Dr Tim Levine

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Name: Tim Levine Email: tim.levine@ucl.ac.uk
Title: Dr Tel:
Department: Inst Ophthalmology - Cell Biology Fax:
Position: Clinical Lecturer Address: Dept Cell Biol, UCL Institute of Ophthalmology, 11-43 Bath St, London, EC1V 9EL
Research Domain: Basic Life Sciences, Cardiometabolic Science, Neuroscience, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

We are working on the broad biological question of how lipids and proteins interact inside cells, using the budding yeast Saccharomyces cerevisae model system, which is genetically tractable. Understanding the regulation of lipid metabolism is of great medical importance for diseases prevalent in the Western world, including important ophthalmic diseases, such as AMD. The first of our main focus areas is lipid traffic across narrow cytoplasmic gaps (membrane contact sites) where organelles come very close to each other; in particular, VAP, a conserved protein that links the endoplasmic reticulum to other organelles. The second is phosphoinositide lipids as cellular signposts, especially in lens epithelial cells in relation to oculocerebrorenal syndrome of Lowe (OCRL), a rare and fatal disease that presents with bilateral congenital cataracts. By studying OCRL in the lens, we hope to generate ideas about treatment for the more clinically intractable problems in kidney and brain.

Research Activities

Intracellular Lipid Traffic

The Cell Biology of Eye Disease

Education Description

UCL Collaborators

Prof Clare Futter; Professor Francesca Cordeiro; Prof Karl Matter; Dr Darren Nesbeth; Prof Stephen Moss

External Collaborators

Publications

    2013

    • Levine TP, Menon AK (2013). A Protein Pair with PIPs Inside.. Structure, 21(7), 1070 - 1071. doi:10.1016/j.str.2013.06.010
    • Levine TP (2013). A Twoferase for Lipid Transfer at ER-Golgi Contact Sites.. Dev Cell, 27(4), 369 - 370. doi:10.1016/j.devcel.2013.11.009
    • Levine TP (2013). A Twoferase for Lipid Transfer at ER-Golgi Contact Sites. DEVELOPMENTAL CELL, 27(4), 369 - 370. doi:10.1016/j.devce1.2013.11.009
    • Alpy F, Rousseau A, Schwab Y, Legueux F, Stoll I, Wendling C, Spiegelhalter C, Kessler P, Mathelin C, Rio M-C, Levine TP, Tomasetto C (2013). STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER. JOURNAL OF CELL SCIENCE, 126(23), 5500 - 5512. doi:10.1242/jcs.139295
    • Levine TP, Daniels RD, Wong LH, Gatta AT, Gerondopoulos A, Barr FA (2013). Discovery of new Longin and Roadblock domains that form platforms for small GTPases in Ragulator and TRAPP-II.. Small GTPases, 4(2), 62 - 69. doi:10.4161/sgtp.24262
    • Levine TP, Daniels RD, Gatta AT, Wong LH, Hayes MJ (2013). The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.. Bioinformatics, 29(4), 499 - 503. doi:10.1093/bioinformatics/bts725
    • Chlystun M, Campanella M, Law AL, Duchen MR, Fatimathas L, Levine TP, Gerke V, Moss SE (2013). Regulation of mitochondrial morphogenesis by annexin A6.. PLoS One, 8(1), e53774 - . doi:10.1371/journal.pone.0053774

    2012

    • Mikitova V, Levine TP (2012). Analysis of the key elements of FFAT-like motifs identifies new proteins that potentially bind VAP on the ER, including two AKAPs and FAPP2.. PLoS One, 7(1), e30455 - . doi:10.1371/journal.pone.0030455

    2011

    • Grieve AG, Daniels RD, Sanchez-Heras E, Hayes MJ, Moss SE, Matter K, Lowe M, Levine TP (2011). Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells.. PLoS One, 6(8), e24044 - . doi:10.1371/journal.pone.0024044
    • Hayes MJ, Bryon K, Satkurunathan J, LEVINE TP (2011). Yeast homologues of three BLOC 1 subunits highlight KxDL proteins as conserved interactors of BLOC-1. Traffic, 12(3), 260 - 268.
    • Levine TP (2011). Lipid traffic: Osh4p makes an unexpected exchange.. J Cell Biol, 195(6), 927 - 929. doi:10.1083/jcb.201111074

    2009

    • Hayes MJ, Shao DM, Grieve A, Levine T, Bailly M, Moss SE (2009). Annexin A2 at the interface between F-actin and membranes enriched in phosphatidylinositol 4,5,-bisphosphate. Biochim.Biophys.Acta, 1793(6), 1086 - 1095.
    • Suzuki H, Kanekura K, Levine TP, Kohno K, Olkkonen VM, Aiso S, Matsuoka M (2009). ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes motor neurons to ER stress-related death by inducing aggregation of co-expressed wild-type VAPB. J.Neurochem., 108(4), 973 - 985.

    2008

    • Hayes MJ, Shao DM, Grieve A, Levine T, Bailly M, Moss SE (2008). Annexin A2 at the interface between F-actin and membranes enriched in phosphatidylinositol 4,5,-bisphosphate. Biochim.Biophys.Acta, , - .

    2007

    • Levine TP (2007). A lipid transfer protein that transfers lipid. J.Cell Biol., 179(1), 11 - 13.
    • Loewen CJR, Young BP, Tavassoli S, Levine TP (2007). Inheritance of cortical ER in yeast is required for normal septin organisation. The Journal of Cell Biology, 179(3), 467 - 483. doi:10.1083/jcb.200708205

    2006

    • Yeung T, Terebiznik M, Yu L, Silvius J, Abidi WM, Philips M, Levine T, Kapus A, Grinstein S (2006). Receptor activation alters inner surface potential during phagocytosis.. Science, 313(5785), 347 - 351. doi:10.1126/science.1129551
    • Loewen CJR, Levine TP (2006). Inter-organelle membrane contact sites: through a glass, darkly.. Curr Opin Cell Biol., 18, 371 - 378.

    2005

    • Holthuis JC, Levine TP (2005). Lipid traffic: floppy drives and a superhighway. NAT REV MOL CELL BIOL, 6(3), 209 - 220.
    • Levine T (2005). A new way for sterols to walk on water. MOL CELL, 19(6), 722 - 723.
    • Loewen CJ, Levine TP (2005). A highly conserved binding site in VAP for the FFAT motif of lipid binding proteins.. Journal of Biological Chemistry, 280, 14097 - 14104. doi:10.1074/jbc.M500147200
    • Levine T, Rabouille C (2005). Endoplasmic reticulum: one continuous network compartmentalized by extrinsic cues. CURR OPIN CELL BIOL, 17(4), 362 - 368.
    • Loewen CJ, Levine TP (2005). A highly conserved binding site in vesicle-associated membrane protein-associated protein (VAP) for the FFAT motif of lipid-binding proteins. J BIOL CHEM, 280(14), 14097 - 14104.

    2004

    • Levine T (2004). SSD: sterol-sensing direct.. Developmental Cell, 7(2), 152 - 153.
    • Levine T (2004). Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions.. Trends in cell biology, 14(9), 483 - 490. doi:10.1016/j.tcb.2004.07.017
    • Roy A, Levine TP (2004). Multiple pools of phosphatidylinositol 4-phosphate detected using the pleckstrin homology domain of Osh2p.. Journal of Biological Chemistry, 279(43), 44683 - 44689. doi:10.1074/jbc.M401583200
    • Loewen CJ, Gaspar ML, Jesch SA, Delon C, Ktistakis NT, Henry SA, Levine TP (2004). Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid.. Science, 304(5677), 1644 - 1647. doi:10.1126/science.1096083
    • Hayes MJ, Merrifield CJ, Shao D, Ayala-Sanmartin J, Schorey CD, Levine TP, Proust J, Curran J, Bailly M, Moss SE (2004). Annexin 2 binding to phosphatidylinositol 4,5-bisphosphate on endocytic vesicles is regulated by the stress response pathway.. Journal of Biological Chemistry, 279(14), 14157 - 14164.
    • Olkkonen VM, Levine TP (2004). Oxysterol binding proteins: in more than one place at one time?. Biochemistry and Cell Biology, 82(1), 87 - 98.

    2003

    • Loewen CJ, Roy A, Levine TP (2003). A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. The EMBO Journal, 22(9), 2025 - 2035. doi:10.1093/emboj/cdg201

    2002

    • Loewen CJ, Levine TP (2002). Cholesterol Homeostasis: Not until the SCAP Lady INSIGs. Current Biology, 12(22), R779 - R781. doi:10.1016/S0960-9822(02)01292-7
    • Levine TP, Munro S (2002). Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Current Biology, 12(9), 695 - 704.

    2001

    • Levine TP, Munro S (2001). Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction. Molecular Biology of the Cell, 12(6), 1633 - 1644.

    2000

    • (2000). Inositol phosphorylceramide synthase is located in the Golgi apparatus of Saccharomyces cerevisiae. Molecular Biology of the Cell, 11(7), 2267 - 2281.

    1993

    • Levine TP, Chain BM (1993). Endocytic activity of dendritic cells is similar to other antigen presenting cells.. Adv Exp Med Biol, 329, 11 - 15.

    1992

    • Levine TP, Chain BM (1992). Endocytosis by antigen presenting cells: dendritic cells are as endocytically active as other antigen presenting cells.. Proc Natl Acad Sci U S A, 89(17), 8342 - 8346.

    1991

    • Levine TP, Chain BM (1991). The cell biology of antigen processing.. Crit Rev Biochem Mol Biol, 26(5-6), 439 - 473. doi:10.3109/10409239109086790

    • Roy AAL, T (). Reconstitution of a membrane contact site with one protein: Osh1 at the nucleus vacuole junction. , , - .