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Download APPLICATION FOR MRC STUDENTSHIPS TO COMMENCE 2009
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PhD Project Title: Embryonic stem cell models of neurodevelopmental disorders Supervisors: Dr Lia Panman and Professor Giovanna Mallucci Aims: This studentship will investigate how dopamine neurons are specified during development and how its dysfunction is associated with neurodevelopmental disorders including ADHD and Schizophrenia. The study will focus on the function of a transcription factor in the specification and function of a group of dopamine neurons using mice and embryonic stem (ES) cell models. We will direct the differentiation of ES cells towards dopamine neurons to model neurodevelopmental disorders in vitro. Background: Dopamine neurons are a highly diverse neuronal population controlling important brain functions, such as motor action, cognition, motivation, reward and emotions. Dopamine neurons can be broadly subdivided into three groups, which form the substantia nigra (SN), ventral tegmental area (VTA) and the retrorubral field (RRF). SN dopamine neurons innervate the dorsal/lateral part of the striatum and control motor action, while VTA neurons regulate mesolimbic and mesocortical pathways. The different subpopulations of dopamine neurons are associated with distinct diseases. The selective degeneration of SN dopamine neurons causes the movement impairments in Parkinson’s disease. The dysfunction of VTA neurons has been associated with several neurological disorders including ADHD, anxiety, schizophrenia and autism and often these disorders originate during embryonic development. We have recently identified several transcription factors that are exclusively expressed in either SN or VTA dopamine neurons. One of the identified transcription factors is selectively expressed in VTA dopamine neurons already during early embryonic development. We would like to study the role of this gene in the specification and function of this subpopulation of dopamine neurons. In addition, we would like to use embryonic stem cells to model neurodevelopmental disorders that are caused by dysfunction of VTA dopamine neurons. Training Objectives: This is a multidisciplinary project and will make use of different model systems. The student will gain experience in working with embryonic stem cells and mice and use a number of techniques including fluorescence imaging, electrophysiology and RNA sequencing. Furthermore, the student will use embryonic stem cell differentiation protocols to model diseases in vitro. The University of Leicester runs a variety of training modules and courses that the student will be encouraged to attend. In the unit, the student will follow weekly external and internal seminar programs and will be encouraged to attend the postdoc/student forums which run each month.