Reduced expression of the serotonin transporter impacts mitochondria in a sexually dimorphic manner.

Neuropsychiatric and neurodevelopmental disorders are complex conditions that arise from a variety of interacting genetic and environmental factors. Among these factors, altered serotonergic signalling and mitochondrial dysfunction are strongly implicated, with a growing body of evidence to suggesting that serotonergic signalling is an important regulator of mitochondrial biogenesis. The serotonin transporter (SERT) functions to regulate synaptic 5-HT, and human allelic variants of the serotonin reuptake transporter-linked polymorphic region (5-HTTLPR) are associated with reduced SERT expression and increased susceptibility for developing neuropsychiatric disorders.

The role of the dopamine D1 receptor in anticipatory pleasure and social play.

Social play is a highly rewarding activity seen across mammalian species that is vital for neurobehavioural development. Dysfunctions in social play are seen across psychiatric and neurodevelopmental disorders positing the importance of understanding the neurobiological mechanisms underlying social play. A multitude of neurotransmitter systems have been implicated in social play, with the present study focused on the role of dopamine, specifically the dopamine D1 receptor.

The effect of mixed tobacco monoamine oxidase inhibitors in animal models relevant to tobacco dependence.

Rationale: Tobacco monoamine oxidase (MAO) inhibitors have long been suspected of influencing tobacco dependence, but direct evidence of their effects has been difficult to obtain. Recently we have identified two new groups of monoamine oxidase inhibitors, hydroquinones and polyunsaturated fatty acids (linoleic and linolenic acid), abundant in tobacco smoke.

Objectives: To test, in relevant animal models, whether the combined effect of these inhibitors is sufficient to affect addictive responses to nicotine.

Development of DuoMYC: a synthetic cell penetrant miniprotein that efficiently inhibits the oncogenic transcription factor MYC.

The master regulator transcription factor MYC is implicated in numerous human cancers, and its targeting is a long-standing challenge in drug development. MYC is a typical 'undruggable' target, with no binding pockets on its DNA binding domain and extensive intrinsically disordered regions. Rather than trying to target MYC directly with classical modalities, here we engineer synthetic miniproteins that can bind to MYC's target DNA, the enhancer box (E-Box), and potently inhibit MYC-driven transcription.

Synthetic Peptides: Promising Modalities for the Targeting of Disease-Related Nucleic Acids.

DNA and RNA play pivotal roles in life processes by storing and transferring genetic information, modulating gene expression, and contributing to essential cellular machinery such as ribosomes. Dysregulation and mutations in nucleic acid-related processes are implicated in numerous diseases. Despite the critical impact on health of nucleic acid mutations or dysregulation, therapeutic compounds addressing these biomolecules remain limited.