Neuroimmunology Group, Institute for Neuroscience and Muscle Research, Kids Research Institute at the Childrne'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: K North (depthead), K North (head), S Cooper (inmr-dmrt), N Clarke (inmr-mmdt), B Barton (inmr-nft), R Webster (inmr-nft), J Burns (inmr-crt), E Oates (inmr-crt), R Dale (inmr-nit), F Brilot-Turville (inmr-nit), S Pillai (inmr-nit), B Owler (inmr-nst)
Funding: NHRMC, the Star Scientific Foundation, Multiple Sclerosis Research Australia, Tourette Sydnrome Association USA
Research approach equipment: Our focus is to identify new targets of antibodies and to study the role of these antibodies in the pathogenesis of brain immune-mediated diseases in children. 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 translational research center for children associated with the University of Sydney. It is located in a brand new building besides the Children's Hospital at Westmead. Also present on the Westmead campus are the Westmead Millenium Institute and the Children Medical Research research Institute. The three institutes share state-of-the-art facilities including flow cytometry, imaging, genomics, and proteomics cores.
Publications:

MohammadSS, SinclairK, PillaiS, MerhebV, AumannTD, Gill D, Dale RC, Brilot F.Herpes Simplex encephalitis relapse with chorea is associated with autoantibodies to NMDA Receptor or Dopamine-2 receptor. Movement Disorders Journal. accepted for publication on July 1st 2013. (I.F.: 4.558)

Amatoury M, Merheb V, Langer J, Wang XM, Dale RC, and Brilot F. High-throughput flow cytometry cell-based assay to detect antibodies to N-Methyl D-Aspartate receptor or Dopamine-2 receptor in human serum. Journal of Visualized Experiments. accepted for publication on March 27th 2013. In press.

DaleRC, Pillai S, & Brilot F. Cerebrospinal fluid CD19+ B cell expansion in NMDAR encephalitisDev Med Child Neurol. 2013; 55(2): 191-3(I.F.: 3.09)

DaleRC, MerhebV, Pillai S, WangD, CantrillL, MurphyTK, Ben-PaziH, VaradkarS, AumannTD, HorneMK, ChurchAJ, FathT, & Brilot F.Antibodies to surface dopamine 2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012 vol. 135(11): 3453-3468 (I.F.: 9.45). This manuscript’s findings are highlighted in 1) Scientific Commentary written by Min Ling and Angela Vincent in Brain 2012:135; 3201-3205, 2) “Hot Topics” commentary written by Bettina Balint and Kailash Bhatia in Movement Disorders Journal, 2013: 28 (6); 733.


Understanding how autoantibodies are pathogenic in multiple sclerosis and demyelinating diseases in children

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. 3-10% of MS patients have their first demyelination event in childhood. Thus, paediatric patients offer a good opportunity to understand early event leading to demyelination.

Recently, we have used a novel assay, which uses cells expressing the correctly folded native MOG protein at the cell surface. We have then detected high titers of anti-MOG antibody in the serum of 50% of children with a first episode of demyelination, compared to 0% of controls. This detection of anti-native MOG antibody in children helps us to define the subgroup of patients that may benefit from therapy targeting humoral immunity with the aim of preventing progression to MS. We next would like to determine whether anti-MOG antibody are pathogenic and participate in the demyelinating process.

A cellular model has been engineered to express MOG. The expression of MOG will be determined using western blotting and immunocytochemistry. Flow cytometry and confocal microscopy will be used to determine pathogenicity of antibodies. For example, their potential action on the expression of activation markers on immune cells, such as CD107a, will be assessed by flow cytometry.

Interested students are strongly advised to contact the project supervisor to discuss potential honours and Ph.D. projects (Fabienne.brilot@sydney.edu.au).


Discipline: Pathology
Co-supervisors: Russell Dale
Keywords: Multiple sclerosis, Antibody, Neuroimmunology
Contact: Email Fabienne Brilot-Turville