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Low levels of vitamin D is a known environmental risk factor of developing MS. However, the mechanism by which vitamin D might protect against MS is largely unknown. Previous research from Dr Parnell’s research group has indicated that the protection conferred by vitamin D is likely to be driven by the way that vitamin D influences the function of a particular cell type of the immune system, known as mononuclear phagocytic cells, by regulating gene activity in these cells.
This fellowship will comprise two stages of molecular biological experiments which will define interactions of vitamin D and its partner molecule, BATF (basic leucine zipper ATF-like transcription factor) in mononuclear phagocytic cells.
In MS, the immune system attacks the central nervous system, and this research will be first to study the function of these immune cells which are known to be influenced by vitamin D. This will provide new knowledge of the disease processes underlying MS and, given that there are already an array of pharmacological molecules known to affect vitamin D function, could also rapidly pave the way for new treatment options in MS. While there are a number of MS treatments currently available, all have side effects and not all MS patients are able to be successfully treated, as such, new therapies are sorely needed.
Dr Parnell’s fellowship is looking at how genes which are known to increase the risk of developing MS respond to vitamin D. His experiments so far show that the activity of the genes varies according to which immune cell type was being tested and whether certain genetic variations are present in the DNA. For example, one MS risk gene was shown to be more active in a cell subset known as tolerogenic dendritic cells compared to inflammatory dendritic cells. Furthermore, vitamin D further increased the gene’s activity in the tolerogenic dendritic cells but not the inflammatory dendritic cells.
Dr Parnell’s work has shown that three genes, the gene known as the vitamin D receptor (important for the uptake of vitamin D), and two additional MS risk genes IRF8 and ZMIZ1, play an important role in dictating what function dendritic cells will have, and that the presence of vitamin D causes the cells to increase the activity of these genes.
Dr Parnell’s most recent work has involved identifying in more detail how these two MS risk genes drive the functions of dendritic cells, and exactly how vitamin D influences this, by determining the genes they may influence. His work has shown that vitamin D treatment results in distinct activity levels of many genes, with many overlaps but also some differences between immune cell types. Dr Parnell is currently looking at which additional genes may be responsible for this response to vitamin D. Through this work, it is hoped that alternative strategies can be identified to gain benefits from the vitamin D pathway to promote a tolerant immune system.
Dr Parnell has presented his work at national and international conferences and has contributed to a number of larger scientific studies into MS and vitamin D.
Updated: 11 June 2020
$158,000
2017
3 years
Past project
