The role of Vitamin D related
genes in MS
In 2016, Dr Lawrence Ong was awarded a Betty Cuthbert Postgraduate Scholarship co-funded by the National Health and Medical Research Council and MS Research Australia, with the MS Research Australia contribution provided with full funding support from the Trish MS Research Foundation. The Trish Foundation was honoured to be co-funding this important Research Project with the National Health and Medical Research Council.
Low blood levels of vitamin D seem to increase the risk of developing MS. Genetic studies have also shown that several of the MS risk genes are involved in the processing of vitamin D in the body. In addition, vitamin D levels appear to predict clinical activity in MS. The reasons for this are unclear, but may be linked to the effect of vitamin D on immune cells. Dr Lawrence Ong, a clinical immunologist, was awarded a Postgraduate Scholarship to look at the relationship between vitamin D and genes and the effect on immune cells. Specifically, Dr Ong was interested in whether vitamin D was turning genes on or off in immune cells using the vitamin D receptor – the vitamin D docking station found on cells - and a molecular mechanism known as methylation.
During his PhD, Dr Ong used a technique called modified reduced representation bisulfite sequencing that allowed him to analyse the methylation of all the genes present in the genome at once. As part of this work, Dr Ong also developed and optimised a bioinformatics pipeline to analyse the data specifically for this research project.
Importantly Dr Ong showed that methylation patterns on immune cells could be passed on as new immune cells are generated from stem cells to daughter cells. In further work he also looked to see whether exposure to vitamin D changed methylation patterns in immune cells taken from healthy adults. He was able to demonstrate a range of differences in the appearance of these cells as well as differences in the patterns of methylation. This forms a potential pathway by which environmental exposure to vitamin D may affect the function of immune cells and therefore the risk of MS.
Dr Ong will be continuing this work to delve deeper into the mechanisms involved. He is also interested in the relationship between another environmental risk factor for MS, the Epstein Barr Virus (EBV), and methylation patterns. He will use publicly available data to investigate this relationship. His initial comparisons of cells infected with EBV and uninfected cells that are either in a resting or activated state showed methylation differences that seemed to be independent of MS risk genes.
Dr Ong has presented his findings at a number of national and international conferences and was awarded a prize for his presentation and work at the European Academy of Allergy and Clinical Immunology conference. He is preparing a number of manuscripts for submission for publication in scientific journals and was also successful in securing further funding from MS Research Australia to continue this work through an incubator grant.