Neurodegenerative causes explored using advanced cryoET

The Rosalind Franklin Institute (the Franklin) and leading global biopharmaceutical leader MSD are jointly investigating the regulation and malfunctioning of specific cell regulation processes implicated in neurodegenerative conditions, such as Parkinson’s disease. 

The collaboration will leverage the Franklin’s instrumentation and expertise in cryo electron tomography (cryoET), a technique by which a molecular CT scan is taken of the inside of cells to reconstruct 3D images at nanometre scale. 

“Until now, structure-based drug design has relied on studying targets purified and removed from the cellular context,” said Dr Sandra B. Gabelli, Executive Director and Head of Protein and Structural Chemistry at MSD Research Laboratories. “With cryoET, we want to explore the next frontier of drug discovery by visualising the drug targets in their native cellular context.”

The Franklin team has been developing this technology to improve the image resolution that can be achieved and increase the throughput of cellular samples. They have also developed the technique so it may be applied for imaging larger samples, so that whole cells or tissues of interest can be visualised. The technology development has been carried out in collaboration with Thermo Fisher Scientific and is funded by Wellcome. 

Dr Michael Grange, explained why this collaboration is important to the Franklin: “It’s imperative to work with industry to advance the technologies we are developing here at the Franklin and we are very excited that MSD is keen to be part of our journey. One of our core values is utility – we want to develop technologies that people want to use to achieve their own research goals, both academics and industry partners. 

"Cryogenic tomography (CryoET) is a relatively new technique with a high barrier to entry. We’re trying to widen the applications and use. So, for us, this collaboration represents an opportunity to combine our technologies with MSD’s drug discovery expertise to explore cell regulation of neurodegenerative disease processes at the cellular level.” 

Dr Darren McKerrecher, Executive Director and Head of London Discovery Chemistry at MSD Research Laboratories, said: “Enhanced cellular visualisation has the potential to enable a better understanding of underlying cell biology and help inform the pursuit of novel therapeutic mechanisms. We look forward to collaborating with the Rosalind Franklin Institute team and applying their capabilities and expertise in cryo electron tomography as we work to characterise new targets in drug discovery.”

More information online