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Department of Pharmacology

 

Supervisors: Dr Paul Miller and Prof Amy Milton

Research area: Mental Health: addressing problems which may have a bearing on mental health, diseases, or disorders

Funding: Pinsent Darwin/SBS DTP PhD studentship

 

Project Summary 

Research in the Miller lab (Department of Pharmacology) examines antibody modulators and protein toxin modulators against ion channels, especially against GABA-A receptors (e.g. see https://www.nature.com/articles/s41586-022-04402-z). GABA-A receptors are the principal mediators of inhibitory neurotransmission in the central nervous system (CNS). Small molecule positive allosteric modulators (PAMs) such as benzodiazepines treat generalized anxiety disorder. Different subtypes of GABA-A receptor are involved in addiction, anxiety, cognition and depression. Unfortunately, lack of selectivity limits drug potential. The Miller lab has identified selective efficacious antibody PAMs instead, and has developed a shuttle system to transport antibodies from the bloodstream across the blood brain barrier (BBB) into the central nervous system (CNS). 

This project is interdisciplinary involving antibody production and characterisation in the Miller lab alongside animal behavioural tests of fear and anxiety in the Milton lab (Department of Psychology), e.g. see https://pubmed.ncbi.nlm.nih.gov/36266512/. The effects of applying a systemic shuttle delivery system into the CNS versus direct intracerebral administration of the antibodies to the amygdala and/or hippocampus will be compared in the Milton lab. The ability to test out more “fine-grained” pharmacological tools will reveal new subtype contributions of GABA-A receptors to mental health disorders, evaluate delivery systems for treatment, and pave the way for future antibody therapeutic development. 

Please contact the supervisor to express interest: Dr Paul Miller (pm676@cam.ac.uk) or Prof Amy Milton (alm46@cam.ac.uk).