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Position Summary:
Does in vitro and in vivo signalling bias translate into differences between the behavioral effects of distinctly biased agonists? This question will be explored in the context of the 5-HT2A receptor.
We will initially test a general category of psychedelics with LSD, DMT, 5-MeO-DMT, and psilocin (for the pro-drug psilocybin), each acting as an agonist at the 5-HT2A receptor. Structurally, all of these possess tryptamine backbones. Despite this commonality, it remains to be seen whether they all activate 5-HT2A receptors in the same manner, that is, whether they all activate the same G protein or b-arrestin partners. Exceptions to this description includes two highly selective 5-HT2A phenethylamines: DOI, an agonist acting as a psychedelic and MDL100907, an antagonist, which as such might serve as a useful research tool, and lisuride which is structurally related to LSD and generates 5-HT2A receptor activation but lacks the associated behavioral effects suggesting key differences with respect to engagement of second messenger systems. Duties include:
Profiling of multiple compounds in HEK 293 cells and primary neurons
Generating SOPs to monitor signaling and functional selectivity of target GPCRs
in primary neurons
Generating signaling signatures at single cell resolution for selected GPCRs in
different physiological settings.
Profiling and behavioural correlates in rat models
Training undergraduate and graduate students.
Preparing publications that emerge from this work.
Education/Experience:
PhD with five years of postdoctoral experience. Direct experience in the GPCR field, both in vitro and in vivo use of biosensors. Experience with viral versions of FRET-based biosensors of PKA and ERK to assess signalling profiles of active and interesting compounds in primary neurons.
Experience with a broad panel of FRET-based biosensors would be used in HEK 293 primary neurons to examine differential G protein coupling, β-arrestin recruitment and downstream protein kinase activation (PKC reflecting Gq activation, PKA- reflecting Gs and Gi activation, Src- reflecting b-arrestin.
Experience with high content imaging systems.
Other Qualifying Skills & Abilities:
Ability to teach and interact with trainees.
Knowledge of French and English: McGill University is an English-language university where day to day duties may require English communication both verbally and in writing. The level of English required for this position has been assessed at a level #4 (qualifier) on a scale of 0-4 .
Planned Start Date & End Date of appointment: April 15, 2024 – July 14, 2024
Work schedule is Monday to Friday (On-site) 35h/week.
The position is covered by the Association of McGill University Research Employees (AMURE) collective agreement.
Hourly Salary:
$32.79
Hours per Week:
35 (Full time)
Location:
McIntyre Medical
Supervisor:
Professor
Position Start Date:
2024-04-02
Position End Date:
2024-07-14
Deadline to Apply:
2024-04-09
This position is covered by the Association of McGill University Research Employees (AMURE) collective agreement.
McGill University hires on the basis of merit and is strongly committed to equity and diversity within its community. We welcome applications from racialized persons/visible minorities, women, Indigenous persons, persons with disabilities, ethnic minorities, and persons of minority sexual orientations and gender identities, as well as from all qualified candidates with the skills and knowledge to productively engage with diverse communities. McGill implements an employment equity program and encourages members of designated groups to self-identify. Persons with disabilities who anticipate needing accommodations for any part of the application process may contact, in confidence, [email protected] .