Thesis title: Probing the molecular impact of Tau pathology on synaptic integrity
Primary Theme: Structural Biology
Secondary Theme: Mass Spectrometry
Franklin supervisors: Dr Michael Grange, Dr Felicia Green
University: University College London
University supervisors: Dr Mike Devine, Dr Cara Croft
Becky’s project is an investigation into the impact of Tau pathology, a characteristic feature of Alzheimer’s disease (AD), on synaptic integrity using advanced cryo-electron tomography (CryoET) techniques. By developing and optimising the production of three-dimensional brain slice cultures (BSCs) with induced Tau pathology, her work aims to elucidate the structural disruptions and molecular changes occurring at synapses in their native environment throughout the progression of AD. Within her three-year project, she expects to bridge a gap in current knowledge of mechanisms by which neurofibrillary tangle formation alters synaptic function, highlighting conserved processes by which Tau pathogenesis regulates neurodegeneration.
Becky graduated with an MSci in Biochemistry from the University of Southampton, where she cultivated a fascination for diseases of the ageing brain. In her final projects there, she utilised a range of spectroscopic methods to biophysically characterise both the structure and aggregation kinetics of human-derived amyloidogenic proteins in Alzheimer’s and Parkinson’s disease. During a summer placement with the Molecular and Cellular Biosciences group, she developed her understanding of these biophysical techniques by attempting to simulate the solid-state NMR spectra of tau amyloids under varying biological conditions in silico. Implementing structural biochemistry as a foundation for her knowledge, Becky is enthused to develop and integrate her research experience alongside the innovative approaches of the Franklin, transforming the lives of those living with degenerative conditions