Structural Neurobiology

Errors in neuronal proteins lead to disease. It is important to study structures of these proteins in as close as possible to their native state and in contexts that can recreate potential disease states, i.e. in genetically modified or patient-isolated systems.

Focused ion beam milling combined with electron cryo-tomography (cryoET) can unravel the molecular details of processes within cells and tissues, ultimately leading to an understanding of how changes in the structures of macromolecules in their native context impact on cellular function.

The formation of neuropathic phenotypes in-situ is poorly understood. We are developing approaches to investigate the morphological and structural changes that occur within brain tissues during the development and onset of neurodegenerative disease using cryoET. The formation of inclusion bodies and neurofibrillary tangles are well-known and prominent features of late-stage disease; however, we aim to understand the molecular changes that occur in proteins that give rise to these features at different stages of disease in-situ. We are developing approaches to image some of these molecular details in human patient derived samples, so that we can best understand what early disease looks like.