innovaTEbehaviour - How do transposons alter neuronal function and contribute to behavioural diversity?

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Transposons are mobile genetic elements that are highly pervasive in most animal genomes. Some transposons remain active in the human genome, and as a consequence, every person carries their own, unique combination of transposon insertions. Transposons within introns of genes can introduce new splice-donor and -acceptor sites and thereby alter host genes by forming chimeric mRNAs - a phenomenon known as transposon exonisation. Emerging evidence indicates that these chimeric mRNAs are highly abundant in somatic tissues, including the brain. This leads to an intriguing hypothesis: transposons might alter neuronal function and introduce behavioural variation within a population. I propose to combine the latest advances in high-throughput single-cell transcriptomics, new long-read sequencing tools, and a well-established behavioural paradigm in the fruit fly to test this hypothesis. I will pursue three main aims: 1. I will generate the first single-cell resolution atlas of genomic-locus specific transposon expression from an entire brain. Chimeric transposon-gene mRNA expression will be locliased to specific cells and brain regions. 2. Using this detailed information of neural transposon expression, I will test the impact of selected transposon insertions by removing them from the genomes of fly strains using CRISPR, and employing a range of physiological and behavioural tests on these genetically-edited flies. 3. I will next investigate the combinatorial effect of multiple transposon-induced changes in the brain and assess how the transposon landscape of individual flies contributes to behavioural variation within a population. Collectively, this research aims to create a new perspective on the impact of transposons in the brain, and on their role in diversifying behaviours.