Multiple Sclerosis and Myelin Repair Group
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), and is a common cause of neurological disability, affecting over 2 million people worldwide, including over 21,000 people in Australia. Crucially, current therapies for MS, while excellent at reducing the early clinical manifestations of the disease, do not prevent the accumulation of damage to nerves. It is this damage that ultimately leads patients to enter the progressive phase of the disease, which is currently untreatable. One approach to treat progressive MS is to enhance myelin repair, promoting functional recovery and limiting the tendency for otherwise demyelinated axons to degenerate.
Our group is focused on developing new treatments that promote myelin repair. Our multidisciplinary team has expertise in myelin biology, genetics and neuroinflammation to drive our research program.
About our research
Our group works collaboratively to investigate questions ranging from basic biology, such as the effect of receptor tyrosine kinases on myelination by oligodendrocytes, through to translational research, developing novel therapeutic treatments for MS.
We use a variety of techniques and mouse models of MS, as well as directly studying the human disease. We have a number of projects available that are suitable for both honours and PhD students who would like the opportunity to explore the interface of genetics, immunology and neuroscience.
- Multiple sclerosis
- Pre-clinical models of MS
- Human stem cell culture
The TAM (Tyro3, Axl and Mertk) family
A particular focus of our research is the TAM (Tyro3, Axl and Mertk) family of receptors and their two ligands, Gas6 and Protein S. We have shown that Tyro3 modulates developmental myelination and promotes remyelination, an effect driven partially through Tyro3+ve oligodendrocytes although Tyro3+ve neurons may also be involved in this process. We have also identified that Mertk, which plays a central role in the clearance of apoptotic cells and myelin debris, is a risk gene for MS. Importantly, we have identified that the TAM ligand Gas6 plays a central role in regulating the response to myelin damage and repair. We are now focussed on developing Gas6-based molecules as a treatment for MS.
The role of microglia in MS.
In addition to our ongoing interest in TAM receptor signalling in MS, we have a strong interest in understanding the role of microglia in MS. Microglia are a type of immune cell found exclusively in the brain and spinal cord. In addition to their primary function of immune surveillance, microglia also play a vital role in supporting nerve cells and refining the connections between nerve cells. Studies focussing on microglia in recent decades have begun to identify these cells as essential in outcomes of CNS disease. In certain circumstances, microglia are able to promote brain repair; thus, they are an excellent target for the development of new treatments for MS. This project focuses on manipulating microRNA (miRNA) to enhance their protective function.
- Dr Sarrabeth Stone
Research and technical staff
- Andrea Aprico
- Negar Asadian
- Vivien Li
- Mohammad Asadian
- Zachary Mevissen
- Samyuktha Sriganesh
- Alexander D. Walsh, Sarrabeth M. Stone, Andrea Aprico, Trevor J. Kilpatrick, Brendan R.E. Ansell and Michele D. Binder (2016), ‘Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system’, doi: https://doi.org/10.1101/2022.07.12.499835.
- Blades, F., Chambers, J.D, Aumann, T.D., Nguyen, C.T.O., Wong, V.H.Y., Aprico, A., Nwoke, E.C., Bui, B.V, Grayden, D.B., Kilpatrick, T.J and Binder, M.D. (2022) ‘White matter tract conductivity is resistant to wide variations in paranodal structure and myelin thickness accompanying the loss of Tyro3: An experimental and simulated analysis’, Brain Structure and Function, 227:2035-2048.
- Akkermann, R., Aprico, A., Perera, A.A., Bujalka, H., Cole A.E., Xiao, J., Field, J., Kilpatrick, T.J., and Binder, M.D. (2017) The TAM Receptor Tyro3 regulates myelination in the central nervous system. Glia 65:581-591
- Binder, M.D., Fox, A.D., Merlo, D., Johnson, L.J., Giuffrida, L., Calvert, S.E., Akkermann, R., Ma, G.Z.M., ANZgene, Perera, A.A., Gresle, M.M., Laverick, L., Foo, G., Fabis-Pedrini, M., Spelman, T., Jordan, M.A., Baxter, A.G., Foote, S., Butzkueven, H., Kilpatrick, T.J., Field, J. (2016), ‘Common and low frequency variants IN MERTK are independently associated with Multiple Sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status’, PLOS Genetics 12(3): e1005853