Protein monoaminylation in the brain: novel mechanisms of neural development, plasticity, and disease

Human neurological disorders associated with monoaminergic (e.g., serotonin, norepinephrine, dopamine) dysfunction affect millions of individuals worldwide; however, treatments for these neurodevelopmental, neurodegenerative, and/or psychiatric disorders remain inadequate. Employing a unique combination of biochemical, molecular, and behavioural approaches, the maze lab is examining novel, neurotransmission independent roles for monoamines in the brain in the direct regulation of neural gene expression and synaptic plasticity. These findings indicate that alterations in protein monoaminylations (i.e., the covalent addition of monoamines to substrate proteins) directly affect the functionalities of modified proteins, such as histone H3, to modulate neurodevelopmental and synaptic related events. Participants will gain comprehensive insights into how this work integrates expertise from multiple disciplines (ranging from chromatin biochemistry to chemical biology, neuroepigenomics, and behavioural neuroscience) to fully characterize these evolutionarily conserved monoaminylation states in the central nervous system, as well as their potential roles in neurological disease. Participants will also gain unique perspectives into how these findings are being used to identify novel molecular mechanisms that promise to provide a unique platform for the generation of more effective pharmacotherapeutics.