Correlative light and electron microscopy (CLEM) combines the benefits of fluorescence and electron imaging, allowing researchers to track rare biological events in the context of cell structure. Depending on the biological question, correlative workflows can be tailored to incorporate almost any imaging modality. For example, in collaboration with Dr Eva Frickel and Dr Serge Mostowy, we imaged Toxoplasma parasites in zebrafish brain, using fluorescence microscopy, micro CT, transmission EM, Serial Block Face SEM and Focused Ion Beam SEM to locate and image the ‘needle in the haystack’ (Yoshida et al., 2020).
However, correlative microscopy tends towards ‘n=1’, largely due to the complexity of the experimental workflows and the lack of automated image analysis algorithms. To overcome this bottleneck, our technology development work has focused on improving the speed, accuracy and accessibility of CLEM. In this talk, I will discuss the benefits of preserving fluorescent proteins in cells and tissues prepared for electron microscopy, which enables ‘smart tracking’ correlative workflows, and our collaboration with astrophysicists, citizen scientists and machine learning specialists to automate segmentation and visualisation of cell organelles at the nanoscale for large-scale downstream quantitative analysis of cells in health and disease.
Dr Lucy Collinson
Dr Lucy Collinson is an electron microscopist with a background in microbiology and cell biology. She has a degree and PhD in Medical Microbiology, and carried out post-doctoral research with Professor Colin Hopkins at the MRC Laboratory for Molecular Cell Biology (UCL) and Imperial College London, investigating membrane trafficking pathways in lysosome-related organelles in mammalian cells using light and electron microscopy as key techniques. She has run a series of biological electron microscopy facilities since 2004, at UCL and then at the Cancer Research UK London Research Institute, which became part of the new Francis Crick Institute in 2015. With a team of 10 electron microscopists and 3 physicists, she oversees more than 100 research projects with more than 60 research groups within the Crick, imaging across scales from proteins to whole organisms. Her microscopy and technology development interests include volume EM, correlative imaging techniques, cryo-microscopy, X-ray microscopy, image analysis, and microscope design and prototyping. Her group is using Citizen Science to gather hundreds of thousands of annotations of EM images to train deep machine learning algorithms to automatically recognise organelles in EM images through the Etch a Cell project on the Zooniverse platform. She is committed to open science through sharing of image data, protocols, software and hardware designs. She has co-authored more than 80 research and review papers, given more than 70 invited and keynote talks, and has sat on more than 30 international advisory boards, panels and committees in advanced imaging.