Tobias David Merson
BA (Qld), BSc(Hons) (Qld), PhD (Melb)
NHMRC/MSRA Betty Cuthbert Fellow
Contact Details
Email: | |
Phone: | +61 (0)3 8344 6386 |
Fax: | +61 (0)3 8677 9826 |
Research Interests
- Cell fate determination and lineage commitment of neural stem and progenitor cells in the normal and diseased brain
- Understanding the functional significance of adult neurogenesis
- Cellular and molecular control of remyelination of the demyelinated central nervous system
Current projects
My research aims to understand how the fate of neural stem and progenitor cells (NSPCs) is regulated in the normal and diseased central nervous system (CNS). NSPCs emerge early during neural development and rapidly divide and subsequently differentiate into the cells that comprise the mature adult CNS, a process called neurogenesis. Neurogenesis persists throughout adult life due to the retention of a small population of NSPCs in the subventricular zone (SVZ) of the postnatal brain. These adult NSPCs are capable of long-term self-renewal and give rise to progeny that differentiate into mature neural cells.
In addition to serving an important role in normal neural turnover and function, accumulating data indicate that the modulation of adult neurogenesis contributes to endogenous repair mechanisms in response to acute and chronic forms of neural trauma, disease and degeneration. Understanding how NSPC function is regulated in the normal and diseased brain may provide a route for enhancing the potential of NSPCs to repair the diseased/damaged CNS.
1. Regulation of neural stem/progenitor cell fate by IL6-family cytokines
Soluble factors found in the extracellular environment of the SVZ can influence how NSPCs behave and the types of cells that they produce. We are investigating the role of the gp130 signalling pathway in modulating NSPC function. The gp130 pathway is stimulated by soluble factors such as LIF. LIF acts on the cell by binding to a protein complex comprising LIF receptor β (LIFRβ) and gp130 receptor. We have shown that activation of this complex by LIF or related cytokines enhances the self-renewal capacity of NSPCs. We are investigating the role of gp130 signalling upon NSPCs by utilising conditional knockout strategies to delete genes that encode positive and negative regulators of gp130 signalling in NSPCs.
2. Remyelination of the demyelinated brain
Demyelination is a key pathological feature of the human disease multiple sclerosis (MS). MS is characterised by the death of specialised glial cells called oligodendrocytes. The myelin produced by oligodendrocytes serves to insulate the axons of nerve cells. When nerve cells become demyelinated due to oligodendrocyte death, they become dysfunctional. We are using sophisticated transgenic approaches to characterise the responsiveness of NSPCs, resident oligodendrocytes and local oligodendrocyte progenitor cells during remyelination of the demyelinated white matter. The project aims to examine the potential for NSPCs derived from the SVZ to replace oligoendrocytes that are lost during disease and to characterise the molecular events responsible for the formation of new oligodendrocytes from oligodendrocyte progenitor cells and NSPCs.
Laboratory Techniques
Mouse models of CNS demyelination, generation of transgenic mice, cell culture (neurospheres, oligodendrocyte progenitor cells), cell transfection, flow cytometry, confocal imaging, fluorescence immunohistochemistry, quantitative real-time PCR, Northern & Southern blot analysis, DNA cloning.
Additional Information
Research Assistant
Mr Sze Woei Ng - BSc (Melb), MBB (La Trobe)
Students
Ms Laura-Jane Oluich (PhD, 2006-, co-supervised with Dr H. Cate and Prof T. Kilpatrick)
Ms Jo Anne Stratton (PhD, 2009-, co-supervised with Prof T. Kilpatrick)
Ms Michelle Mun (BSc(Hons), 2010-, co-supervised with Prof T. Kilpatrick)
Previous students
Ms Davina Mareels (BSc(Hons) 2008, co-supervised with Prof T. Kilpatrick)
Mr Reuben Finighan (UROP 2007, co-supervised with Prof T. Kilpatrick)
Collaborators
Dr Tara Walker (Queensland Brain Institute, University of Queensland)
Dr James Bourne (Department of Anatomy and Developmental Biology, Monash University)
Honours and PhD projects available
- Tracking neural precursor cell migration following central demyelination
- Investigating the development of oligodendrocyte chains in CNS white matter
For more information follow the link below to Neuroparkville research projects and search the scientist field with 'Merson' (www.neuroparkville.org.au).
Research Images
Selected Publications
Search Pubmed
Hewitt CA, Ling KH, Merson TD, Simpson KM, Ritchie ME, King SL, Pritchard MA, Smyth GK, Thomas T, Scott HS, Voss AK (2010) Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome. PLoS One (accepted).
Merson TD, Binder MD, Kilpatrick TJ (2010) Role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination of the CNS. Neuromolecular Med 12(2):99-132.
Cate HS, Sabo JK, Merlo D, Kemper D, Aumann TD, Robinson J, Merson TD, Emery B, Perreau VM, Kilpatrick TJ (2010) Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination. J Neurochem. Feb 27. [Epub ahead of print].
Young KM, Merson TD, Sotthibundhu A, Coulson EJ, Bartlett PF (2007) p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells. J Neurosci 27(19):5146-55.
Merson TD, Dixon MP, Collin C, Rietze RL, Bartlett PF, Thomas T, Voss AK (2006) The transcriptional coactivator Querkopf controls adult neurogenesis. J Neurosci 26(44):11359-70.
Merson TD (equal first), Emery B, Snell C, Young KM, Ernst M and Kilpatrick, T.J (2006) SOCS3 negatively regulates LIF signalling in Neural Precursor Cells. Mol Cell Neurosci
Emery B, Cate HS, Marriott M, Merson T, Binder MD, Snell C, Soo PY, Murray S, Croker B, Zhang J-G, Alexander WS, Cooper H, Butzkueven H and Kilpatrick TJ (2006) Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. Proc Natl Acad Sci USA. 103(20):7859-64.
Krebs DL, Metcalf D, Merson TD, Voss AK, Thomas T, Zhang JG, Rakar S, O’bryan MK, Willson TA, Viney EM, Mielke LA, Nicola NA, Hilton DJ, Alexander WS (2004) Development of hydrocephalus in mice lacking SOCS7. Proc Natl Acad Sci USA. 101(43):15446-51.
About
Multiple Sclerosis
Multiple Sclerosis is the most common cause of neurological disability for Australian men and women between the ages of 15 and 55.