Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, Kids Research Institute at the Children's Hospital at Westmead (Sydney Children's Hospitals Network)
Lab head: Dr Fabienne Brilot-Turville
Location: Kids Research Institute at the Children's Hospital at Westmead
Lab members: F Brilot-Turville (inmr-nit), R Dale (inmr-nit),
Funding: NHRMC, the Star Scientific Foundation, Multiple Sclerosis Research Australia, Tourette Sydnrome Association USA
Research approach equipment: Our focus is to identify autoantibodies and to understand their role in the brain disease. Our group is part of the Institute for Neuroscience and Muscle Research at the Kids Research Institute (the Children's Hospital at Westmead). The Kids Research Institute is a global leading USyd-affiliated translational research centre. It is located at the heart of the Westmead campus in a new building besides the Children's Hospital at Westmead. Also present on the Westmead campus are the Westmead Institute for Medical Research and the Children Medical Research Institute. The Kids Research Institute is part of the Westmead Research Hub and shares state-of-the-art Hub facilities including flow cytometry, imaging, genomics, and proteomics cores.
Dale RC*, Tantsis EM*, Merheb V, Kumaran RY, Sinmaz N, Pathmanandavel K, Ramanathan S, Booth DR, Wienholt LA, Prelog K, Clark DR, Guillemin GJ, Lim CK, Mathey EK, Brilot F. Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurol Neuroimmunol Neuroinflammation2014 May 22;1(1):e12, doi: 10.1212/NXI.0000000000000012 *Contributed equally to this work.
Pathmanandavel K, Starling J, Merheb V, Ramanathan S, Sinmaz S, Dale RC, Brilot F. Antibodies to surface dopamine-2 receptor and N-methyl-D-aspartate receptor in the first episode of acute psychosis in children. Biol Psychiatry. 2015 Mar 15;77(6):537-47
Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev. 2016 Apr;15(4):307-24
Sinmaz N, Amatoury M, Merheb V, Ramanathan S, Dale RC, Brilot F. Autoantibodies in Movement and Psychiatric Disorders: Updated Concepts in Detection Methods, Pathogenicity, and CNS Entry. Ann N Y Acad Sci. 2015 Sep;1351:22-38. doi: 10.1111/nyas.12764. Epub 2015 Jun 17
Exploring how autoantibodies are pathogenic in multiple sclerosis and demyelinating diseases in humans
Primary supervisor: Fabienne Brilot-Turville
Multiple sclerosis (MS) is a common relapsing demyelinating disease of the central nervous system (CNS). MS affects 1 individual in 1,000, and causes increasing physical and cognitive disabilities. MS has a high burden of care and results in annual 2 billion dollar cost to the Australian community. Patients are left with permanent neurological problems as the disease advances. MS primarily affects genetically susceptible young adults.
Recently, we have used a novel assay, which uses cells expressing the correctly folded native MOG protein at the cell surface. Autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG autoantibodies) have recently been recognized as biomarkers in subsets of human adult and paediatric demyelinating diseases. However, how human MOG autoantibody participate in disease pathogenesis remains elusive. We next would like to determine whether anti-MOG antibody are pathogenic and participate in the demyelinating process.
A cellular model will been engineered to mimic cells in human brain. Neurons and glial cells will be matured and co-cultured. The expression of MOG will be determined using western blotting and immunocytochemistry. Flow cytometry and confocal microscopy will be used to determine pathogenicity of autoantibodies.
Interested students are strongly advised to contact the project supervisor to discuss potential honours and Ph.D. projects (Fabienne.firstname.lastname@example.org).
Co-supervisors: Russell Dale
Keywords: Multiple sclerosis, Antibody, Neuroimmunology