Using ATAC-sequencing to investigate the transcriptional regulation of the SCN in response to light

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

The suprachiasmatic nucleus (SCN) is a small area of the brain located within the hypothalamus, and is responsible for orchestrating the light/dark cycle of all cells throughout the body, to ensure coordinated rhythmic outputs. The project aims to exploit a new next generation sequencing technique known as Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) to investigate the regulatory networks of cells within the SCN. It is hypothesised that the chromatin structure within nuclei of cells in the SCN, changes at different times of the day, to allow circadian entrainment to varying light/dark cycles. ATAC-seq will identify changes in chromatin structure, gaining insight into the genes that are being switched on and off at different points of the light/dark cycle. Disruption to a normal circadian rhythm is often endemic in todays 24 hour society; therefore understanding the fundamental biology underlying the circadian clock, and its regulation has never been more important.

The project will cover the following BBSRC Priority Areas:
Data driven biology
Food, nutrition and health
Healthy ageing across the lifecourse
The replacement, refinement and reduction (3Rs) in research using animals
Welfare of managed animals
Brain Science and Mental Health
Lifelong Health and Wellbeing

WUB, ENWW

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 01/10/2015 30/09/2023
1757534 Studentship BB/M011224/1 01/10/2016 30/09/2020 Steven Paul Walsh
 
Description I have successfully developed a protocol to carry out ATAC sequencing with mouse SCN brain tissue, and following analysis, I have determined that chromatin does indeed change its state of 'openness', following my treatment. I am now repeating the experiment to confirm my result, and hopefully improve data quality to a publishable standard.
Exploitation Route Understanding the chromatin state within the SCN, will help to give a greater understanding about how mammals entrain to varying light dark cycles, this may in turn lead to better treatments for people suffering sleep disruption, such as shift workers.
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