Myelin is a protective, fatty layer that surrounds nerve cells and supports their function. In MS, myelin is damaged, and the cells responsible for making it, called oligodendrocytes, decrease in both number and effectiveness. A promising approach to treating MS is to encourage the regrowth of myelin (remyelination), by stimulating immature cells, known as oligodendrocyte precursor cells, to develop into mature oligodendrocytes that can regenerate this protective layer.
Mr Jack McDonald’s research focused on a protein called GPR17, which acts like a sensor on immature oligodendrocyte cells that have the potential to become myelin-producing cells. This protein plays a crucial role in helping these cells mature, making it a potential target for drugs that could promote myelin repair in MS. While evidence suggests GPR17 could be effective in promoting remyelination, we still don’t fully understand how it works or how drugs might act on it.
Mr McDonald investigated the pathways affected by drugs targeting GPR17 to learn more about how this protein contributes to myelin repair. Using genetic tools, drug-based methods, and advanced cell models, the goal of his PhD was to clarify GPR17’s role in remyelination. By uncovering how GPR17 influences myelin formation, Mr McDonald hopes to inform future drug development, not only for GPR17 but also for other proteins involved in the repair of myelin in MS.
This project has made significant progress in understanding how drugs targeting GPR17 may support myelin repair in MS.
A range of laboratory models were established to study GPR17 and test potential drug effects, including engineered cell systems, oligodendrocyte cell lines, fresh cells from laboratory models, and human stem cell-derived models.
The project also developed new tools to study oligodendrocyte development in greater detail. In particular, a single-cell imaging and analysis method was established to track changes in cell shape and proteins on the surface of the cells as they mature.
These advances have improved the ability to detect subtle effects of different drugs and will support future work in the field.
A key finding is that GPR17-blocking drugs behave in more complex ways than previously thought. Although they act at the same target, they can affect cell signalling differently, suggesting that they may not all be equally effective for promoting myelin repair.
This finding is shaping the next stage of the research, with Mr McDonald now investigating a naturally occurring variation of GPR17 to better understand how different signalling patterns affect oligodendrocyte development. Mr McDonald hopes to continue this work following PhD thesis submission in 2026.
Overall, the project has generated important new knowledge about GPR17, established useful experimental tools, and may help guide the development of more effective drugs to repair myelin in MS.
Updated 31 March 2026Â
Dr Greg Stewart
Associate Professor Jess Nithiananatharajah
$70,000
2025
2 years
Past project
