Molecular Targets
Using advances in '-omics' and biomarkers to identify and validate psychiatric targets
Theme Leads
Main location of work
Theme overview
Why the work is important
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.
Aims
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)
What work will be carried out
WP1 will focus on functional and pharmacological characterisation of brain-specific voltage-gated calcium channels (VGCCs) to design channel modifying drugs (CCBs) that selectively target brain VGCCs without causing cardiovascular side effects. VGCCs control the action of nerve cells and contribute to the significant inherited risk of developing psychiatric disorders such as schizophrenia, bipolar disorder and depression so are an attractive drug target. This work will draw on expertise in genomic medicine, bioinformatics and involve collaborators focusing on drug discovery who can develop tools and lead compounds. Human brain tissue and induced pluripotent stem cells (iPSCs) will be used.
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
Patient and public involvement, engagement and participation
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.
For more information on PPIEP please contact: alexandra.almeida@psych.ox.ac.uk
Increasing research capacity and critical mass
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.