Dr Natasha Lillia Grimsey

PhD Pharmacology, BCom/BSc(Hons)

Biography

Dr Natasha Grimsey leads the G Protein-Coupled Receptor (GPCR) Molecular Pharmacology lab in the Department of Pharmacology and Centre for Brain Research.

She is a University of Auckland graduate (BSc/BCom Hons Biomedical Science, PhD Pharmacology 2010) and has been mentored by eminent molecular pharmacologist Professor Michelle Glass.

A past Auckland Medical Research Foundation Edith C. Coan Fellowship recipient, Dr Grimsey is currently supported by two prestigious grants, a Marsden “FastStart” project grant and a Health Research Council Emerging Researcher First Grant.

Natasha's research focuses on GPCR signalling and intracellular trafficking, with emphasis on the cannabinoid receptors and how these influence normal physiology and disease, as well as the development of quantitative assays utilising high-throughput techniques.

Research | Current

The G Protein-Coupled Receptor (GPCR) Molecular Pharmacology lab is interested in the fundamental mechanisms of GPCR function, both in normal and disease states, and how these fascinating proteins might be harnessed for therapeutic gain.

Our current focus is on Cannabinoid Receptor 2 (CB2). This is one of the receptors for the active components of Cannabis, however does not mediate the psychotropic effects of Cannabis. Rather, this receptor is primarily found in immune cells and thought to mediate immunosuppression. It is therefore hoped that targeting CB2 might be therapeutically useful in a wide range of disorders, including neuroinflammation (e.g. stroke, neurodegeneration), auto-immunity (e.g. multiple sclerosis), atherosclerosis, and various cancers. However, study of this receptor is in its infancy in comparison with many other GPCRs and there is still much to be learned about how this receptor functions at a fundamental level.

Current lines of inquiry include:

  • Learning more about CB2 function via the design and study of novel potential therapeutic drugs with potential to activate or inhibit specific signals via CB2 and/or target different populations of CB2, in collaboration with Dr Andrea Vernall (University of Otago).
  • Investigating CB2 signalling and functional effects in primary human immune cells, in collaboration with Dr Scott Graham (Centre for Brain Research, University of Auckland).
  • Determining how the subcellular distribution of CB2 is controlled, including the protein-protein interactions responsible (which might in themselves represent novel therapeutic targets), in collaboration with Dr Darren Saunders (University of New South Wales, Australia).
  • Comparison of CB2 function in different species, which assists in defining the molecular mechanisms of human CB2 function and is particularly important for validation of preclinical models.

Techniques include: mammalian cell culture, radioligand binding, signalling assays (lysate and real-time RET biosensors), immunocytochemistry, widefield and confocal microscopy, high-throughput/content imaging and analysis, western blotting, bimolecular fluorescence complementation.

Publications

Teaching | Current

Lecturing:
- MEDSCI204 Pharmacology & Toxicology
- MEDSCI304 Molecular Pharmacology

Postgraduate supervision

Enquiries from prospective graduate students and postdocs are welcome.

Current

Caitlin Oyagawa (PhD primary supervisor)

Yurii Saroz (PhD primary supervisor)

David Finlay (PhD co-supervisor)

Monica Patel (Pharmacology honours co-supervisor)


Completed

Caitlin Oyagawa (2016, Masters primary supervisor)
Morag Hunter (2015, PhD co-supervisor)
Braden Woodhouse (2014, Honours primary supervisor)
David Finlay (2014, Masters co-supervisor)
Karan Govindpani (2014, Honours co-supervisor)
Summer students: Samuel King (2014), David Finlay (2013), AJ Sykes (2008)

Areas of expertise

  • Cannabinoids
  • Cannabinoid receptors 1 and 2 (CB1 & CB2)
  • G-protein coupled receptor trafficking and signalling
  • Receptor intracellular trafficking
  • Molecular pharmacology
  • Neuropharmacology
  • Signalling biosensors
  • High content analysis and high throughput screening

Selected publications and creative works (Research Outputs)

  • Finlay, D., Cawston, E., Grimsey, N., Hunter, M., Korde, A., Vemuri, V., ... Glass, M. (2017). Gαs signalling of the CB₁ receptor and the influence of receptor number. British Journal of Pharmacology, 174 (15), 2545-2562. 10.1111/bph.13866
    URL: http://hdl.handle.net/2292/35307
    Other University of Auckland co-authors: David Finlay, Michelle Glass, Erin Cawston
  • Hunter, M. R., Finlay, D. B., Macdonald, C. E., Cawston, E. E., Grimsey, N. L., & Glass, M. (2017). Real-time measurement of cannabinoid receptor-mediated cAMP signaling. Methods in Enzymology, 593, 43-59. 10.1016/bs.mie.2017.05.001
    Other University of Auckland co-authors: Michelle Glass, Erin Cawston, David Finlay
  • Finlay, D. B., Joseph, W. R., Grimsey, N. L., & Glass, M. (2016). GPR18 undergoes a high degree of constitutive trafficking but is unresponsive to N-Arachidonoyl Glycine. PeerJ, 410.7717/peerj.1835
    URL: http://hdl.handle.net/2292/30934
    Other University of Auckland co-authors: Michelle Glass, Wayne Joseph, David Finlay
  • Redmond, W. J., Cawston, E. E., Grimsey, N. L., Stuart, J., Edington, A. R., Glass, M., & Connor, M. (2016). Identification of N-arachidonoyl dopamine as a highly biased ligand at cannabinoid CB₁ receptors. British Journal of Pharmacology, 173 (1), 115-127. 10.1111/bph.13341
    Other University of Auckland co-authors: Erin Cawston, Michelle Glass
  • Dowie, M. J., Grimsey, N. L., Hoffman, T., Faull, R. L., & Glass, M. (2014). Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington's disease brain. Journal of Chemical Neuroanatomy, 59-60, 62-71. 10.1016/j.jchemneu.2014.06.004
    Other University of Auckland co-authors: Michelle Glass, Richard Faull
  • Cawston, E. E., Redmond, W. J., Breen, C. M., Grimsey, N. L., Connor, M., & Glass, M. (2013). Real-time characterization of cannabinoid receptor 1 (CB1 ) allosteric modulators reveals novel mechanism of action. Br J Pharmacol, 170 (4), 893-907. 10.1111/bph.12329
    Other University of Auckland co-authors: Michelle Glass, Erin Cawston
  • Hunter, M., Grimsey, N. L., & Glass, M. (1/1/2013). Constitutive heterodimerisation of cannabinoid CB1 and dopamine D2 receptors revealed using bioluminescence resonance energy transfer (BRET) assay. Poster presented at Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) New Zealand Annual Scientific Meeting., Queenstown, NZ. Related URL.
    Other University of Auckland co-authors: Michelle Glass
  • Grimsey, N. L., Moodley, K. S., Glass, M., & Graham, E. S. (2012). Sensitive and Accurate Quantification of Human Leukocyte Migration Using High-Content Discovery-1 Imaging System and ATPlite Assay. Journal of Biomolecular Screening, 17 (3), 386-393. 10.1177/1087057111428985
    URL: http://hdl.handle.net/2292/10482
    Other University of Auckland co-authors: Michelle Glass, Scott Graham, Kriebashne Moodley

Identifiers

Contact details

Primary office location

M&HS BUILDING 503 - Bldg 503
Level 5, Room 501
85 PARK RD
GRAFTON
AUCKLAND 1023
New Zealand

Social links

Web links