The ability of the nervous system to respond adaptively relies on modifications to existing proteins as well as changes in gene transcription and protein translation. An individual neuron in the brain possesses approximately 10.000 synapses, many of which are hundreds of microns away from the cell body. As many of the changes to environmental stimuli occur at synapses, the question arises as to how the modified synapses gain access to the new mRNAs and proteins. It is now clear that synapses possess the capacity for local protein synthesis, owing to the localization of ribosomes and mRNAs within dendrites. Previous studies have identified a relative small number of localized mRNAs and an even smaller number of locally synthesized proteins. We hypothesize that synaptic plasticity makes use of the local pool of mRNAs and newly synthesized proteins to alter its’ function. Here we propose to discover the identity of nearly all the mRNAs that are localized, “the local transcriptome”, using the deep RNA sequencing technology. Using a new high-resolution platform that makes use of “fluorescent barcodes” we will visualize individual mRNAs and quantify their abundance in the dendrites. We will also discover the proteins that are synthesized in dendrites, “the local proteome”, using a novel chemical tagging strategy that we developed. In this approach, we can identify proteins synthesized within a given cell-type (e.g. neurons), via the expression of mutant tRNA synthetase in a restricted cell population. We will then examine how plasticity sculpts the local mRNA and protein population, as we hypothesize that both the transcriptome and the proteome are dynamically regulated by ongoing synaptic events.
Field of science
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics
- /natural sciences/biological sciences/neurobiology
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Funding SchemeERC-AG - ERC Advanced Grant