Mechanism of sphingolipid traffic at membrane contact sites

SPHINGONET-ESR6

Project description
This project stems from unpublished observations in the host laboratory that enhancing ER-Golgi contacts, potential hot-spots of sphingolipid traffic, is highly toxic to yeast. In this project, a chimeric ER-Golgi tether will be used to scan yeast deletion libraries to identify strains with altered sensitivity to the tether. Endogenous ER-Golgi contacts in wild-type and mutant strains with altered contact sites will be visualized with novel tags. Selected mutants will then be tested in depth for defects in (sphingo)-lipid biosynthesis and homeostasis, including studies of lipid transfer in vitro, and the proteome of contact sites. In addition, two families of novel candidate lipid transfer proteins recently identified in the host laboratory will be tested for their ability to transfer lipids, as one of these may a ceramide transfer protein at ER-Golgi contacts.

Further reading
Loewen and Levine T.P. (2006) Curr Opin Cell Biol. 18, 371-378
Loewen  et al. (2007) J Cell Biol 179, 467-483
Levine (2011) J. Cell Biol. 195, 927-929

Host institute
UCL, London, UK
Department of Cell Biology, Institute of Ophthalmology
Supervisor: Dr Tim Levine
E-mail: tim.levine@ucl.ac.uk
Web: http://www.ucl.ac.uk/ioo/pdf/PI/Dr%20Tim%20Levine.pdf

UCL is one of the top universities in the UK with a major focus on biomedicine. The Institute of Ophthalmology is one of the highest achieving institutes within UCL, with the highest possible ratings for research excellence. The Department of Cell Biology is well equipped, particularly with excellent imaging facilities for live cell microscopy and electron microscopy.

Requirements
•  We are looking for an ambitious, motivated and bright individual with a BSc degree or higher in molecular cell biology or biochemistry. Experience with microscopy, molecular biology and yeast genetics would be an advantage.
•  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.