Murray laboratory: Myelin biology
Associate Professor Simon Murray
+61 3 8344 5813
Myelin is the insulating sheath wrapping around many axons in the peripheral (PNS) and central nervous system (CNS). It is essential for the rapid and efficient transmission of neural signals along the axons, and provides metabolic and trophic support to the axons that it surrounds. Human demyelinating diseases, such as Multiple Sclerosis (MS), have a devastating impact on quality of life. It is the failure of the nervous system to repair myelin after a demyelinating insult that leads to disease progression and increasing disability. In addition, myelin damage is a common pathological feature of many neurodegenerateive diseases. However, there is currently an incomplete understanding of the molecular and cellular events that initiate, promote and maintain the interactions between neurons and glial cells that are vital for myelination in both the PNS and CNS.
Our laboratory is particularly interested in understanding the molecular cues that are vital for myelination during development, and myelin repair after injury as well as developing new therapeutics for promoting repair after myelin injury. We use a variety of molecular, cellular, biochemical, genetic and confocal imaging techniques in combination with behavioural analyses and animal models of demyelinating disease to investigate these events.
Honour Projects 2021
PROJECT #1: CAN MIMETICS OF BDNF PROMOTE REMYELINATION AFTER INJURY?
In CNS demyelinating diseases, oligodendrocytes (the cells that generate myelin) progressively die. However, they possess an innate capacity to regenerate themselves and repair the lost myelin. Unfortunately, over time and repeated demyelinating events, this capacity for regeneration and repair reduces. We have identified that BDNF plays an important role in myelin development and repair. Building on these findings, we have developed novel low molecular weight peptides designed to selectively mimic the agonist properties of BDNF. This project is multifaceted in that it aims to use in vitro assays to optimise and characterise novel next-generation peptides, and use in vivo assays to investigate whether these novel BDNF mimetic peptides can promote myelin repair using animal models of nervous system demyelination.
PROJECT #2: ANALYSIS OF MYELIN SPECIFIC TRANSCRIPTION FACTORS.
The myelin sheath -- a multi-layer membrane that wraps around many nerves in the central nervous system (CNS) -- is critical for optimal brain function. Myelin sheaths are made by cells called oligodendrocytes and most myelin sheaths are formed in early postnatal development, but new sheaths can be added throughout life in response to learning or brain injury. However, the molecular mechanisms that regulate these dynamic changes in myelin sheath growth have not been fully identified. The overall aim of this project is to identify and characterise novel molecular mechanisms that control myelin sheath growth in the CNS. We will use innovative interdisciplinary methods to identify novel ways that signaling pathways, protein interactions and transcription factors are activated to control oligodendrocyte development and myelination.
Associate Professor Simon Murray, Head of Laboratory
Rhiannon Wood, Research Assistant
Madeline Nicolson, PhD student
Sangwon Yoo, PhD student
Georgina Craig, PhD student
Dr David Gonsalvez, Monash University
2018-2021 ARC Discovery Project Grant. How neurons regulate the myelinating process
2018-2021 US Department of Defense Investigator-Initiated Research Award. Developing a Novel Neurotrophin-Based Strategy to Promote Myelin Repair in Multiple Sclerosis
2019-2020 MS Research Australia Project Grant. Promoting myelin repair in a refractory environment in vivo
2019-2021 MS Research Australia Project Grant. How neurons regulate cortical and subcortical remyelination?
2016-2018 NHMRC Project Grant. Novel strategies to promote myelin repair in the brain
2014-2017 NHMRC Project Grant. Developing a new strategy for treating peripheral demyelinating neuropathy
"Mimicking a cure", Australian Life Scientist, 14 August 2013
“Kiss Goodbye to Multiple Sclerosis” - to support “World MS Day”. The Age, edited by Ms. Kate Hagan, 26 May 2010
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For further information about this research, please contact Head of Laboratory Associate Professor Simon Murray
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