Research fellow identifies key
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
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.