Novel cellular and animal models for schizophrenia and bipolar disorder

 

Supervisor(s):

 

Dr S Shen, Dr K Millar (Edinburgh) & Prof D Porteous (Edinburgh)

 

Funded by:

 

Scottish Universities Life Sciences Alliance

 

Eligibility:

 

Candidates should have (or expect to achieve) a First Class or 2.1 Honours degree (or equivalent) in a relevant subject.

 

Information

 

Schizophrenia and bipolar disorder are severe and common mental illnesses with no objective tests and limited treatment available. One problem in translational medicine is the lack of convincing cellular/animal models, to aid the development of biomarkers and to screen/validate effective drugs.

 

Schizophrenia and bipolar disorder are clinically and cytogenetically associated, with multiple genetic factors involved. The discovery of the DISC1 gene truncated in a Scottish schizophrenic family by co-supervisors KJM/DJP is a landmark of psychiatric genetics. The primary supervisor Shen has led genetic modelling of schizophrenia by expressing a truncated Disc1 gene in mice, which attracted 2 consecutive funding from TMRI/Wyeth as a model for schizophrenia.

 

We propose here to target a novel Disc1 binding partner called DBZ. DBZ is involved in cell proliferation and neurite outgrowth. The human DBZ gene is ~270 kb downstream of D10S609, a marker which has been linked with bipolar disorder, with no other genes in between. We will express full-length and dominant negative mutants of DBZ in PC12 cells, the most popular model system for neuronal differentiation. We will also generate DBZ null and dominant negative mutants of embryonic stem (ES) cells and mice. Characterisation of transfected PC12 cells and mutant ES cells on cell division and neuronal differentiation, may lead to cellular models of schizophrenia and bipolar disorder. We will analyse DBZ mutant mice at biochemical, cellular, anatomical and behavioural levels, as we have carried out for Disc1 mice, and they may become animal models for schizophrenia and bipolar disorder. We shall validate existing anti-psychotic drugs and antidepressants on cell lines and mutant mice. The project will enhance our understanding of cell biology of the DBZ, and it shall also lead to major grant proposals targeting pharmaceutical companies and research councils for full characterisation of the models and for screening/validation of novel drugs.

 

The research group offers training for both masters and PhD level in a range of areas that are summarised on the Theme web site). We invite applications from interested students and request that you contact the member of staff directly (sanbing.shen@abdn.ac.uk), but copy the e-mail to Fiona Insch (f.insch@abdn.ac.uk).