Michael Grange | “Structural cell pathology: imaging the sub-cellular molecular makeup of the brain”
Cellular and molecular neuroscience \ Manfred Eigen lecture theatre
Studying biological structures within intact tissues requires methods that can prepare very thin sections while preserving the sample’s native state, which remains technically challenging. Samples must be rapidly frozen to retain hydration and minimise preparation artifacts. I will describe approaches that use advanced ion beam and electron microscopy techniques to simplify sample preparation and enable high-resolution structural analysis. When combined with complementary imaging methods, these approaches allow specific features to be targeted within large, frozen tissue samples. I will outline how we are applying these methods to study early changes associated with Alzheimer’s disease, including protein aggregation and cellular damage, and discuss how cryo- electron microscopy can be extended to clinical samples. Finally, I will highlight the broader potential of these techniques for future developments and their integration into emerging multimodal imaging workflows, including applications to human tissue.