SLMS Academic Careers Office

4. Development of a Novel In Vivo Animal Model for Schizophrenia Drug Testing

Supervisor Pair: Dr Jennifer Linden & Professor Peter Scambler
Potential Student’s Home Department: Ear Institute
Schizophrenia afflicts 1% of the population worldwide, and extracts a huge toll not only on patients but also on their families and communities.  Currently available treatments for schizophrenia may alleviate positive and negative symptoms such as psychosis and anhedonia, but do not correct the pervasive cognitive deficits that are most predictive of adverse long-term outcomes.  These cognitive deficits are thought to arise from fundamental abnormalities in neocortical circuitry, which make the activity of cortical projection neurons more variable.  The aim of this Grand Challenge Studentship project is to develop a novel method for testing the potential of new drugs for cognitive deficits in schizophrenia, using a mouse model of human genetic risk for schizophrenia – the Df1/+ mouse model of human 22q11 Deletion Syndrome (22q11DS). 
In humans, 22q11DS is one of the most significant known genetic risk factors for schizophrenia, exceeded only by the risk factor associated with having a schizophrenic identical twin.  The Df1/+ mouse, which was genetically engineered to model human 22q11DS, recapitulates many features of the human syndrome, including cognitive and behavioural abnormalities associated with schizophrenia.  However, the Df1/+ mouse has never been used as model system for evaluating treatments for cognitive deficits in schizophrenia. 
This Grand Challenge Studentship project will leverage an interdisciplinary collaboration between experts in schizophrenia genetics, in vivo electrophysiology, and drug development, to achieve two specific aims: 
(1) development of an in vivo assay of cortical activity and sensory discrimination behaviour in awake Df1/+ mice (and their WT littermates), and 
(2) the use of this model system to measure the effects of novel pharmaceutical compounds on cortical activity and behavioural performance. 
The novel compounds will be provided by the industrial partner Autifony Therapeutics, a spin-off from GlaxoSmithKline R&D focused on drug development for schizophrenia, tinnitus and hearing loss.  This project will therefore contribute not only to basic research on cortical processing abnormalities associated with high genetic risk of schizophrenia, but also to translational efforts to develop novel treatments for currently intractable symptoms of schizophrenia.