How does the autism-related protein Shank contribute to the regulation of neuronal spine plasticity?

Understanding how the brain works is a major challenge for modern biology. Synapses are the main points of communications between neurons creating billions of smart connections that dynamically change in development, learning, ageing and pathologies. The “signal processing machine” of synapses is located within the postsynaptic density (PSD) composed of a dense network of inter-connected proteins. In a healthy brain molecular interaction within PSD are finely balanced, allowing it to change in response to synaptic activation. This balance is affected in neurological disorders, such as increasingly common Autism Spectrum Disorder (ASD), and through deterioration caused by ageing. Solving the brain mysteries will require a new type of biological researcher who can combine structural, molecular and cellular approaches into innovative research strategies. This PhD studentship will offer unique training opportunities, extending from structural to molecular biology, through cellular neuroscience to understanding how neuronal postsynaptic spines are modified by mutations in Shank3, a gene highly implicated in ASD. We recently discovered new Shank3 interactions that connect it to the main signalling networks in the PSD. You will follow up these connections at the molecular level and in cortical neuronal cultures. You will investigate how complexes Shank3 forms complexes with other PSD molecules with Magnetic Resonance Spectroscopy and X-ray Crystallography, and how these complexes control PSD properties in neurons with latest methods of Fluorescent Imaging and Electron Microscopy, using state-of-the-art research facilities at Liverpool and Newcastle. The two supervisors are perfectly placed to provide this training, with their highly complementary expertise in structural and cellular biology. The student will also benefit from the exposure to life and science in two Universities and cities, as well as the opportunity to interact and possibly visit longstanding collaborators in other European countries. Besides the scientific training, the student will also be encouraged, for instance, to participate to outreach activities and learn how to communicate science to the lay public and to develop alternative skills (e.g. entrepreneurship, management, media, ethics) through courses and seminars regularly held at the Universities. All this will provide the student with a wide range of skills applicable to academia, industry or other sectors (e.g. management, media, finance etc.).

For further information see the website: https://www.liverpool.ac.uk/integrative-biology/

To apply:
Please submit a full CV and covering letter directly to [Email Address Removed]