Neuroepigenetics: Marshall Group
We are interested in the epigenetic makeup of particular neuronal populations within the brain, and how the chromatin structure of these neurons changes during learning and memory, neurodegenerative disease and ageing. We seek to answer questions such as: What happens to neurons during Alzheimer's Disease progression? How are memories formed and preserved? What changes occur in the brain during the ageing process?
Within a cell, the activation of genes depends ultimately on the epigenetic environment that surrounds those genes. DNA is wrapped around nucleosomes to form chromatin, which can be opened up to allow transcription factors to bind and genes to be transcribed; or condensed to shut down gene expression. By regulating the transitions between open and closed chromatin, great variation in the transcriptome of a cell can be achieved, even when expressing many of the same transcription factors.
A number of studies over the last seven years have shown that different forms of chromatin are regulated through the combinations of chromatin-modifying proteins and the epigenetic histone modification marks that these proteins read or write. Key histone modifications include the aceylation and methylation of different lysine residues in the N-terminal tail of Histone H3. Together, these combinations of histone marks and chromatin proteins create what have been termed "chromatin states", of which at least five broad categories have been identified. However, the roles of these forms of chromatin in controlling gene regulation in complex organs such as the brain remain unknown.
We use the fruit fly Drosophila melanogaster as a powerful model organism with which to study the adult brain, combined with cutting-edge tools such as Targeted DamID (TaDa) and bioinformatic analyses. Using TaDa, we can profile both the transcriptome and genome-wide chromatin states of individual subtypes of neurons within the brain with extraordinarily fine temporal and spatial control. We can also ask where key transcription factors bind in individual cell types. With cell-type specific transcriptome, chromatin and transcription factor data, we can begin to map out the regulatory networks within the brain.
- Dr Owen Marshall
- John Reeves (Honours student)
- Marshall OJ*^, Southall TD^, Brand AH. (2016) Cell-type specific profiling of protein-DNA interactions with TaDa. Nature Protocols. In press.
- Marshall OJ*, Brand AH. (2015) damidseq_pipeline: an automated pipeline for processing DamID sequencing datasets. Bioinformatics. 31(20):3371-3
- Garsed DW^, Marshall OJ*^, Corbin VD^, Hsu A^, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM. (2014) The architecture and evolution of cancer neochromosomes. Cancer Cell. 26(5):653-67
- Southall TD, Gold KS, Egger B, Davidson CM, Caygill EE, Marshall OJ*, Brand AH. (2013) Cell-type-specific profiling of gene expression and chromatin binding without cell isolation: assaying RNA Pol II occupancy in neural stem cells. Dev Cell. 26(1):101-12
* Denotes Menzies Researcher
^ Denotes these authors contributed equally to this work