New Dimensions in Cannabinoid Receptor 2 Therapeutic Development [Multiple Projects]

Project Code: 10385612

Faculty: Faculty of Medical and Health Sciences

Department: Pharmacology

Main Supervisor: Dr Natasha Grimsey

Application open date: 16 Aug 2021

Application deadline:

Enrolment information: NZ Citizens, NZ Permanent Residents, International

Introduction

Compounds derived from Cannabis sativa, termed “cannabinoids”, primarily exert their effects via two G-protein coupled receptors (GPCRs), Cannabinoid Receptors 1 and 2 (CB1 and CB2). 

CB2 is expressed primarily in the immune system and the advent of CB2-selective ligands opens up exciting possibilities for therapeutic immune modulation without inducing adverse psychotropic effects which are typically mediated via CB1.  CB2-targeted drugs are therefore promising therapeutic leads in a wide range of disorders involving immune system dysregulation, including multiple sclerosis, autoimmune disorders, atherosclerosis, stroke and inflammatory bowel disease.

What we are looking for in a successful applicant

Enquiries are invited from students intending to commence their PhD, masters or honours studies.

A background in the molecular pharmacology of GPCRs and/or immunology is strongly preferred.

Objective

We are particularly interested in studying CB2 molecular pharmacology.  Specific projects will depend on our research focus at the time of application, and to some extent can be tailored to the interests and experience of the prospective student, however themes may include:

  • Development and characterisation of novel cannabinoid ligands
  • Generation of chimeras and site-directed-mutagenesis to probe the function of peptide residues and motifs in CB2
  • Investigating the impact of disease-linked non-synonymous CB2 single nucleotide polymorphisms
  • Functional selectivity of CB2 signalling in a spatio-temporal context utilising subcellularly targeted resonance energy transfer biosensors
  • Studying cannabinoid signalling and functional effects in human primary immune cells

Skills Taught

  • Mammalian cell culture and transfection
  • GPCR signalling assays: cAMP, pERK, intracellular calcium, beta-arrestin, intracellular trafficking
  • Biosensor assays utilising resonance energy transfer (RET) technologies
  • Human primary immune cell isolation and functional assays
  • Molecular biology: Cloning, site-directed mutagenesis, DNA preparation/purification, PCR
  • Immunocytochemistry
  • Automated fluorescence microscopy and quantitative image analysis
  • Ligand binding assays
  • Cytometric bead array

More about the Grimsey lab: https://unidirectory.auckland.ac.nz/profile/n-grimsey

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