Mapping the spatial distribution of adhesion GPCR latrophilin-3 (ADGRL3) in the dopamine system
Supervisors:
Dr Nicole Perry-Hauser, School of Molecular Biosciences
Dr Mick Craig, School of Psychology & Neuroscience
Summary:
Dopamine is a critical neurotransmitter involved in motor control, motivation, and working memory, and disruptions in dopamine signalling are linked to neurodevelopmental and neuropsychiatric disorders. Genetic variants in Adgrl3 are associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) and substance use disorder, both of which involve dysregulation of the dopamine system. Animal studies suggest that Adgrl3 plays a role in modulating dopaminergic neurotransmission, but the mechanisms remain poorly understood.
In this project, the student will investigate how ADGRL3 contributes to the organisation of the dopamine system. Using newly developed synthetic antibodies, the student will map ADGRL3 expression in mouse brain tissue, combining immunohistochemistry with high-resolution confocal and Mesolens imaging to visualise receptor distribution in both thin and ultra-thick brain sections. Comparisons between wild-type and region-specific Adgrl3 knockout mice will be used to determine how loss of the receptor affects the structural integrity of dopamine circuits.
The student will gain hands-on training in a range of experimental techniques, including tissue preparation, microscopy, and antibody validation, alongside a strong theoretical foundation in neuroscience and imaging. They will also engage with a non-profit research partner in the United States to gain insight into translational antibody development. Regular supervisory meetings and tailored career development activities will further support the student’s progression. This multidisciplinary project will equip them with valuable skills for careers in academic, industrial, or non-profit research environments.