The University of Manchester
PhD Studentship
Zebrafish As A Model Organism To Study Lowe Syndrome
Faculty of Life Sciences
Dr Martin Lowe
Project to start September 2008
Lowe syndrome (LS) is an X-linked disorder affecting the brain, kidneys and eyes. It is caused by mutation of OCRL1, an inositol polyphosphate 5-phosphatase localised to the Golgi apparatus, endosomes and lamellipodia. OCRL1 appears to regulate actin dynamics and membrane traffic, but the mechanisms involved are poorly defined, and consequently we do not understand how loss of OCRL1 brings about the symptoms associated with LS. Progress in this area has been hampered by the lack of a model organism that recapitulates the syndrome pathology.
This project aims to utilise zebrafish (Danio rerio) as a model to investigate the role of OCRL1 in development, and to gain insight into how loss of the protein brings about the defects associated with LS. During the first part of the project ablation of OCRL1 by morpholino injection and over-expression of exogenous OCRL constructs will be performed, and the phenotypic consequences of these manipulations during early embryogenesis studied, focussing on the developing brain and kidney.
A variety of modern microscopy and molecular techniques will be used for this purpose.
The analysis will be then be expanded by obtaining zebrafish containing mutant OCRL1 alleles. This will permit a detailed investigation of the role of OCRL1 during both early and later stages of development, and hopefully serve as a valuable model for future screening of potential therapeutics.
For more details about this project please contact Dr Martin Lowe (martin.p.lowe@ manchester. ac.uk ) or the Faculty of Life Sciences Graduate Office (Email: pg.lifesciences@ manchester. ac.uk , Tel: 0161 275 5608)
This studentship is available to applicants from all nationalities.
Applicants will need a UK upper second class or first class honours degree (or overseas equivalent).
Full details of how to apply can be found at:
www.manchester. ac.uk/lifescienc es/postgraduate/ apply/
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