Clara Dieterle

Thesis Title: Imaging Neurobiology: Understanding brain disease mechanisms using multi-omics

Franklin Supervisors: Dr Felicia Green, Dr Mark Basham, Dr Matija Lagator

University: University of Manchester

University Supervisors: Prof. Nick Lockyer

External Collaborators: University of Sheffield (Dr Richard Mead), University Of Birmingham (Professor Helen Cooper), King’s College London (Professor Juan Burrone)

Familial amyotrophic lateral sclerosis (fALS) is a neurodegenerative disease leading to progressive motor neuron degeneration. Mutations in the SOD1 protein complex are responsible for 20% of fALS cases. The aim of this project is to investigate differences in omics composition in the hippocampus and motor-associated areas of the brain as well as the role of SOD1 in fALS mouse models compared to healthy controls (wt-mouse model). This will be investigated using a multi-modal approach, such as mass spectrometry imaging (MSI) and native ambient mass spectrometry (NAMS) imaging. Using these techniques will allow imaging of a variety of different chemical species including metabolites, proteins and lipids with good spatial and depth resolution, differentiating MSI from more frequently used techniques such as microscopy and immunohistochemistry. Furthermore, using NAMS, intact protein complexes can be spatially resolved and imaged. The different imaging techniques will be correlated using a superpixel segmentation algorithm for streamlined analysis, allowing faster and easier comparison as well as interpretation of data and thus providing insight into the mechanisms underlying fALS.

Clara graduated from the University of Dundee with a M.Sc. in Applied Neuroscience, focussing in her Master’s project on characterizing the efficacies and potencies of μ opioid receptor agonists, and thereby enabling the potential identification of partial or biased agonists. She obtained her B.Sc. in Molecular Medicine at the University of Regensburg and tried to characterize a model of mild repetitive closed-head injury to understand the effect of repetitive traumas on spine density and morphology at the Biomedical Centre Munich (BCM), Munich.