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Josef Kittler & Zheng Li Collaboration

Title: The function of DTNBP1 (a schizophrenia risk gene) in neural differentiation

UCL supervisor: Josef Kittler, Ph.D., Neuroscience, Physiology and Pharmacology
NIH supervisor: Zheng Li, Ph.D., Synapse Development and Plasticity, NIMH

Background

Schizophrenia is a debilitating mental illness caused by complex interactions between multiple genes and the environment. Linkage and association studies have led to the discovery of DTNBP1 as a gene confers risk for schizophrenia. DTNBP1 encodes the dysbindin protein which has three isoforms in human (A, B and C) and two in mouse (A and C). During brain development, the A isoform decreases, while the C isoform increases. The developmental changes in dysbindin expression suggest that dysbindin is involved in neuronal development. The A isoform has been found to regulate the maturation of dendritic spines in excitatory neurons. It remains to be determined whether or not dysbindin isoforms play roles in neuronal differentiation. We are also interested in the potential role of dysbindin for regulating formation or plasticity of inhibitory synapses and the possibility that dysbindin function could contribute to the regulation of the excitatory/ inhibitory balance of neurons.

Methods

At the Unit on Synapse Development and Plasticity, NIMH, the function of dysbindin in neural differentiation will be investigated using a variety of molecular, cell biological and electrophysiological approaches designed together by the PhD candidate and the supervisors. Complementary studies will be conducted at UCL, which will investigate the impact of dysbindin function on inhibitory synaptogenesis and the trafficking of inhibitory GABAA receptors and adhesion molecules including the Schizophrenia associated NLGN2. The consequences of altered dysbindin function on inhibitory synaptic transmission will also be investigated.

Contact details:
Josef Kittler, Ph.D. - j.kittler@ucl.ac.uk
Zheng Li, Ph.D. - lizheng2@mail.nih.gov