Experience profoundly influences the structure and function of the mammalian brain. Positive experiences associated with an enriched environment containing toys, ladders, larger social groups and exercise wheels, have repeatedly been shown to increase the number of synaptic contacts between neurones, enhance the communication between neurones, and leads to enhanced cognition (Cooper and Frenguelli 2020). Many of these changes occur in the hippocampus, a brain region critically important for certain types of learning and memory. We have recently shown that an enriched environment strongly influences gene expression in the rodent hippocampus in a manner that is largely dependent upon the enzyme MSK1 (Privitera et al., 2020). MSK1 is activated by the brain grow factors released by enrichment and then regulates the expression of genes by activating transcription factors and influencing chromatin structure. Revealing the biochemical pathways and gene expression changes associated with enrichment is important, not only to understand how enrichment shapes the brain, but also in terms of developing drugs that may activate these processes to bring the benefits of enrichment to those with various forms of cognitive impairment.
This MScR project will extend the observations we have made by exploring a rich RNAseq data set comprising 12 experimental conditions (2 x housing (standard and enriched), 2 x genotype (wild type and MSK1 mutant), and 3 x age(young, adult and aged)). Extending the analysis pipeline developed for the young age group to the adult and aged groups will allow us to identify age-, experience- and MSK1-dependent changes in gene expression, identify common expression motifs, and home in on key changes that support the enhancement of synaptic function and cognition across the life span.
The successful candidate will have a good honours degree in Bioinformatics or a related subject, and will be competent in a range of bioinformatic analysis software and approaches, including basic command line scripting, analysis with IGV, coding in R or a similar language, and running common analysis pipelines, such as DESeq or SGseq etc, along with data visualization skills. The candidate will be given guidance on the underlying neurobiology and experimental context, but will be expected to take the lead on the bioinformatic analysis. Given the bioinformatic nature of the project, much of the data analysis could be done remotely.
Key experimental skills involved: Bioinformatic analysis of RNAseq data sets.
For more information on eligibility and how to apply, please see the following link MScR Project Title: A bioinformatic analysis of experience-dependent gene expression changes in the hippocampus across the life span (warwick.ac.uk).
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