Nikhil J. Pandya will defend his thesis ‘Structural and functional characterization of glutamate receptor complexes’.
In his thesis, Nikhil first performed a biochemical purification of the synapse and the postsynaptic density from different brain regions. He was able to identify previously unreported proteins enriched in the PSD. Next, he studied the complex that is made of the metabotropic glutamate receptor mGluR5. In order to do so, he fished out mGluR5 from a myriad of protein complexes, and showed that it forms a synaptic complex with isoform b of the protein mGluR1, a protein that is very similar in function.
With respect to the AMPA receptor, Nikhil posed the question how to tease out the AMPA receptor complexes that exist from the plethora of possible complexes of AMPA receptor auxiliary subunits. In order to resolve this, he developed a novel method called IP-BN-PAGE wherein he separated purified protein complexes under native conditions and then identified the constituents using mass spectrometry. Using this method, he identified several prevailing AMPAR complexes, some of which were not identified before. Finally, from the many AMPA receptor auxiliary subunits Nikhil focused on one of the secreted glycoproteins that interacts with AMPAR called Noelin1. He could demonstrate that it forms a high affinity complex with the AMPAR, and that it affects the way in which the AMPAR is maintained at its location in the synapse. Thus, in this thesis, he investigated the synapse from a proteomic point of view, followed by characterization of mGluR and AMPAR complexes.