Supervisors: Professor Bruno FrenguelliLink opens in a new window and Dr Daniel HebenstreitLink opens in a new window

Expected start date: October 2021 (full-time for 1 year) - alternative start date could be agreed

Location: SLS Gibbet Hill Link opens in a new window(remote working is possible)

Funding: This project is for students who can self-fund or hold their own scholarship

• The deadline for applications is: 18 September 2021

Project Description:

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.

Any application queries can be directed to b.g.frenguelli@warwick.ac.uk

Key experimental skills involved: Bioinformatic analysis of RNAseq data sets

References: Cooper DD, Frenguelli BG. (2021) The influence of sensory experience on the glutamatergic synapse. Neuropharmacology. 193: 108620. doi: 10.1016/j.neuropharm.2021.108620.

Privitera L, Morè L, Cooper DD, Richardson P, Tsogka M, Hebenstreit D, Arthur JSC, Frenguelli BG. Experience Recruits MSK1 to Expand the Dynamic Range of Synapses and Enhance Cognition. J Neurosci. 2020 40: 4644-4660. doi: 10.1523/JNEUROSCI.2765-19.2020.

Eligibility: The University’s standard entry requirements are as follows:

• You must hold a lower second class UK honours degree (2:2) or equivalent - Overseas Qualifications: UK equivalencyLink opens in a new window
• You must be able to provide 2 satisfactory academic references
• Submit an English Language test certificateLink opens in a new window (if appropriate). Please note: It is a requirement that overseas students will show that their ability to understand and express themselves in both written and spoken English is sufficiently high for them to derive the full benefit from the PhD. Please note that the requirement for admission is IELTS 6.5 (with no component below 6.0) or equivalent. More information can be found at:

http://www2.warwick.ac.uk/study/postgraduate/apply/english/

How to apply:

• Complete the online application formLink opens in a new window - selecting course code: P-C1PP - MSc Life Sciences
• Upload a transcript from your current or previous study and any other documents that you feel would support your application.
• Ask your referees to submit a reference for you. Note: when you submit your application, an email will automatically be sent to your referees requesting a reference for you. This email will contain a secure link for your referee to upload a reference for you.
• The deadline for applications is: 18 September 2021

For further information about applying to Warwick see the application FAQ'sLink opens in a new window page.