Niemann-Pick type C disease: pathogenesis and therapy

SPHINGONET-ESR9

Project description
Our working hypothesis is that the NPC1 protein that is deficient in most cases of Niemann-Pick disease type C (NPC) plays a direct/indirect role in sphingoid base efflux from lysosomes. The yeast system will be exploited to probe the role of NPC1 in regulating sphingoid base metabolism. Genetic screens will be used to identify yeast and mammalian sphingoid base transporters. We will exploit the photoactivatable Sph analogues to measure binding to NPC1 and use the peptide reagents to measure changes in Sph/S1P levels in NPC1 null cells. Novel therapeutic approaches based on sphingosine metabolism will be evaluated in NPC patient cells and in a mouse model of NPC1 disease.

Further reading
Lloyd-Evans, E. et al. (2008) Nature Medicine 14, 1247-1255
Lloyd-Evans, E. and Platt, F.M. (2010) Traffic 11, 419-428
Morgan, A., et al. (2011) Biochem. J. 439, 349-374

Host institute
Department of Pharmacology
University of Oxford
Mansfield Road, Oxford, UK
Supervisor: Prof. Fran Platt
E-mail: frances.platt@pharm.ox.ac.uk
Phone: +49(0) 1865 271858
Web: http://plattlab.nsms.ox.ac.uk/

The Pharmacology Department is part of the Medical Sciences Division within the University of Oxford. The Departmental building is located in the center of the historic City of Oxford. Areas of research in the Department include molecular pharmacology, cardiac pharmacology, neuropharmacology, cell signaling, pharmacogenetics, lysosomal cell biology and lysosomal disorders. The research of the Department has consistently been given a very high ranking in the Government’s assessments of research in Universities. The department is well equipped for microscopy/imaging, flow cytometry and in vivo pharmacology.

Requirements
•  An undergraduate degree (minimum 2.1 equivalent grade) in biochemistry, cell biology or a related discipline would be desirable.
•  Proactive participation in SPHINGONET’s research & training program is expected through presentations and critical thinking at internal scientific forums, requiring excellent English presentation and writing skills. Strong communication skills and the ability to work in a team are a must.
•  Candidates must fulfill the eligibility criteria for Marie Curie Initial Training Networks (FP7).
•  Candidates should submit the complete application package.
•  Suitable candidates will be invited for an interview by the supervisor of the project.

Appointment
•  PhD student for 3 years.
•  Full-time.