
Richard Henderson and Chris Russo from the LMB are working with The Rosalind Franklin Institute (The Franklin), and detector development specialists from UK Research and Innovation’s Science and Technology Facilities Council (STFC) to develop an improved detector for cryo-EM. The new detector will be able to work at 100 keV, versus the current industry standard 300 keV, to enable atomic scale images of biological samples.
More importantly, the new detector will produce better data from the lower energy, 100 keV microscope than existing detectors working with higher energy microscopes. Detectors that are optimised for 300 keV electrons can be used at 100 keV but they are expensive and are limited by their small pixel size which can be computationally increased, but this reduces the field of view and increases complexity.
The development of this new detector builds upon earlier proof-of-principle work at the MRC LMB. Here, Chris’ group, with help from the scientific workshop, built a prototype of a 100 keV microscope that resolved five structures in seven days, but it was clear that an optimised detector was essential to fully realise the potential of the new microscope design.
Cryo-EM, at present, requires large and expensive technology, which is housed in highly specialist environments. Lowering the energy of the electrons enables the use of a simpler, and cheaper, electron gun. The new detector, named C100, is the critical first step in this democratisation of the method.
LMB Director Jan Löwe said, “Making cryo-EM better and more accessible will enable it to be used by everyone to understand biological mechanisms and diseases, and to develop drugs more easily, even when the most complex and currently intractable molecules are involved. Decades of development at LMB and collaboration with STFC have helped create this truly unique opportunity. We are very excited for The Rosalind Franklin Institute to join in to take this work to the next level, given the Franklin’s strong focus on the interface of physics and engineering to enhance biomedical sciences.”
Cryo-EM for everyone
Chris and Richard believe that 100 keV electron cryo-microscopes could be 10 times cheaper than current versions while delivering the same results for single particle cryo-EM – at additional costs of around £50,000 to set up the room (instead of the £500,000), and running costs at 5% of the current level.
Making the technique accessible to more people increases the opportunities for new advances, said Richard, “Bringing down the barriers to access these microscopes means we can bring cryo-EM to many, many more academics around the world so they can look at samples in more detail, try new approaches and improve our understanding of human diseases.”
Marcus French, Head of Detector and Electronics at STFC’s Technology Department, has worked with Richard throughout his journey in pioneering the 300 keV camera systems. “It has been both exciting and rewarding. This project is the key to a new cryo-EM platform that will unlock the technique to a much wider research community. This will drive a step change in the rate of scientific discovery in this dynamic field and so aligns perfectly with STFC’s ambition to maximise the societal impact of the UK’s national science programme,” added Marcus.
The ultimate goal is to encourage faster scientific progress by bringing a quick, simple and reliable cryo-EM to medical research laboratories and drug companies around the world, allowing a massive shift in the accessibility of this revolutionary technique. In the UK, for example, the national cryo-EM facility, there is a six week wait to get any time on a 300 keV microscope and a very significant amount of preliminary data.
The mission of The Franklin, funded through UKRI by the Engineering and Physical Sciences Research Council, is to develop and apply disruptive new technologies in the physical and engineering sciences to transform the UK’s life science research and pharma sector.
Creating new drugs has never been slower or more expensive, but the need is growing faster than ever. The use of cryo-EM to study biological samples – the development of which won Dr Henderson his Nobel Prize – is a key technology in the process.
Professor James Naismith, Director of the Rosalind Franklin Institute says: “When Richard first told me about their idea for a revolution in accessibility of cryo-EM I knew this was exactly the kind of problem that The Rosalind Franklin Institute exists to help solve. C100 is a perfect example of paradigm shifting innovation in life sciences.”