Download APPLICATION FOR MRC STUDENTSHIPS TO COMMENCE 2009

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.