Epigenetic signatures of MS: from brain to blood

Investigator

  • Ms Katherine Sanders, Bond University Queensland

Supervisor

  • Associate Professor Lotti Tajouri, Bond University Queensland
  • Associate Professor Jeannette Lechner-Scott, Hunter Medical Research Institute
  • Professor Rodney Scott, Hunter Medical Research Institute

Funding

Summary

microRNAs (miRNAs) are molecules that are used by cells to control gene activity by different cell types. Since the genome of each cell is identical, this is one of the mechanisms by which characteristics of individual cell types are controlled. miRNAs are known to play roles in cell growth, cell death and development of tissue types. miRNAs are also known to play a role in disease processes.

Ms Sanders will be investigating the profile of miRNAs in MS. Since miRNA function differs between cell types, she will look directly at the miRNA profile in MS lesions taken from the brain tissue of people with MS, something that has only been done in a limited capacity before. Since miRNA molecules are remarkably stable, there is great potential for them to be used as biomarkers to diagnose and predict disease outcome in MS.

This study will combine array data and miRNA sequencing to fully investigate miRNA dysregulation in MS and correlate these changes in circulating body fluids to identify potential biomarkers for diagnosis and potentially further elucidate mechanisms that underlie the disease process in MS.

Progress to Date

In the first stage of this project, Ms Sanders has looked at miRNA taken from specific immune cells of people with secondary progressive MS and compared them to healthy controls. Within these immune cells, Ms Sanders has identified several specific miRNAs that have altered activity in MS. This includes a number of miRNA that target a gene involved in regulating the immune system activity. This has not previously been identified in MS and is currently being written up for publication.

The second stage of the project is working to determine the miRNA signature within brain tissue from people with MS. This project has received tissue samples from the MS Research Australia Brain Bank, which shall be used for the miRNA profiling. These tissues are from secondary progressive MS individuals and therefore are able to be compared to the miRNA profiles Ms Sanders identified in immune cells. To profile the samples, Ms Sanders is using a novel method called NanoString technology. This technique employs fluorescent barcodes that very specifically tag particular miRNA. Microscope images are then taken of the sample and the exact number of molecules counted; thus giving very specific data whilst limiting the amount sample used – an important consideration for such precious brain tissue samples. During 2015 Ms Sanders generated miRNA profiles of normal-appearing white matter brain tissue using this technology, and in 2016 will be undertaking detailed analysis of these profiles. As part of these analyses, Ms Sanders will conduct experiments to determine the functional role of the miRNA that are dysregulated in MS.

Ms Sanders is preparing a manuscript to publish her earlier findings showing altered miRNA activity in immune cells, and during 2015 presented her findings at four international conferences.

Updated 12/04/2016