Aim 1 – Establishing the techniquesThe core aim of this project was to develop state-of-the-art proteomics technologies for the Australian MS research community and this has been successfully achieved. The Adelaide Proteomics Centre has developed two highly sensitive and accurate technologies for comparative proteomics experiments. In addition, they have established the innovative new proteomics technology known as imaging mass spectrometry that is available in only a very few proteomics facilities in the world. This allows a molecular profile to be generated and matched to microscopic features within the tissue, for example, across the width of an MS lesion.
Crucially, the team have demonstrated that this technology can be applied to both fresh-frozen tissue as well as archived, formalin preserved tissue which opens the way to study human tissue samples that have been collected over a number of years. The team will shortly submit a manuscript on the techniques for publication in the peer-reviewed scientific literature.
Aim 2 – Gathering the data
One of the major cell types believed to control the damage to the central nervous system during MS are the white blood cells known as T lymphocytes, which accumulate in the brain and spinal cord (CNS). Over the first two years of this project, the team applied the new mass spectrometry platforms to conduct the first two global assessments of the proteomes of T lymphocytes invading the CNS during MS-like disease in the mouse.
The team have identified over 300 proteins in a chronic-progressive model and almost 1500 proteins in the relapsing-remitting model of MS, many of which have not previously been implicated in MS. The team are currently conducting a deeper analysis of the data using a bioinformatics approach to narrow down the most significant molecules that warrant further investigation. Three proteins have proved to be of particular interest, which are the subject of ongoing experiments.
Work also continues in using the new imaging mass spectrometry technique to determine protein changes across lesions in the mouse model of MS to provide vital information on the changes that occur at the interface of the lesion and the neighbouring normal tissue.
Aim 3 – Determining the therapeutic and diagnostic potential of identified proteins
Excellent progress is now being made in further investigations in the individual projects of the collaborating MS researchers. The imaging mass spectrometry technique has now been optimised in samples of healthy human optic nerve. In collaboration with Prof Bill Carroll, from the Sir Charles Gairdner Hospital in Perth, analysis will soon commence in human optic nerves affected by MS.
Dr Judith Greer at the University of Queensland has been developing a new form of therapeutic agent directed at specifically suppressing the immune responses against the most abundant myelin protein in the central nervous system, myelin proteolipid protein (PLP). Dr Greer has shown that an immune response to this particular protein is associated with MS lesions in parts of the brain that control balance.
In conjunction with Drs Michael Barnett and Ben Crossett from the University of Sydney, the team will also shortly begin analysis of human MS lesions using complementary mass spectrometry techniques, including imaging mass spectrometry.
The breadth of these projects and the combined expertise of the investigators will see some very exciting progress and insights into the molecules that lie at the heart of MS pathology and will allow the development of highly targeted new treatments for MS.
Updated: 06 January, 2010