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| The genetic regulation of interneuron development in the mammalian retina. | ||||||||||||
Mammalian eye development has long been an informative model for the determination of cell fate within the central nervous system (CNS), because of its relatively simple structure. Although eye development in different organisms produces dramatically different structures, like the compound eye of insects and the camera-like eye of vertebrates, the molecular mechanisms underlying eye specification are highly conserved, and the study of eye development in animal models has proven to be highly informative of the regulatory events that control human eye formation. For example, Pax6 was identified as a ‘master’ regulator, at the top of the hierarchical network of transcription factors (TFs) involved in eye development, since loss-of-function mutations of the eyeless gene (the Pax6 Drosophila homologue) lead to an eyeless phenotype, and over-expression can direct the formation of histologically normal ectopic eyes in flies and some mammals. In the adult mammalian eye, rod and cone photoreceptors, which detect light in the retina, transduce this signal to the major class of interneurons, bipolar cells, which relay the information to the optic nerve, and thereby, to the rest of the brain. Much recent interest has focused on inherited disorders of rod and cone development and maintenance, such as retinitis pigmentosa and Leber’s congenital amaurosis, since the advent of AAV-mediated gene delivery as a viable therapeutic modality for patients blinded by these disorders. In contrast, much less is known about the genetic regulation of bipolar cell development; yet many of the TFs that are important for bipolar cell development also regulate interneuron development elsewhere in the CNS, e.g. the spinal cord and brain. Consequently, lessons learnt from the retina may have wider application to other inherited neurological disorders; for example, human heterozygous PAX6 mutations lead to eye malformations, including aniridia, while homozygotes also demonstrate CNS malformations. The major aims of this project are to define the relationships between transcription factors that are known to regulate retinal interneuron development, and to further elucidate the molecular mechanisms that underpin development of the retina, using a number of imaging techniques, chromatin immunoprecipitation, real-time PCR and microarray technology. The PhD candidate will be based in the Academic Department of Ophthalmology, Clinical Sciences at South Bristol, in the Faculty of Medicine & Dentistry. They will benefit from the well-respected PhD training programme at the University of Bristol and access to state-of-the-art facilities in the School of Medical Sciences and Bristol Neuroscience. Applications are invited from suitably qualified graduates, 2:1 or above. How to apply Please send a CV and cover letter, including contact details for two academic referees, to Dr Denize Atan, email: Denize.Atan@bristol.ac.uk. Your covering letter should outline your academic interests, prior research experience and reasons for wishing to undertake this project. Closing date for applications: 2nd August 2010 Start date: 1st October 2010 For further information about the project, please contact Dr Denize Atan, email: Denize.Atan@bristol.ac.uk. For more information about studying at the University of Bristol, please visit: http://www.bristol.ac.uk/prospectus/postgraduate/2010/ Funding Notes A three-year studentship, including a stipend at the current research council rate and studentship fees, is available to residents of the UK/EU for at least three years. Candidates from countries outside the EU will be liable for the difference between ‘home student fees’ and ‘international student fees’. If you wish to be considered for this studentship, you must confirm that you are able to pay the international portion of the fee. |
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