How do Multiple Sclerosis risk genes change immune cells

  • Project Lead

    Dr Melissa Gressle
    T: +61 3 83443 278
    E: mgresle@unimelb.edu.au
    Location: Department of Medicine, University of Melbourne, Royal Melbourne Hospital

Project Details

The causes of MS are unknown, but both genetic and environmental factors are known to increase the risk of MS. So far, more than 100 variations in our genetic blueprint have been found to occur more commonly in people with MS compared to unaffected individuals, but we do not know how these genetic variations work to cause disease.

In our preliminary studies, we have been able to show that several MS genetic risk variations change the levels of immune genes.  We are now trying to understand  how changes in the levels of these genes affect immune functions to increase the risk of developing MS.

Researchers

Collaborators

  • Judith Field, Florey Neuroscience Institute
  • Laura Johnson, Florey Neuroscience Institute
  • Alan Baxter, James Cook University
  • Margaret Jordan, James Cook University
  • Tim Spelman, Burnett Institute and University of Melbourne
  • MS Unit, Royal Melbourne Hospital
  • Eastern Clinical Research Unit, Box-Hill Hospital
  • David Booth, Westmead Millenium Institute

Funding

  • Gresle2015-2016Multiple Sclerosis Research Australia postdoctoral research fellowship
  • Butzkueven2015-2019NHMRC Practitioner fellowship
  • Butzkueven, Gresle2015Multiple Sclerosis Research Australia incubator grant
  • Vuong  2015    Multiple Sclerosis Research Australia summer studentship
  • Butzkueven2015Biogen Idec global commercial investigator initiated research support
  • Butzkueven2015Novartis IIT
  • Butzkueven, et al2012-2014NHMRC Project Grant
  • Butzkueven et al2011-2013ARC Linkage Grant

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Outcomes

  1. Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerveGresle MM, Liu Y, Kilpatrick TJ, Kemper  D, Wu QZ, Hu B, Fu QL, So KF, Sheng G,  Huang G, Pepinsky B, Butzkueven H and Mi S. Multiple Sclerosis Journal Experimental, Translational and Clinical 2016: 2: 1-13
  2. Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status.Binder MD, Fox AD, Merlo D, Johnson LJ, Giuffrida L, Calvert SE, Akkermann R, Ma GZ; ANZgene, Perera AA, Gresle MM, Laverick L, Foo G, Fabis-Pedrini MJ, Spelman T, Jordan MA, Baxter AG, Foote S, Butzkueven H, Kilpatrick TJ, Field J.PLoS Genet. 2016 Mar 18;12(3):e1005853.
  3. Field J, Shahijanian F, Schibeci S; Australia and New Zealand MS Genetics Consortium (ANZgene), Johnson L, Gresle M, Laverick L, Parnell G, Stewart G, McKay F, Kilpatrick T, Butzkueven H, Booth D. The MS Risk Allele of CD40 Is Associated with Reduced Cell Membrane Bound Expression in Antigen Presenting Cells: Implications for Gene Function. PLoS One. 2015 Jun 11;10(6):e0127080.

Research Publications

  1. A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis. Gu BJ, Field J, Dutertre S, Ou A, Kilpatrick T, Lechner-Scott J, Scott R, Lea R, Taylor BV, Stankovich J, Butzkueven H, Gresle M, Laws SM, Petrou S, Hoffjan S, Akkad DA, Graham CA, Hawkins S, Glaser A, Bedri SK, Hillert J, Matute C, Antiguedad A; ANZgene Consortium, Wiley JS. Hum Mol Genet. 2015 Jul 17. pii: ddv278. [Epub ahead of print]
  2. Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by Leukemia inhibitory Factor. Gresle MM  (equal contribution), Butzkueven H (equal contribution), Perreau VM, Jonas A, Thiem S, Holmes F, Doherty W, Soo PY, Binder M, Akkermann R, Jokubaitis V, Cate H, Marriott M, Xiao J, Gundlach A, Wynick D and Kilpatrick TJ. Glia. 2015 2015 Jun;63:1005-1020.  
  3. Axonally-derived matrillin-2 induces pro-inflammatory responses that exacerbate autoimmune neuroinflammation. Jonas A, Thiem S, Kuhlmann T, Wagener R, Aszodi A, Nowell C, Hagemeier K, Laverick L, Perreau VP, Jokubaitis VJ, Emery B, Kilpatrick TJ, Butzkueven H (equal contribution), Gresle M (equal contribution). Journal of Clinical Investigation. 2014;124:5042-5056.  
  4. Serum neurofilament-heavy chain levels in multiple sclerosis patients. Gresle MM, Liu Y, Dagley LF; Haartsen J, Pearson F; Purcell A; Laverick L, Petzold, A, Lucas RM; Van der Walt A, Prime H; Morris D; Taylor BV, on behalf of the Ausimmune Consortium; Shaw G, Butzkueven, H. J Neurol Neurosurg Psychiatry. 2014 Mar 17. doi: 10.1136/jnnp-2013-306789. [Epub ahead of print]
  5. Ceruloplasmin gene deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution. Gresle M; Schulz K; Jonas A; Perreau V; Cipriani T; Baxter A; Miranda-Hernandez S; Field J; Jokubiaits V; Cherny R; Volitakis I; David S; Kilpatrick TJ; and  Butzkueven H. J Neurosci Res. 2014;92:732-742.

Research Group

Multiple Sclerosis Outcomes and Prognostics Team



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology

Unit / Centre

Royal Melbourne Hospital