Approximately 80 per cent of new drugs fail when they reach clinical trials, as researchers are unable to fully investigate their effects within living organisms before this stage.
Now a new £30m electron microscopy project is aiming to allow researchers to see how a particular drug works within a patient at a cellular level, before it reaches clinical trials.
The project, led by the Rosalind Franklin Institute and including Thermo Fisher Scientific, will develop technology designed to create 3D images of cells at very high resolution.
The technology is based on a technique known as cryogenic electron tomography (cryo-ET), which builds up a 3D image by stitching together multiple 2D images of samples that have been flash frozen at less than -180oC, according to Professor James Naismith, director of the Rosalind Franklin Institute.
“In this large volume technique, we can go further than current technology allows – creating images of whole cells, and cells in tissues,” he said. “These cell-to-cell interfaces are where a lot of incredibly important biology happens – where drugs are taken into cells, and where cells communicate, sending and receiving signals.”
Existing cryo-ET systems can only handle very small samples, such as parts of cells. In contrast, the five-year project is aiming to speed up the technique to allow it to process much larger samples, including patient biopsies.
“The large volume allows us the potential to use patients’ samples, and see for the first time the molecular effect of a drug in a cell patient-by-patient,” said Naismith. “This could be really important for patients whose diseases are caused by misfolded proteins – there are drugs called chaperones which can help them fold correctly, and this technique would allow a doctor to check that the protein was being fixed.”
The project will require the development of new and incredibly precise techniques for preparing and handling samples of human tissue, Naismith said.
It will also involve the design of new electron microscopy techniques to speed up the imaging process and collect the huge amounts of data.
New machine learning technology will also be needed to process the data. To this end the team will be working with the Electron Bio-Imaging Centre (eBIC) at Diamond Light Source in Oxfordshire, which has considerable expertise in applying machine learning techniques to large datasets, Naismith said.