Overview

The goal of my research is to identify the regulatory proteins that control vesicle transport in the yeast Saccharomyces cerevisiae, in order to understand how underlying defects in protein and lipid trafficking contribute to human disease. Vesicle transport is required to switch off signaling receptors that would otherwise promote unregulated cell growth. Retrograde transport also carries signals that promote the continued survival of neurons, and defects in the machinery responsible for retrograde transport are believed to be a cause of motor neuron disease. Because vesicle transport processes are highly conserved, they can be studied in a very simple organism, and the findings applied directly to the study of human cells. Yeast genetics is therefore a powerful tool for the discovery of fundamental cellular mechanisms relevant to human health.

Publications

Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites
The Journal of Cell Biology
Björn D.M. Bean, Samantha K. Dziurdzik, Kathleen L. Kolehmainen, Claire M.S. Fowler, Waldan K. Kwong, Leslie I. Grad, Michael Davey, Cayetana Schluter, Elizabeth Conibear
DOI: 10.1083/jcb.201804111
07/2018

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface
Traffic
Sai T. Dharwada, Lauren E. Dalton, Björn D. M. Bean, Nirmala Padmanabhan, Catherine Choi, Cayetana Schluter, Michael Davey, Elizabeth Conibear
DOI: 10.1111/tra.12553
04/2018

Targeting the Ras palmitoylation/depalmitoylation cycle in cancer
Biochemical Society Transactions
David Tse Shen Lin, Nicholas G. Davis, Elizabeth Conibear
DOI: 10.1042/bst20160303
06/2017

Quantitative high-content imaging identifies novel regulators of Neo1 trafficking at endosomes
Molecular Biology of the Cell
Lauren E. Dalton, Björn D. M. Bean, Michael Davey, Elizabeth Conibear
DOI: 10.1091/mbc.e16-11-0772
04/2017

Cargo selectivity of yeast sorting nexins
Traffic
Björn D.M. Bean, Michael Davey, Elizabeth Conibear
DOI: 10.1111/tra.12459
01/2017

Enzymatic protein depalmitoylation by acyl protein thioesterases
Biochemical Society Transactions
David T.S. Lin, Elizabeth Conibear
DOI: 10.1042/bst20140235
04/2015

Rab5-family guanine nucleotide exchange factors bind retromer and promote its recruitment to endosomes
Molecular Biology of the Cell
B. D. M. Bean, M. Davey, J. Snider, M. Jessulat, V. Deineko, M. Tinney, I. Stagljar, M. Babu, E. Conibear
DOI: 10.1091/mbc.e14-08-1281
01/2015

ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization
eLife
David Tse Shen Lin, Elizabeth Conibear
DOI: 10.7554/elife.11306
2015

The alternate AP-1 adaptor subunit Apm2 interacts with the Mil1 regulatory protein and confers differential cargo sorting
Molecular Biology of the Cell
S. T. Whitfield, H. E. Burston, B. D. M. Bean, N. Raghuram, L. Maldonado-Baez, M. Davey, B. Wendland, E. Conibear
DOI: 10.1091/mbc.e15-09-0621
2015

Single point mutation in Rabenosyn-5 in a female with intractable seizures and evidence of defective endocytotic trafficking
Orphanet Journal of Rare Diseases
Sylvia Stockler, Silvia Corvera, David Lambright, Kevin Fogarty, Ekaterina Nosova, Deborah Leonard, Robert Steinfeld, Cameron Ackerley, Casper Shyr, Nicolas Au, Kathrin Selby, Margot van Allen, Hilary Vallance, Ron Wevers, David Watkins, David Rosenblatt, Colin J Ross, Elizabeth Conibear, Wyeth Wasserman, Clara van Karnebeek
DOI: 10.1186/s13023-014-0141-5
09/2014

The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington's disease
Human Molecular Genetics
Stefanie L. Butland, Shaun S. Sanders, Mandi E. Schmidt, Sean-Patrick Riechers, David T.S. Lin, Dale D.O. Martin, Kuljeet Vaid, Rona K. Graham, Roshni R. Singaraja, Erich E. Wanker, Elizabeth Conibear, Michael R. Hayden
DOI: 10.1093/hmg/ddu137
04/2014

Large-Scale Analysis of Membrane Transport in Yeast Using Invertase Reporters
Membrane Trafficking
Lauren Dalton and Michael Davey and Elizabeth Conibear
DOI: 10.1007/978-1-4939-2309-0_27
2014

Vesicle and organelle formation: making connections
Molecular Biology of the Cell
E. Conibear, B. J. Nichols
DOI: 10.1091/mbc.e12-12-0875
03/2013

Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae
Nature
Mohan Babu, James Vlasblom, Shuye Pu, Xinghua Guo, Chris Graham, Björn D. M. Bean, Helen E. Burston, Franco J. Vizeacoumar, Jamie Snider, Sadhna Phanse, Vincent Fong, Yuen Yi C. Tam, Michael Davey, Olha Hnatshak, Navgeet Bajaj, Shamanta Chandran, Thanuja Punna, Constantine Christopolous, Victoria Wong, Analyn Yu, Gouqing Zhong, Joyce Li, Igor Stagljar, Elizabeth Conibear, Shoshana J. Wodak, Andrew Emili, Jack F. Greenblatt
DOI: 10.1038/nature11354
09/2012

VPS35 Mutations in Parkinson Disease
The American Journal of Human Genetics
Carles Vilariño-Güell, Christian Wider, Owen A. Ross, Justus C. Dachsel, Jennifer M. Kachergus, Sarah J. Lincoln, Alexandra I. Soto-Ortolaza, Stephanie A. Cobb, Greggory J. Wilhoite, Justin A. Bacon, Bahareh Behrouz, Heather L. Melrose, Emna Hentati, Andreas Puschmann, Daniel M. Evans, Elizabeth Conibear, Wyeth W. Wasserman, Jan O. Aasly, Pierre R. Burkhard, Ruth Djaldetti, Joseph Ghika, Faycal Hentati, Anna Krygowska-Wajs, Tim Lynch, Eldad Melamed, Alex Rajput, Ali H. Rajput, Alessandra Solida, Ruey-Meei Wu, Ryan J. Uitti, Zbigniew K. Wszolek, François Vingerhoets, Matthew J. Farrer
DOI: 10.1016/j.ajhg.2011.06.001
07/2011

Vesicle Transport: Springing the TRAPP
Current Biology
Elizabeth Conibear
DOI: 10.1016/j.cub.2011.05.045
07/2011

Organization and Assembly of the TRAPPII Complex
Traffic
Catherine Choi, Michael Davey, Cayetana Schluter, Preet Pandher, Yuan Fang, Leonard J. Foster, Elizabeth Conibear
DOI: 10.1111/j.1600-0854.2011.01181.x
04/2011

Palmitoylation and depalmitoylation dynamics at a glance
Journal of Cell Science
Elizabeth Conibear, Nicholas G. Davis
DOI: 10.1242/jcs.059287
11/2010

Converging views of endocytosis in yeast and mammals
Current Opinion in Cell Biology
Elizabeth Conibear
DOI: 10.1016/j.ceb.2010.05.009
08/2010

Regulators of yeast endocytosis identified by systematic quantitative analysis
The Journal of Cell Biology
Helen E. Burston, Lymarie Maldonado-Báez, Michael Davey, Benjamen Montpetit, Cayetana Schluter, Beverly Wendland, Elizabeth Conibear
DOI: 10.1083/jcb.200811116
06/2009

Identification of the Novel TRAPP Associated Protein Tca17
Traffic
Ben Montpetit, Elizabeth Conibear
DOI: 10.1111/j.1600-0854.2009.00895.x
06/2009

The Endocytic Pathway
Trafficking Inside Cells
Elizabeth Conibear, Yuen Yi C. Tam
DOI: 10.1007/978-0-387-93877-6_4
2009

Discovery and Expansion of Gene Modules by Seeking Isolated Groups in a Random Graph Process
PLoS ONE
Jochen Brumm, Elizabeth Conibear, Wyeth W. Wasserman, Jennifer Bryan
DOI: 10.1371/journal.pone.0003358
10/2008

An endocytic mechanism for haemoglobin-iron acquisition inCandida albicans
Molecular Microbiology
Ziva Weissman, Revital Shemer, Elizabeth Conibear, Daniel Kornitzer
DOI: 10.1111/j.1365-2958.2008.06277.x
07/2008

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex
Molecular Biology of the Cell
C. Schluter, K. K.Y. Lam, J. Brumm, B. W. Wu, M. Saunders, T. H. Stevens, J. Bryan, E. Conibear
DOI: 10.1091/mbc.e07-07-0659
04/2008

Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS
Amyotrophic Lateral Sclerosis
Miriam H. Meisler, Carsten Russ, Kate T. Montgomery, Matthew Greenway, Sean Ennis, Orla Hardiman, Denise A. Figlewicz, Nicole R. Quenneville, Elizabeth Conibear, Robert H. Brown
DOI: 10.1080/17482960801934403
01/2008

Genome-Wide Analysis of Membrane Transport Using Yeast Knockout Arrays
Membrane Trafficking
Helen E. Burston, Michael Davey, Elizabeth Conibear
DOI: 10.1007/978-1-59745-261-8_3
2008

Molecular Architecture and Functional Model of the Complete Yeast ESCRT-I Heterotetramer
Cell
Michael S. Kostelansky, Cayetana Schluter, Yuen Yi C. Tam, Sangho Lee, Rodolfo Ghirlando, Bridgette Beach, Elizabeth Conibear, James H. Hurley
DOI: 10.1016/j.cell.2007.03.016
05/2007

Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3
The Journal of Cell Biology
Karen K.Y. Lam, Michael Davey, Beimeng Sun, Amy F. Roth, Nicholas G. Davis, Elizabeth Conibear
DOI: 10.1083/jcb.200602049
07/2006

Toward the Systems Biology of Vesicle TransportThe Systems Biology of Vesicle Transport
Traffic
Nicole R. Quenneville, Elizabeth Conibear
DOI: 10.1111/j.1600-0854.2006.00436.x
05/2006

Domains within the GARP Subunit Vps54 Confer Separate Functions in Complex Assembly and Early Endosome Recognition
Molecular Biology of the Cell
N. R. Quenneville
DOI: 10.1091/mbc.e05-11-1002
01/2006

An E-MAP of the ER
Cell
Elizabeth Conibear
DOI: 10.1016/j.cell.2005.10.016
11/2005

Ykt6p Is a Multifunctional Yeast R-SNARE That Is Required for Multiple Membrane Transport Pathways to the Vacuole
Molecular Biology of the Cell
Y. Kweon
DOI: 10.1091/mbc.e02-10-0687
01/2003

An ESCRT into the Endosome
Molecular Cell
Elizabeth Conibear
DOI: 10.1016/s1097-2765(02)00601-9
08/2002

Studying yeast vacuoles
Guide to Yeast Genetics and Molecular and Cell Biology Part C
Elizabeth Conibear and Tom H. Stevens
DOI: 10.1016/s0076-6879(02)51861-9
2002

Vps51p Mediates the Association of the GARP (Vps52/53/54) Complex with the Late Golgi t-SNARE Tlg1p
Molecular Biology of the Cell
E. Conibear
DOI: 10.1091/mbc.e02-10-0654
2002

Vps52p, Vps53p, and Vps54p Form a Novel Multisubunit Complex Required for Protein Sorting at the Yeast Late Golgi
Molecular Biology of the Cell
E. Conibear, T. H. Stevens
DOI: 10.1091/mbc.11.1.305
01/2000

Identification of Rgp1p, a novel Golgi recycling factor, as a protein required for efficient localization of yeast casein kinase 1 to the plasma membrane
Journal of Cell Science
Panek, H.R. and Conibear, E. and Bryan, J.D. and Colvin, R.T. and Goshorn, C.D. and Robinson, L.C.
2000

Multiple sorting pathways between the late Golgi and the vacuole in yeast
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Elizabeth Conibear, Tom H Stevens
DOI: 10.1016/s0167-4889(98)00058-5
08/1998

Vacuolar biogenesis in yeast: Sorting out the sorting proteins
Cell
Elizabeth Conibear, Tom H. Stevens
DOI: 10.1016/0092-8674(95)90088-8
11/1995

Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane
The Journal of Cell Biology
S. F. Nothwehr
DOI: 10.1083/jcb.129.1.35
04/1995

A chimera of the cytoplasmic tail of the mannose 6-phosphate/IGF-II receptor and lysozyme localizes to the TGN rather than prelysosomes where the bulk of the endogenous receptor is found
Journal of Cell Science
Conibear, E. and Pearse, B.M.
1994

Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor
The EMBO Journal
PubMed: PMC400912
04/1989

Research

Current Project
Vesicle traffic is regulated by factors that select cargo for incorporation into a forming vesicle and direct its docking and fusion with the appropriate target membrane. The machinery that controls transport between two intracellular compartments - the endosome and the trans-Golgi network - is of particular interest because these compartments act as relay stations, directing a large number of different sorting events. We have used a genetic approach in the yeast model system to identify four components of a conserved protein complex (GARP: Golgi-associated retrograde protein complex) that directs the targeting of transport vesicles with the trans-Golgi network. We are currently using genetic, cell biological and biochemical techniques to analyze the interactions that link this vesicle targeting complex to other components of the membrane fusion machinery.

Recent advances in genome-wide phenotypic screening in yeast, combined with powerful bioinformatics analyses, hold great promise for the rapid and comprehensive identification of novel multi-subunit complexes. Functional genomics is expected to uncover most of the genes required for the trafficking of proteins and lipids through Golgi and endosomal compartments. In genome-wide screens, we have identified sets of genes likely to act together at common regulatory steps in protein sorting. We are now using biochemical/cell biological assays to characterize interacting proteins and analyze their role in protein and lipid trafficking in detail. Tackling a problem at many different levels - from genome-wide discovery studies in yeast, to the biochemical and cell biological characterization of specific protein complexes, to the investigation of homologous proteins in mammalian cells - allows an in-depth analysis of protein function and ensures that discoveries made in a simple model organism are efficiently translated to the study of medically relevant processes in mammalian cells.

Honours & Awards

Canada Foundation for Innovation Grant, 2013

UBC Killam Teaching Prize, 2014

Research Group Members

Michael Davey
Shawn Whitfield
Rory Long
Shawn Shortill, MSc Student in Medical Genetics
Syndey Holme
Vaishnavi Sridhar
Alexis Zi Le Shih
Bjorn Bean
Juan Burckhardt
Harmit Kainth
Helena Sokolovska
Samantha Katarzyna Dziurdzik