Dr Natasha Grimsey
Applications accepted all year round
Competition Funded PhD Project (Students Worldwide)
About the Project
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). Both receptors are under intense scrutiny as potential therapeutic targets.
CB2 is expressed primarily in the immune system and CB2-targeted drugs are promising therapeutic leads in a wide range of disorders involving immune system dysregulation, including multiple sclerosis, autoimmune disorders, atherosclerosis, stroke and inflammatory bowel disease.
We are particularly interested in studying functional selectivity, wherein a single GPCR has the potential to mediate the activation or inactivation of diverse signalling pathways and each molecule that interacts with the receptor has the potential to induce a unique ‘fingerprint’ of signalling events within the cell. An emerging concept in functional selectivity is that of spatio-temporal modulation, and this project will characterise ligand function in this context by utilising cutting-edge spatially restricted signalling pathway biosensors.
This project will investigate these aspects of CB2 signalling and function from a variety of aspects, including investigating the influences of spatial and temporal signalling bias on CB2 function in primary human immune cells. As well, we collaborate with medicinal chemists who generate new cannabinoid compounds with potential for generating signalling and/or spatial bias which will be investigated and have potential to be developed into novel therapeutic leads.
Skills Taught (background / working knowledge on application advantageous)
• Mammalian cell culture and transfection
• GPCR signalling assays, e.g. cAMP, pERK, intracellular calcium, beta-arrestin, intracellular trafficking
• Biosensor assays utilising resonance energy transfer (RET) technologies
• Immune cell functional assays
• Molecular biology / cloning
Funding Notes
Competitive scholarship funding is available; applicants will need a suitable qualifying degree in a related subject area with a strong GPA/E to be considered.
Enquiries are invited from prospective PhD candidates with excellent grades from their entry qualification.
A background in the molecular pharmacology of GPCRs and/or immunology is strongly preferred.
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