Proteomics of MS

This national research project aims to discover the proteins involved in the development of multiple sclerosis (MS). It is the first of its kind in Australia and one of the first of its kind in the world.

 

It is a major national MS collaboration between three Australian universities and the Sir Charles Gairdner Hospital, with the University of Adelaide as lead institution. Commencing in 2010 the project will be funded over four years through the Research Council's (ARC) Linkage Projects funding scheme in partnership with MS Research Australia (MSRA).

 

"With MS, there are a number of major stages that occur in the disease, including activation and remission," says Prof Shaun McColl, Deputy Head of the School of Molecular & Biomedical Science at the University of Adelaide.

 

"At each of these major stages, certain genes are activated.  Those genes generate proteins, and we believe these could have the effect of switching the disease on and off.  If we can discover the key proteins and their roles in the development of MS, we could go a long way towards finding potential treatments or cures for the condition,"

 

Most research to date has focussed on investigating a limited number of specific molecules and this has resulted in slow progress in our understanding of the pathogenesis of MS. 

 

Proteomics is the large-scale study of proteins and their structures and functions. It utilises methods that allows the simultaneous capture and study of thousands of proteins in a biological system at any given time – the proteome.

 

This project aims to dentify specific molecular changes in the CNS proteome that correlate with different stages of disease in MS. The result of this research is likely to lead to the identification of new proteins that can be targeted for the development of new therapies and diagnostics for MS.

 

One of the major cell types believed to control the damage to the central nervous system during MS are the T lymphocytes (white blood cells), which accumulate in the CNS. To date, the team has completed the first global assessment of the proteome of T lymphocytes that invade the central nervous system in a laboratory mouse model of MS that mimics the chronic-progressive features of MS. 

 

They have also compared the proteomes of unactivated T lymphocytes and those isolated from the brain and spinal cord of mice with either mild or severe disease symptoms.  The result of this experiment is presently being analysed using powerful statistical computer tools, called bioinformatics, which indicates the potential involvement of a number of proteins not previously implicated in MS.  

 

Once the bioinformatic analysis is complete, candidate proteins will be selected for further experimental analysis to determine whether they are likely to be good therapeutic or diagnostic targets for the treatment of MS. 

 

A second experiment is also underway to reveal the T lymphocyte proteome in a different model of MS which will also include the remission disease phase. Processing of the samples from this second major experiment will be completed within the next 2 months and again, will be followed by bioinformatic analysis.

 

Proteomics experiments are very time consuming as each experiment takes at least 6-8 months, but the indications so far are that we are obtaining a unique view of the disease process that occurs during autoimmune inflammation of the central nervous system.  Continuation of this research over then next 3-5 years is essential.