School of Medical Sciences


Neuroimmune Interactions Research Group

Research interests


Mission - My particular research interests envelope the interactions occurring between the brain and immune system, including events that may exacerbate brain injury. Our brains are bombarded throughout our lives by colds, infections, alcohol, drugs and a series of minor traumatic events such as bumps or sports injuries. All of these will have an impact on brain function and we are interested in the events that culminate in influencing the viability and function of the brain’s resident immune cells (e.g. the microglia, astrocytes and endothelial cells). The health of these cells is critical to neuronal function and neurotransmission.

I have a particular interest in the cannabinoid system and the potential of the CB2 receptor as an anti-inflammatory target for neurological diseases. From rodent models, CB2 drugs have shown considerable promise in models of stroke and multiple sclerosis. Previously my research provided the first definitive profile of CB2 receptor localisation using flow-cytometry by human circulating immune cells. Currently we are investigating the expression and function of the CB2 receptor in the human brain and influence it has over immune cells bearing CB2 in humans.

Another area of interest is the development of cutting-edge technologies to advance our understanding of neuroscience. In collaboaration with Dr Charles Unsworth (Engineering) we are in the process of developing.

Approach - My research predominantly uses human tissue, cells or well-validated human cell lines.

Researchers


  • Dr Jessica Costa (research fellow)
  • Anower Jabed (assistant)
  • Christa Van Kralingen (technician)

Current students


  • Alireza Javaremi (PhD candidate)

Graduated students


  • Dr Natasha Grimsey (PhD)
  • Dr Emma Scotter (PhD)
  • Matt Slabbert (MSc)
  • Sheryl Tan (BSc)
  • Candy Wu (BSc)

Collaborations


  • Assoc. Prof. Michelle Glass (CB2 and Immune cells)
  • Dr Kate Angel (Immunology)
  • Prof Mike Dragunow (Brain Glial Cells)
  • Dr Juha Savinainen (University of Kuopio, Finland)
  • Dr Charles Unsworth (Neuroengineering Research)

Technologies


  • xCELLigence system-live cell biosensor (see http://www.roche-applied-science.com/sis/xcelligence/ezhome.html )
  • Olympus live cell imaging platform
  • Blood work and isolation of immune cells
  • Immunohistochemistry, cytochemistry and In Situ Hybridisation
  • Flow-cytometry and cytokine measurements
  • HTS assay development for cell-viability/death

Recent publications selected from 2006


Peer reviewed publications

  1. Natasha L Grimsey, Kriebashne Moodley, Michelle Glass, E Scott Graham (2011). Sensitive and accurate quantification of human leukocyte migration using high-content Discovery-1 imaging system and ATPlite assay. J Biomol Screen, 17(3), 386-393. doi:10.1177/1087057111428985. 2011.
  2. Kristina Burkert, Kiebashne Moodley, Catherine E Angel, Anna Brooks, E Scott Graham (2011). Detailed analysis of inflammatory and neuromodulatory cytokine secretion from human NT2 astrocytes using multiplex bead array. Neurochem Int. doi:10.1016/j.neuint.2011.09.002.
  3. Unsworth C, Graham ES, Delivopoulos E, Murray AF. Human hNT (2011). Astrocytes Patterned to Single Cell Resolution on Parylene-C/Silicon Dioxide Substrates. Bioreactivity Effects of Living Cells IEEE EMBC Conference Full paper; August 2011.
  4. Moodley K, Angel CE, Glass M, Graham ES (2011). Real-time profiling of NK cell killing of human astrocytes using xCELLigence technology. Neurosci Methods. 2011 Jul 18. [Epub ahead of print] (http://www.ncbi.nlm.nih.gov/pubmed/21781988).
  5. Unsworth C, Holloway H, Delivopoulos E, Murray F, Simpson C, Dickinson M, ES Graham (2011) Patterning and detailed study of human hNT astrocytes on parylene-C/silicon dioxide substrates to the single cell level. Biomaterials, 32 (27), Sept 2011, P6541-6550. [Epub ahead of Print].
  6. Goodfellow CE, Graham ES, Dragunow M, Glass, M (2011). Characterisation of NTera2/D1 cells as a model system for the investigation of cannabinoid function in human neurons and astrocytes. J Neurosci Res; published Jun 14 2011. doi: 10.1002/jnr.22692. [Epub ahead of print].
  7. Unsworth C. F.; Graham ES.; Delivopoulos E, Murray F (2010). First human hNT neurons patterned on parylene-C/silicon dioxide substrates: Combining an accessible cell line and robust patterning technology for the study of the pathological adult human brain. J Neurosci Meth 194, p154-157 22 DEC 2010.
  8. Grimsey NL, Graham ES, Dragunow M and M Glass (2010). Cannabinoid Receptor 1 Trafficking and the Role of the Intracellular Pool: Implications for Therapeutics. Biochemical Pharmacology. 2010 Jun 23. [Epub ahead of print]. PMID: 20599795.
  9. Scotter EL, Goodfellow CE, Graham ES, Dragunow M and M Glass (2010). Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington’s disease. British Journal of Pharmacology, 160, p747–761.
  10. Graham ES, Angel CE, Schwarcz L, Dunbar PR and Glass M (2010). Detailed characterisation of CB2 receptor protein expression in peripheral blood immune cells from healthy human volunteers using flow cytometry. Int J Immunopath Pharmacol, 3 (1): p25-34.
  11. Scotter, EL, Graham ES and Glass M. (2009) Signal transduction of CB1 receptors. In “Cannabinoids: Structure and Function” Ed. P. Reggio. Humana Press.
  12. Graham ES, Ashton JC, Glass M. Cannabinoid Receptors: A brief history and “what’s hot”. FRONTIERS IN BIOSCIENCE. 14, p944-957, 2008.
  13. Grimsey N, Goodfellow CG, Scotter EL, Dowie M, Glass M and Graham ES. Specific detection of CB1 receptors; cannabinoid CB1 receptor antibodies are not all created equal. J. Neurosci. Meth. 171 (1): p78-86, Mar 2008.
  14. Graham ES, Ball N, Scotter EL, Narayan PJ, Dragunow M, Glass M. Induction of Krox-24 by endogenous cannabinoid type 1 receptors in Neuro2A cells is mediated by the MEK-ERK MAPK pathway and is suppressed by the phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 281 (39): p29085-29095, 2006.
  15. Barrett P, Ivanova E, Graham ES, Ross AW, Wilson D, Ple H, Mercer JG, et al. Photoperiodic regulation of cellular retinoic acid-binding protein 1, GPR50 and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster. J. Endocrinol. 191(3): p687-98, 2006.