Theme Leads
Research Focus
This Theme is dedicated to identifying and validating new drug targets for psychiatric disorders. It does so by using the latest discoveries in genetics and brain sciences that are revealing the biological processes underlying the disorders. This paves the way to develop more precise and effective interventions, in contrast to current treatments which only treat the symptoms, are of limited effectiveness, and have many side-effects.
Regional Context
The work is based at the University of Oxford in the Department of Psychiatry and the Centre for Human Genetics. It also includes researchers in other Oxford Departments, as well as researchers at the University of Birmingham and clinicians at Oxford Health and Birmingham Women’s and Children’s NHS Foundation Trusts. The Theme therefore benefits from multi-institutional and multi-disciplinary collaborations, with access to diverse clinical populations, advanced laboratory infrastructure, and a broad spectrum of scientific expertise. Our PPIEP group, called MoTAG, is similarly diverse.
Research Aims
The Theme is structured around two complementary work packages (WPs), each designed to address key challenges in psychiatric drug development:
- WP1: Translating Genomic Discoveries into Therapeutic Targets
We have established a pipeline for converting genetic and other molecular discoveries into viable drug targets. A major focus is on voltage-gated calcium channels (VGCCs), since these play critical roles in brain cells and are part of the cause of conditions such as schizophrenia and bipolar disorder. Other molecular targets of interest are also being studied. To make progress, we use cutting-edge laboratory techniques and combine these with state-of-the-art computational methods to analyse the data.
- WP2: Back-Translation of Biomarkers in First-Episode Psychosis
This work package starts with findings in, and blood samples from, patients with early-stage schizophrenia. It uses them to identify molecules that either cause or accompany the illness, and which could be treatment targets. In particular, we are interested in the role that antibodies against proteins in the brain may play in some patients’ illnesses. We also study the potential contribution of brain inflammation. As in WP1, we use the latest methods, including immunological techniques and stem cells, to achieve our goals. As part of this work we have also facilitated the integration of neurologists into psychiatric care, and promote recruitment into clinical trials between Oxford and Birmingham.
Impact
Several impacts are emerging from this Theme. First, we have identified new and specific forms of VGCCs in the human brain, which have the potential to be selectively targeted by drugs. Second, in work widely reported in the media, we have shown that some vaccines reduce the risk of dementia and we are now investigating the biological mechanisms involved. Third, we have built research capacity in ‘molecular psychiatry’, fostering interdisciplinary expertise, and promoting psychiatry as a dynamic and impactful career path for clinical and non-clinical researchers interested in this emerging field. Finally, our PPIEP group is pioneering how PPIEP can be adapted and applied to laboratory and molecular science – an area which is outside the usual remit of PPIEP in mental health.
