Molecular Targets

Oxford and Birmingham

To identify and test new therapeutic targets for psychiatric disorders, utilising genomics and other fundamental discovery neuroscience

Current psychiatric drugs have many shortcomings including not being very effective, having side effects and treating the symptoms not the underlying disorder. These limitations contribute to poor outcomes and low quality of life.

Work in this Theme will exploit advances in genomics and other ‘-omics’ to find new therapeutic targets and study the molecular basis of psychiatric disorders.

Two related work packages will:

1) Create a pipeline for translating advances in genomics and other relevant discoveries into new drug targets (WP1)

2) Investigate and use immune (neuronal antibodies) and other biomarkers to ‘back translate’ novel targets in first-episode psychosis, and with the ultimate aim of developing immunological therapies (WP2)

WP1 will focus initially on voltage-gated calcium channels (VGCCs). VGCCs control the action of nerve cells and contribute to the risk of developing psychiatric disorders such as schizophrenia and bipolar disorder. It is known that VGCCs can be different in brain compared to other tissues, and in humans compared to other species. We want to explore these differences in detail, to understand better how VGCCs affect risk of psychiatric disorders and how they can be optimised as potential targets for future psychiatric treatments. The work will use novel molecular neuroscience and bioinformatics methods.  As the BRC proceeds, additional gene families will be selected for study using similar a rationale and approach.

WP2 will employ ‘back translation’ from clinical populations to identify novel causal factors and biomarkers for neuropsychiatric disorders. The focus is the role of anti-neuronal antibodies and inflammation in first episode schizophrenia and bipolar disorder to identify more rapid, targeted and innovative interventions. The work, a close collaboration between Oxford and Birmingham, will lead to harmonized clinics with a unified approach to diagnosis and management, facilitate the integration of neurology in to the clinic and employ new techniques to study the underlying pathophysiological mechanisms

PPIEP is embedded into the design, production and interpretation of the Theme. It will involve close work with Birmingham’s active 18-strong Youth Advisory Group, the Oxford Young Persons’ PPIEP group and the BRC’s core PPIEP activities.

 

This is a key fundamental goal with a commitment from all involved to finding ways to enhance the molecular skills of the research workforce. This will also include making psychiatry an attractive, relevant discipline offering significant career opportunities.