Investigating the Neuronal Functions of Putative Tau Interactors

As the ageing population is increasing, neurodegenerative disease are becoming an increasing burden. A large class of neurodegenerative diseases are the Tauopathies which are diseases where the physiology of Tau changes. Despite many attempts to develop therapeutics for the Tauopathies, there has been no successes which suggests we are missing key information about Tau’s physiological and pathological roles. Since Tau was first discovered, it has been identified as a protein which binds microtubules as a microtubule stability regulator. However, in recent years its apparent that Tau’s complete function is more complicated and is not limited to microtubule regulation. To understand Tau’s full function, understanding the interactome of Tau is necessary. To assess this, our lab carried out a BioID Mass Spectroscopy experiment where human and fly Tau BioID constructs were expressed in young and old fly brains. Proteins which come close to Tau are then tagged with Biotin, which can be separated and analysed by Mass Spectroscopy. Unsurprisingly, many of the proteins identified were classified as “Microtubule Binding”, owing to Tau’s microtubule localisation. Interestingly, this also included proteins identified by their gene ontology as “Protein Folding”, “Oxidation and Reduction” and “RNA Binding”. My project is to investigate some of these candidates by assessing 1) If any of the candidates influence neuronal cell biology? 2) Is their influence on cell biology a result of a genetic interaction with Tau? 3) Can any of the candidates influence Tauopathy models?