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Research fellow identifies key
proteins in MS

 

Dr Linda Ly from the University of Sydney was awarded a postdoctoral Fellowship funded by the Trish MS Research Foundation in 2012.

Over three years, Dr Ly has examined proteins in brain tissue affected by MS in order to better understand the processes at work in the disease and identify potential targets for therapy.  

   

Dr Ly looked at tissue taken from MS lesions at different stages of the process of the myelin loss and myelin repair and compared these to unaffected areas of the brain. Using brain tissue from the MS Research Australia Brain Bank, Dr Ly’s work has used cutting edge proteomic techniques to rapidly identify the thousands of proteins present in brain tissue.  This provides an unbiased way to identify proteins that might be affected in disease. Looking at protein profiles during remyelination is especially important, since the failure of myelin repair is a key contributor to the accumulation of disability in progressive MS.

Dr Ly has now completed her three year fellowship and in this time identified 156 proteins that were different in the MS lesions. Using sophisticated statistical ‘bioinformatic’ methods, this number was then reduced to 33 key proteins. These proteins were members of functional networks involved in inflammatory response, as well as cell structure and programmed cell death. Dr Ly then went on to further characterise seven of the most important proteins more fully within the tissue. Using specialised microscopy techniques and another method, known as selective reaction monitoring using mass spectrometry, she examined these proteins within chronic and late-remyelinating lesions.

Dr Ly was able to confirm the abundance changes for two of the proteins. The proteins, STMN1 and GSN, may be involved in remyelination. STMN1 interacts with microtubules, which are structurally important to myelin. GSN is involved with a number of cellular processes and may be involved with myelin formation during brain development. This validation process will enable the identification of the most promising candidate molecules that may be targets for developing potential treatments.

Dr Ly has completed a large amount of work in her three years. Dr Ly’s work represents one of the first studies to generate protein data sets from remyelinating MS tissue that also encompasses comparisons with surrounding tissue. She has also developed a number of technical methods to successfully examine frozen and paraffin embedded brain tissue with proteomic techniques. This work lays the foundation for further validation of molecules which may represent good treatment targets for progressive MS.

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