Dynamic imaging of protein machinery for synaptic plasticity in neuronal dendritic spines

Lead Research Organisation: University of Bristol


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M009122/1 30/09/2015 29/09/2023
1788559 Studentship BB/M009122/1 30/09/2016 30/03/2021
Description The main focus of my project has changed a lot from when I first started. I was hopeful that I could use FLIM-FRET, a powerful imaging tool used to investigate protein-protein interactions, in order to look at the interactions of a specific protein, namely PICK1, in live neurons which had been treated with chemicals to induce synaptic plasticity, the cellular process behind memory formation. After months of trial I realised that there are too many limitations to be able to image live stimulated neurons and resolved to work with fixed samples instead. This is how I obtained my first result which indicated that PICK1 is more self-associated during synaptic plasticity. My next challenge involved finding a reliable way to look at dimers/oligomers in order to decipher the regulatory mechanisms behind PICK1 self-association. Finally, I was able to show that calcium concentration affects PICK1 dimerisation, and that this effect is probably mediated by acidic regions within the BAR domain and N-terminus of the protein. I am currently working on investigating how other factors influence PICK1 dimerisation, as well as planning to conduct my experiments using neuronal samples in order to understand the importance of the PICK1 dimer for synaptic plasticity.
Exploitation Route I believe my research is important because there is little information available about PICK1 dimerisation. Considering that the majority of proteins from the same family as PICK1 form functional dimers, it would be interesting to see how PICK1 compares to these in terms of regulatory mechanisms controlling self-association. If dimerisation and further oligomerisation is a strict requirement for the function of PICK1, it opens up new avenues for therapeutic intervention in diseases such as neurodegenerative disorders, addiction and schizophrenia. I also find value in my research as a way of getting closer to deciphering how memory works and believe my work could be continued by others in this direction.
Sectors Pharmaceuticals and Medical Biotechnology