The role of Vitamin D related genes in MS

Dr Lawrence Ong

The Westmead Institute for Medical Research, NSW

January 2016

specialisation: Genetics

focus area: Causes and Prevention

funding type: Scholarship

project type: Investigator Led Research

Summary

Low blood levels of Vitamin D are known to be associated with the risk of developing MS. We also know that several known MS risk genes are involved in the biological processing of Vitamin D. Vitamin D3 levels appear to predict clinical activity in multiple sclerosis. The reasons for this are unclear, but may be linked to the effect vitamin D has on the activity of immune cells. The vitamin D docking station, or receptor for vitamin D is found in a subset of immune cell genes allowing vitamin D to change the activity of these genes.

Dr Ong’s PhD scholarship is co-funded by the National Health and Medical Research Council and MS Research Australia with the full support of the Trish MS Research Foundation. He sets out to discover more detail on how the Vitamin D Receptor (VDR) can change immune cell function in MS. Specifically, he will be using a gene sequencing technology to better understand the function of key MS risk genes which are regulated by the Vitamin D receptor. Dr Ong will first study the relationship between the Vitamin D receptor activity and the growth and development of a particular type of messenger immune cells called dendritic cells.

Outcome

Dr Ong has made excellent progress on his research and has now completed the gene sequencing experiments which will allow him to determine the way that vitamin D effects genes within the immune cells using DNA methylation. DNA methylation one way that the activity of genes can be switched on or off in cells and Dr Ong is testing to see whether vitamin D may be able to effect the genes that are related to risk of developing MS. To do this, Dr Ong used a technique called modified reduced representation bisulfite sequencing that allowed him to analyse the methylation at all the genes present in the genome at once. As part of this work, Dr Ong also developed and optimised a bioinformatics pipeline specifically for this research project. This work may explain one mechanism whereby vitamin D affects the risk of developing MS through modulation of MS risk genes. In new work, Dr Ong has shown that the methylation signature in the cells is transmitted from stem cells to daughter cells. This forms a potential pathway by which environmental exposure to Vitamin D affects the risk of MS. The methylation maps that Dr Ong has generated for these cells will also serve as a resource for the scientific community to be analysed and compared with other methylation patterns from individuals with disease and also those subject to specific environmental exposures. Dr Ong is presenting this research at the European Academy of Allergy and Clinical Immunology in May 2018. As the peak body for clinical immunology in Europe, this congress brings together Clinical Immunologists and Immunology researchers from around the world. Updated: 31 March 2019

lead investigator

  • Dr Lawrence Ong, The Westmead Institute for Medical Research, NSW

supervisor

total funding

$122,714

start year

2016

duration

3 years over 2016 - 2018

STATUS

Past project

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The role of Vitamin D related genes in MS