Background
Dr Owen Marshall has been an independent group leader and Senior Research Fellow at the Menzies Institute for Medical Research, University of Tasmania, since 2016. Marshall has used the fly brain as a means to understand development and disease for the last decade, focusing on the gene regulatory and epigenetic changes underlying these processes. His research seeks to understand how our brains form, and uncover the causes of diseases such as Alzheimer's disease and brain cancer.
Abstract
The cells in our brain need to maintain a difficult balance, preserving their differentiated identities while retaining sufficient transcriptional flexibility to respond to ageing, stress and disease. Repressive chromatin is central to this balance, but silent states are generally classified by their molecular composition rather than by their capacity for future activation. Beyond the early stages of development, we still understand little about how different forms of repression determine whether silent genes remain inaccessible, or whether they can be reactivated during stress and disease.
Using cell-type-specific chromatin and transcriptional profiling in Drosophila, in normal and disease model brains, combined with genetic manipulation, we find that the two major cell types in the brain - neurons and glia - use surprisingly distinct forms of epigenetic repression. Neurons lock down their unused genes in a stable but potentially restrictive silent state. Glia instead retain developmental genes within more responsive forms of silent chromatin, allowing plasticity to better respond to challenges in the ageing brain, but also creating a potential environment for cancer.
In this seminar, Marshall will discuss their recent findings on these epigenetic and transcriptional changes, and how these differences may create opposing vulnerabilities in Alzheimer’s disease and glioblastoma brain cancer.