Proteomics
in MS research
In
2009, Dr Michael Barnett, and colleagues Professor Prineas and Dr Ben Crossett,
of the University of Sydney, were awarded a $278,000 project grant from the
Trish Multiple Sclerosis Research Foundation.
Professor
Prineas has received international acclaim and several major awards for his lifetime
of achievements in MS research including in 2009, the MS International
Federation’s highest accolade, the Charcot Award. Together with clinician
researcher Dr Barnett and proteomics specialist Dr Crossett, the team makes a
formidable force for progress in MS research.
While
the cause of MS remains unknown, we do know that an autoimmune response plays
an important role in disease development.
Autoimmune responses carried out by inflammatory immune cells from the
blood are generally accepted to initiate the cascade of events that lead to an
MS lesion in the brain or spinal cord.
However,
in 2008, Professor Prineas and his colleagues, sent significant ripples through
the MS research community with their discovery of evidence for sick and dying
brain cells that preceded the influx of inflammatory immune cells from the
blood. Instead, this early damage is accompanied by activation of the local
‘house-keeping’ microglial cells that clean up damaged cells.
In
order to pursue this unprecedented new avenue in MS research the team has set
their sights on identifying the earliest triggers for this damage to myelin. To
do this they have turned to high powered ‘proteomics’ technology.
Proteomics
is the study of all the proteins that are activated and deactivated, in a
particular biological situation and can amount to studying 1000s of proteins in
one go.
An important and vital step in this project has been the development and
refinement of an exciting method to extract proteins from preserved brain
tissue, specifically targeting areas within MS lesions. Dr Barnett has painstakingly developed this
highly complex, multi-step new technique. The technique, which will be of use
to MS researchers worldwide and has been presented at 4 international meetings
including PACTRIMS (Hong Kong 2009) and the Human Proteome Organisation (HUPO)
world annual congress (Sydney, 2010).
Combining
this technique with Dr Crossett’s proteomics expertise has lead the team to
identify over 80 unique proteins in tissue from MS lesions compared to tissue
from people with no neurological disease.
This is the first crucial step in a huge undertaking as these proteins
must now be individually characterised and studied.
The
work has been recently submitted for publication to the Journal of Proteome
Research. It is anticipated that the
identification of the proteins involved in the earliest stages of MS lesions
will help provide clues to the causes of MS and may lead to targeted and more
effective treatments.