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

N-terminal signals in the SNX-BAR paralogs Vps5 and Vin1 guide coat complex formation
Shawn P. Shortill and Mia S. Frier and Michael Davey and Elizabeth Conibear
DOI: 10.1101/2024.01.24.576755
01/2024

N-terminal signals in the SNX-BAR paralogs Vps5 and Vin1 guide endosomal coat complex formation
Molecular biology of the cell
DOI: 10.1091/mbc.E24-01-0043
2024

An acylated N-terminus and a conserved loop regulate the activity of the ABHD17 de-acylase
bioRxiv
DOI: 10.1101/2024.05.14.594217
2024

Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae
Microbial Cell Factories
DOI: 10.1186/s12934-024-02298-0
2024

Genome-wide screen identifies new set of genes for improved heterologous laccase expression inSaccharomyces cerevisiae
Garrett Strawn and Ryan Wong and Barry Young and Michael Davey and Corey Nislow and Elizabeth Conibear and Christopher Loewen and Thibault Mayor
DOI: 10.1101/2023.07.10.548373
07/2023

The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
eLife
Shortill, S.P. and Frier, M.S. and Wongsangaroonsri, P. and Davey, M. and Conibear, E.
DOI: 10.7554/eLife.77035
2022

You can go your own way: SNX-BAR coat complexes direct traffic at late endosomes
Current Opinion in Cell Biology
Shortill, S.P. and Frier, M.S. and Conibear, E.
DOI: 10.1016/j.ceb.2022.102087
2022

The Vps13 Family of Lipid Transporters and Its Role at Membrane Contact Sites
International Journal of Molecular Sciences
Samantha Dziurdzik and Elizabeth Conibear
DOI: 10.3390/ijms22062905
03/2021

Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution
bioRxiv
Castro, I.G. and Shortill, S.P. and Dziurdzik, S.K. and Cadou, A. and Ganesan, S. and Fenech, E.J. and Meyer, H. and Fadel, A. and David, Y. and Davey, M. and Mattes, C. and Valenti, R. and Ernst, R. and Zaremberg, V. and Levine, T.P. and Stefan, C.J. and Conibear, E. and Schuldiner, M.
DOI: 10.1101/2021.10.17.464712
2021

Palmitoylation targets the Calcineurin phosphatase to the Phosphatidylinositol 4-kinase complex at the plasma membrane
bioRxiv
Ulengin-Talkish, I. and Parson, M.A.H. and Jenkins, M.L. and Roy, J. and Shih, A.Z.L. and St-Denis, N. and Gulyas, G. and Balla, T. and Gingras, A.-C. and Várnai, P. and Conibear, E. and Burke, J.E. and Cyert, M.S.
DOI: 10.1101/2021.07.14.451536
2021

The VINE complex is a VPS9-domain GEF-containing SNX-BAR coat involved in endosomal sorting
bioRxiv
Shortill, S.P. and Frier, M.S. and Davey, M. and Conibear, E.
DOI: 10.1101/2021.11.29.470412
2021

Uncovering The Unique Functions And Regulation Of The Palmitoylated Calcineurin Isoform, CNß1
The FASEB Journal
Idil Ulengin-Talkish and Rachel Bond and Nicole St-Denis and Anne-Claude Gingras and Alexis Shih and Elizabeth Conibear and Tamas Balla and Peter Varnai and Martha S. Cyert
DOI: 10.1096/fasebj.2020.34.s1.07593
04/2020

A VPS13D spastic ataxia mutation disrupts the conserved adaptor-binding site in yeast Vps13
Human Molecular Genetics
Dziurdzik, S.K. and Bean, B.D.M. and Davey, M. and Conibear, E.
DOI: 10.1093/hmg/ddz318
2020

A VPS13D spastic ataxia mutation disrupts the conserved adaptor binding site in yeast Vps13
bioRxiv
Dziurdzik, S.K. and Bean, B.D.M. and Davey, M. and Conibear, E.
DOI: 10.1101/768366
2019

Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites
Journal of Cell Biology
Bean, B.D.M. and Dziurdzik, S.K. and Kolehmainen, K.L. and Fowler, C.M.S. and Kwong, W.K. and Grad, L.I. and Davey, M. and Schluter, C. and Conibear, E.
DOI: 10.1083/JCB.201804111
2018

The chaperone Chs7 forms a stable complex with Chs3 and promotes its activity at the cell surface
Traffic
Dharwada, S.T. and Dalton, L.E. and Bean, B.D.M. and Padmanabhan, N. and Choi, C. and Schluter, C. and Davey, M. and Conibear, E.
DOI: 10.1111/tra.12553
2018

An Interorganellar Bidding War: Vps13 Localization by Competitive Organelle-Specific Adaptors
Contact
DOI: 10.1177/2515256418814621
2018

Quantitative high-content imaging identifes novel regulators of Neo1 traffcking at endosomes
Molecular Biology of the Cell
Dalton, L.E. and Bean, B.D.M. and Davey, M. and Conibear, E.
DOI: 10.1091/mbc.E16-11-0772
2017

Cargo selectivity of yeast sorting nexins
Traffic
Bean, B.D.M. and Davey, M. and Conibear, E.
DOI: 10.1111/tra.12459
2017

Targeting the Ras palmitoylation/depalmitoylation cycle in cancer
Biochemical Society Transactions
Lin, D.T.S. and Davis, N.G. and Conibear, E.
DOI: 10.1042/BST20160303
2017

The alternate AP-1 adaptor subunit Apm2 interacts with the Mil1 regulatory protein and confers differential cargo sorting
Molecular Biology of the Cell
Whitfield, S.T. and Burston, H.E. and Bean, B.D.M. and Raghuram, N. and Maldonado-Báez, L. and Davey, M. and Wendland, B. and Conibear, E.
DOI: 10.1091/mbc.E15-09-0621
2016

Large-scale analysis of membrane transport in yeast using invertase reporters
Methods in Molecular Biology
Dalton, L. and Davey, M. and Conibear, E.
DOI: 10.1007/978-1-4939-2309-0_27
2015

Rab5-family guanine nucleotide exchange factors bind retromer and promote its recruitment to endosomes
Molecular Biology of the Cell
Bean, B.D.M. and Davey, M. and Snider, J. and Jessulat, M. and Deineko, V. and Tinney, M. and Stagljar, I. and Babu, M. and Conibear, E.
DOI: 10.1091/mbc.E14-08-1281
2015

Enzymatic protein depalmitoylation by acyl protein thioesterases
Biochemical Society Transactions
Lin, D.T.S. and Conibear, E.
DOI: 10.1042/BST20140235
2015

ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization
eLife
Lin, D.T.S. and Conibear, E.
DOI: 10.7554/eLife.11306
2015

Single point mutation in Rabenosyn-5 in a female with intractable seizures and evidence of defective endocytotic trafficking
Orphanet Journal of Rare Diseases
Stockler, S. and Corvera, S. and Lambright, D. and Fogarty, K. and Nosova, E. and Leonard, D. and Steinfeld, R. and Ackerley, C. and Shyr, C. and Au, N. and Selby, K. and Van Allen, M. and Vallance, H. and Wevers, R. and Watkins, D. and Rosenblatt, D. and Ross, C.J. and Conibear, E. and Wasserman, W. and Van Karnebeek, C.
DOI: 10.1186/s13023-014-0141-5
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
Butland, S.L. and Sanders, S.S. and Schmidt, M.E. and Riechers, S.-P. and Lin, D.T.S. and Martin, D.D.O. and Vaid, K. and Graham, R.K. and Singaraja, R.R. and Wanker, E.E. and Conibear, E. and Hayden, M.R.
DOI: 10.1093/hmg/ddu137
2014

Vesicle and organelle formation: making connections.
Molecular biology of the cell
DOI: 10.1091/mbc.e12-12-0875
2013

Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae
Nature
Babu, M. and Vlasblom, J. and Pu, S. and Guo, X. and Graham, C. and Bean, B.D.M. and Burston, H.E. and Vizeacoumar, F.J. and Snider, J. and Phanse, S. and Fong, V. and Tam, Y.Y.C. and Davey, M. and Hnatshak, O. and Bajaj, N. and Chandran, S. and Punna, T. and Christopolous, C. and Wong, V. and Yu, A. and Zhong, G. and Li, J. and Stagljar, I. and Conibear, E. and Wodak, S.J. and Emili, A. and Greenblatt, J.F.
DOI: 10.1038/nature11354
2012

Erratum: VPS35 mutations in Parkinson disease (American Journal of Human Genetics (2011) 89 (162-167))
American Journal of Human Genetics
Vilariño-Güell, C. and Wider, C. and Ross, O.A. and Dachsel, J.C. and Kachergus, J.M. and Lincoln, S.J. and Soto-Ortolaza, A.I. and Cobb, S.A. and Wilhoite, G.J. and Bacon, J.A. and Behrouz, B. and Melrose, H.L. and Hentati, E. and Puschmann, A. and Evans, D.M. and Conibear, E. and Wasserman, W.W. and Aasly, J.O. and Burkhard, P.R. and Djaldetti, R. and Ghika, J. and Hentati, F. and Krygowska-Wajs, A. and Lynch, T. and Melamed, E. and Rajput, A. and Rajput, A.H. and Solida, A. and Wu, R.-M. and Uitti, R.J. and Wszolek, Z.K. and Vingerhoets, F. and Farrer, M.J.
DOI: 10.1016/j.ajhg.2011.07.018
2011

Vesicle transport: Springing the TRAPP
Current Biology
Conibear, E.
DOI: 10.1016/j.cub.2011.05.045
2011

Organization and Assembly of the TRAPPII Complex
Traffic
Choi, C. and Davey, M. and Schluter, C. and Pandher, P. and Fang, Y. and Foster, L.J. and Conibear, E.
DOI: 10.1111/j.1600-0854.2011.01181.x
2011

VPS35 mutations in parkinson disease
American Journal of Human Genetics
Vilariño-Güell, C. and Wider, C. and Ross, O.A. and Dachsel, J.C. and Kachergus, J.M. and Lincoln, S.J. and Soto-Ortolaza, A.I. and Cobb, S.A. and Wilhoite, G.J. and Bacon, J.A. and Bahareh Behrouz and Melrose, H.L. and Hentati, E. and Puschmann, A. and Evans, D.M. and Conibear, E. and Wasserman, W.W. and Aasly, J.O. and Burkhard, P.R. and Djaldetti, R. and Ghika, J. and Hentati, F. and Krygowska-Wajs, A. and Lynch, T. and Melamed, E. and Rajput, A. and Rajput, A.H. and Solida, A. and Wu, R.-M. and Uitti, R.J. and Wszolek, Z.K. and Vingerhoets, F. and Farrer, M.J.
DOI: 10.1016/j.ajhg.2011.06.001
2011

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

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

Identification of the novel TRAPP associated protein Tca17
Traffic
Montpetit, B. and Conibear, E.
DOI: 10.1111/j.1600-0854.2009.00895.x
2009

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

Regulators of yeast endocytosis identified by systematic quantitative analysis
Journal of Cell Biology
Burston, H.E. and Maldonado-Báez, L. and Davey, M. and Montpetit, B. and Schluter, C. and Wendland, B. and Conibear, E.
DOI: 10.1083/jcb.200811116
2009

Global analysis of yeast endosomal transport identifies the Vps55/68 sorting complex
Molecular Biology of the Cell
Schluter, C. and Lam, K.K.Y. and Brumm, J. and Wu, B.W. and Saunders, M. and Stevens, T.H. and Bryan, J. and Conibear, E.
DOI: 10.1091/mbc.E07-07-0659
2008

An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans
Molecular Microbiology
Weissman, Z. and Shemer, R. and Conibear, E. and Kornitzer, D.
DOI: 10.1111/j.1365-2958.2008.06277.x
2008

Genome-wide analysis of membrane transport using yeast knockout arrays
Methods in Molecular Biology
Burston, H.E. and Davey, M. and Conibear, E.
DOI: 10.1007/978-1-59745-261-8_3
2008

Discovery and expansion of gene modules by seeking isolated groups in a random graph process
PLoS ONE
Brumm, J. and Conibear, E. and Wasserman, W.W. and Bryan, J.
DOI: 10.1371/journal.pone.0003358
2008

Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS
Amyotrophic Lateral Sclerosis
Meisler, M.H. and Russ, C. and Montgomery, K.T. and Greenway, M. and Ennis, S. and Hardiman, O. and Figlewicz, D.A. and Quenneville, N.R. and Conibear, E. and Brown Jr., R.H.
DOI: 10.1080/17482960801934403
2008

Molecular Architecture and Functional Model of the Complete Yeast ESCRT-I Heterotetramer
Cell
Kostelansky, M.S. and Schluter, C. and Tam, Y.Y.C. and Lee, S. and Ghirlando, R. and Beach, B. and Conibear, E. and Hurley, J.H.
DOI: 10.1016/j.cell.2007.03.016
2007

Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3
Journal of Cell Biology
Lam, K.K.Y. and Davey, M. and Sun, B. and Roth, A.F. and Davis, N.G. and Conibear, E.
DOI: 10.1083/jcb.200602049
2006

Domains within the GARP subunit Vps54 confer separate functions in complex assembly and early endosome recognition
Molecular Biology of the Cell
Quenneville, N.R. and Chao, T.-Y. and McCaffery, J.M. and Conibear, E.
DOI: 10.1091/mbc.E05-11-1002
2006

Toward the systems biology of vesicle transport
Traffic
Quenneville, N.R. and Conibear, E.
DOI: 10.1111/j.1600-0854.2006.00436.x
2006

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

Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlg1p
Molecular Biology of the Cell
Conibear, E. and Cleck, J.N. and Stevens, T.H.
DOI: 10.1091/mbc.E02-10-0654
2003

Ykt6p is a multifunctional yeast R-SNARE that is required for multiple membrane transport pathways to the vacuole
Molecular Biology of the Cell
Kweon, Y. and Rothe, A. and Conibear, E. and Stevens, T.H.
DOI: 10.1091/mbc.E02-10-0687
2003

An ESCRT into the endosome
Molecular Cell
Conibear, E.
DOI: 10.1016/S1097-2765(02)00601-9
2002

Studying yeast vacuoles
Methods in Enzymology
Conibear, E. and Stevens, T.H.
DOI: 10.1016/S0076-6879(02)51861-9
2002

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 HR and Conibear E and Bryan JD and Colvin RT and Goshorn CD and Robinson LC
PubMed: 11082047
12/2000

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

Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi
Molecular Biology of the Cell
Conibear, E. and Stevens, T.H.
DOI: 10.1091/mbc.11.1.305
2000

Multiple sorting pathways between the late Golgi and the vacuole in yeast
Biochimica et Biophysica Acta - Molecular Cell Research
Conibear, E. and Stevens, T.H.
DOI: 10.1016/S0167-4889(98)00058-5
1998

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

Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane
Journal of Cell Biology
Nothwehr, S.F. and Conibear, E. and Stevens, T.H.
DOI: 10.1083/jcb.129.1.35
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 BM
PubMed: 8056846
04/1994

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.F.
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

Specificity of binding of clathrin adaptors to signals on the mannose 6-phosphate/insulin-like growth factor II receptor
EMBO Journal
Glickman, J.N. and Conibear, E. and Pearse, B.M.F.
DOI: 10.1002/j.1460-2075.1989.tb03471.x
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.

Grants

Canada Foundation for Innovation Grant, 2013

Honours & Awards

UBC Killam Teaching Prize, 2014

Research Group Members

Paige Blair, Graduate Student
Veronika Bumbulovic, Research Assistant
Kenzie Chute, Research Assistant
Michael Davey, Research Asst/Tech 4
Hailey Eng
Mia Frier, PhD Candidate
Marian Gauzshtein, Research Assistant
Jordan Grant, Research Assistant
Jacob Gravelle, Research Assistant
Sydney Holme, PhD Student
Kevin Jeffers, PhD Candidate
Gabriel Law, Research Assistant
Vivian MacLennan, Research Assistant
Sera Park, Lab Assistant
Aubrey Peters, Research Assistant
Victoria Rogers, Research Assistant
Gurpreet Sidhu, Research Assistant
Wendy Tso, Research Assistant