I grew up in Australia (Melbourne) and the UK. As a teen, I was an English Schools javelin champion. My career working in MS genetic research spans 20+ years, including six years at GlaoxSmithKline, where I used pharmacogenetic research to contribute to the clinical development, and eventual regulatory approval, of two medicines for treating HIV and plasmodium vivax malaria infection.

My first post-doctoral studies were conducted at the Wellcome Trust Centre for Human Genetics (Oxford, UK), where I worked on gene discovery for a rare neurological disease. During this period (mid-late 90s), gene technology developments meant that similar work on common human diseases was becoming feasible. Two studies published in 1996, describing the first genome-wide scans for MS susceptibility genes, whetted my appetite for working on MS. In 1999, I moved back to Melbourne to get started. The rest is history!

Research leading to the development of disease modifying therapies for relapsing-remitting disease has been a game-changer for people living with MS. From a genetics perspective, I believe we now have a good understanding of the genes and mechanisms that predispose a person to developing MS, which has contributed to knowledge driving medicines development. In recent years, the genetics community has focussed on trying to understand mechanisms driving MS progression. In the near future, I’m confident that genetic research will contribute to medicines development for progressive MS.

This project brings together knowledge and capability my team has developed with MS Australia support, which enables us to detect and characterise DNA sequence changes (somatic mutations) on a genome-wide scale in single neurons and oligodendrocytes isolated from post-mortem MS tissue. From this work, we have observed increased numbers of somatic mutations in cells that reside in inflammatory demyelinated lesions, which we hypothesise have the potential to impact functionally important genes and drive MS progression. This project seeks to integrate somatic mutation data in brain cells with genetic data from large population-based studies (GWAS) and single nucleus RNA-seq to identify genes that may be potential drug targets for progressive MS. Functional studies of selected candidate genes in neural iPSC-derived brain organoids (disease modelling) will then be used to determine the impact of these genes on myelination and remyelination, with a view to providing early pre-clinical target validation evidence.

Of the 14 disease modifying therapies currently available for MS, all are immunotherapies and only two are approved for treating progressive MS. The proposed work is important because it seeks to address this clinical unmet need through the identification of therapeutic targets that may be translated into medicines for progressive MS. It is envisaged that potential medicines developed on the back of this research would impact neuroprotection and/or myelin repair, thereby slowing or preventing disease progression and improving the quality of life for people living with MS.

The most enjoyable aspect of lab work is knowing that you are doing something worthwhile, and that any findings you make are (most likely) a world-first discovery. The thought that our research could one day benefit the lives of people living with MS is the major motivator. A big challenge facing myself and other MS researchers remains the lack of investment by the federal government in MS- and biomedical research in general. This is why MS Australia and its donors are so crucial for maintaining and growing MS research in this country.