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
Antibody to brain antigens in encephalitis in children: how to prevent disabilities
Primary supervisor: Fabienne Brilot-Turville
Brain immune-mediated diseases, such as first episode of demyelination, encephalitis, Sydenham’s Chorea, and neuropsychiatric Lupus, occur frequently and affect the brain of children. Their symptoms are depression, psychosis, sleep disorders, seizures, and a full range of movement disorders. Finding a treatment is challenging, and therefore they often lead to neurological disability. A humoral (B cell and antibody) autoimmune response has been identified in subgroups of children. The targets of the attack are important brain proteins against which antibodies are raised, such as neurotransmitter receptors, or voltage-gated ion channels. This discovery has raised new hope for the treatment of these children as humoral immunity-targeted therapies, such as plasma exchange and B cell-depleting anti-CD20 antibody therapy (Rituximab) have shown promising results in adults.
Our research program is articulated around two main arms: the first one is to identify brain antigens against which antibodies are raised in these diseases in order to provide diagnostic and treatment option. The second one is to determine whether these autoantibodies are pathogenic and participate in brain damage.
Our research will greatly improve the knowledge of B cell-dependent brain immune-mediated diseases with direct translational effects into the care of these patients.
Techniques: Cellular models have been engineered to express important brain antigens. Antigen expression will be determined using western blotting and immunocytochemistry. The binding of autoantibodies from patient and control sera will be determined using flow cytometry and confocal fluorescence microscopy. Their potential action on neuron physiology will be examined using primary cultures of murine neurons and live cell imaging.
Interested students are strongly advised to contact the project supervisor to discuss potential honours and Ph.D. projects (firstname.lastname@example.org).
Discipline: Infectious diseases and Immunology
Co-supervisors: Russell Dale
Keywords: Antibody, Neuroimmunology, Brain