
Overview
Background
Protein trafficking in disease
The highly co-ordinated movement of the thousands of distinct membrane proteins between the cell surface and intracellular compartments is a critical factor in health and disease. This movement controls the organisation of cells in tissues and communication between cells and their environment. The success of this process depends on the regulated sorting and trafficking of proteins within the highly dynamic endosomal compartments of the cell in processes that are emerging as important drivers of neurodegenerative disease, cancer and metabolic pathologies. An understanding of how endosomal traffic is regulated, and how lysosomal traffic and degradation are modulated, is critical for providing insights into disease and devising new therapeutic approaches.
Major Undergraduate Teaching Activity
SBMS Honours Convenor (BBiomed, BAdvcSci (Cell Biology and Biomedical Science majors) & BSci (Cell Biology and Biomedical Science majors)
SBMS Honours Coordinator (BIOM6191 & BIOM6192)
BIOL2200 – Molecular Cell Biology I Lecturer and practical cooridinator
BIOL3006 – Molecular Cell Biology II Lecturer
Student Supervisor for Research Projects in Biomedical Sciences (SCIE3220/1 or Honours)
Availability
- Associate Professor Rohan Teasdale is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Doctor of Philosophy, Monash University
Research interests
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Retromer – A master regulator of endosome protein trafficking
Fidelity of transport through the endosomal system requires mechanisms that precisely sort cargoes for delivery to a range of different destinations. This is achieved by cargo engaging specific sorting machinery that is responsible for their accumulation into tubules that then undergo scission to generate endosome-transport carriers (ETCs). Once formed, these carrier vesicles engage the machinery at the target membrane, resulting in cargo delivery to the specific membrane, e.g. plasma membrane. Retromer has been identified to have a central role in this process and it is the spatial and temporal coordination of the interaction between Retromer and associated proteins that determines the properties of the individual endosome-transport carriers formed. We are currently investigating the contribution each of the variant Retromer complexes has on the formation of the distinct endosome-transport carrier types and to the sorting of a range of cargo actively transported by these vesicles.
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Retromer’s role in neurodegeneration
Our research into defining the composition of a mammalian endosomal protein complex, termed Retromer, has made major contributions to its recent emergence as a central, critical regulator of early endosome protein trafficking. Recently, pathogenetic mutations within a Retromer subunit, Vps35, have been directly associated with causing late onset Parkinson’s disease. More broadly, endosomes are emerging to have a central role in the pathobiology of neurodegenerative diseases, including Alzheimer’s & Parkinson’s diseases. In ongoing studies, we have found that disruption of known Retromer components contributes to the cellular pathology phenotypes associated with Parkinson’s disease (PD). It is proposed that perturbing the Retromer-mediated formation of endosome to trans-Golgi Network (TGN) transport carriers directly underpins the manifestation of cellular phenotypes, such as alpha-synuclein aggregation, that lead to the development of PD. Significantly, preliminary studies have revealed that the pharmacological enhancement of Retromer function is able to reduce the severity of PD-associated cellular phenotypes, establishing Retromer as a potential therapeutic target. As Retromer has also been implicated in Alzheimer’s disease, the Group’s research is relevant to multiple, progressive, neurological disorders that are the most common causes of dementia.
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Define the roles of the SNX-RGS proteins in membrane tethering and lipid homeostasis in adipocytes
Our cells work constantly to maintain a balance between the accumulation and degradation of proteins, lipids and other metabolites. This homeostasis is regulated in many ways, but prominent mechanisms include the synthesis, sorting and breakdown of these biomolecules within membrane-bound organelles including the endoplasmic reticulum (ER), endosomes, lysosomes and autophagosomes, and the storage of lipids in compartments called lipid droplets (LDs). Sorting nexins (SNXs) are a large family of proteins that are all associated with endomembrane compartments. The four human proteins, SNX14, SNX13, SNX19 and SNX25, comprise a unique sub-family referred to as the SNX- RGS molecules. However, the precise function of these proteins is still not clear, and how they work at the molecular level is largely unknown. Our studies are now pointing to a central role in mediating interactions between endosomal membranes, the endoplasmic reticulum (ER) and fatty-acid storage compartments called lipid droplets (LDs). Our working model is that SNX-RGS proteins are membrane tethers that control trafficking, signalling and exchange of lipids between the ER, LDs and endosomal compartments, where they are important for normal lipid metabolism and proper functioning of the endomembrane system; this in turn can affect the downstream degradation of other cellular waste by lysosomal and autophagic pathways
Research impacts
My long-term research focus has been on the discovery and characterization of novel protein trafficking components. I am recognized for my contribution to the discovery of endosome associated proteins and defining their molecular function within various endosomal associated protein trafficking pathways. I am recognized internationally for cell biology research on endosomal protein complexes and protein trafficking pathways, which are currently emerging as key contributors to normal physiological processes and neurodegenerative diseases. My research vision in endosome associated biology represents an ambitious and comprehensive plan that spans the detailed characterisation of individual proteins to genome-wide screening.
Throughout my career I have 118 research publications that have attracted a total of >12,000 citations. My h- index=52 (Web of Science May 2024).
Major published discoveries and impacts originating from my Protein Trafficking in Disease laboratory at the University of Queensland include:
• We discovered a novel Retromer complex defined by incorporation of Vps26 in the Vps26B subunit. We showed that the two distinct Retromer complexes defined by different Vps26 paralogues are not functionally equivalent and that they have unique cargo binding specificity (Traffic, 2005, 2008, 2011; Cell Biol. Int, 2014).
We recently clarified a controversy about the molecular action of retromer by demonstrating that the essential role of retromer in the selective incorporation of cargo into a specific type of endosome transport carrier. This included the generation of a series of novel cell models using CrispR-mediated KO of the Retromer and its associated proteins (J. Cell Biol, 2019). Incorporation of cation-independent mannose 6-phosphate receptor (CI- M6PR) into endosome transport carriers via a retromer-dependent process is restricted to those tethered by GCC88 but not golgin-97 or golgin-245. This retromer-dependent retrograde cargo trafficking pathway requires SNX3, but not other retromer-associated cargo binding proteins, such as SNX27 or SNX-BAR proteins.
• We defined, for the first time, a role for Retromer in GLUT-4 Storage Vesicle (GSV) formation and adipogenesis in primary cell line models. In mature adipocytes, we demonstrated that Retromer is recruited to GSVs and is essential for both, the maintenance of GSV protein levels and the formation of GSV (FASEB Journal, 2016).
• Retromer has been implicated in both Alzheimer’s and Parkinson’s neurological diseases and we have recently published the first manuscripts showing the molecular mechanisms underlying this genetic cause of Parkinson’s disease (Traffic, 2014, J. Biol Chem, 2016).
• I have continued to investigate the sorting nexin/PX domain family of protein trafficking molecules that I originally discovered and defined (Biochem J. 2001; 2012). This has included characterising SNX27 and the molecular details of how it interacts with membrane cargo and the retromer complex (J. Biol Chem, 2018; Mol. Biol. Cell, 2016; Nature Struct. Mol. Biol., 2016, PNAS, 2013, 2014)
Works
Search Professor Rohan Teasdale’s works on UQ eSpace
2017
Journal Article
Retromer’s role in endosomal trafficking and impaired function in neurodegenerative diseases
Follett, Jordan, Bugarcic, Andrea, Collins, Brett M. and Teasdale, Rohan D. (2017). Retromer’s role in endosomal trafficking and impaired function in neurodegenerative diseases. Current Protein and Peptide Science, 18 (7), 687-701. doi: 10.2174/1389203717666160311121246
2017
Conference Publication
Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
Paul, B., Kim, H. S., Kerr, M. C., Huston, W. M., Teasdale, R. D. and Collins, B. M. (2017). Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis. Annual Joint Meeting of the American Society for Cell Biology and the European Molecular Biology Organization (ASCB/EMBO), Philadelphia, PA United States, 2-6 December 2017. Bethesda, MD United States: American Society for Cell Biology.
2016
Journal Article
A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex
Clairfeuille, Thomas, Mas, Caroline, Chan, Audrey S. M., Yang, Zhe, Tello-Lafoz, Maria, Chandra, Mintu, Wigagdo, Jocelyn, Kerr, Markus, Blessy, Paul, Merida, Isabel, Teasdale, Rohan D., Pavlos, Nathan J., Anggono, Victor and Collins, Brett (2016). A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex. Nature Structural and Molecular Biology, 23 (10), 921-932. doi: 10.1038/nsmb.3290
2016
Journal Article
MTMR4 is required for the stability of the salmonella-containing vacuole
Teo, Wei X., Kerr, Markus C. and Teasdale, Rohan D. (2016). MTMR4 is required for the stability of the salmonella-containing vacuole. Frontiers in Cellular and Infection Microbiology, 6 (91) 91, 1-11. doi: 10.3389/fcimb.2016.00091
2016
Journal Article
Parkinson disease-linked Vps35 R524W mutation impairs the endosomal association of retromer and induces α-synuclein aggregation
Follett, Jordan, Bugarcic, Andrea, Yang, Zhe, Ariotti, Nicholas, Norwood, Suzanne J., Collins, Brett M., Parton, Robert G. and Teasdale, Rohan D. (2016). Parkinson disease-linked Vps35 R524W mutation impairs the endosomal association of retromer and induces α-synuclein aggregation. Journal of Biological Chemistry, 291 (35), 18283-18298. doi: 10.1074/jbc.M115.703157
2016
Journal Article
Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth
Chan, Audrey S. M., Clairfeuille, Thomas, Landao-Bassonga, Euphemie, Kinna, Genevieve, Ng, Pei Ying, Loo, Li Shen, Cheng, Tak Sum, Zheng, Minghao, Hong, Wanjin, Teasdale, Rohan D., Collins, Brett M. and Pavlos, Nathan J (2016). Sorting nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth. Molecular Biology of the Cell, 27 (8), 1367-1382. doi: 10.1091/mbc.E15-12-0851
2016
Journal Article
Sortilin is associated with the chlamydial inclusion and is modulated during infection
Teo, Wei Xuan, Kerr, Markus Charles, Huston, Wilhelmina May and Teasdale, Rohan David (2016). Sortilin is associated with the chlamydial inclusion and is modulated during infection. Biology Open, 5 (4), 429-435. doi: 10.1242/bio.016485
2016
Journal Article
Functional characterization of retromer in GLUT4 storage vesicle formation and adipocyte differentiation
Yang, Zhe, Hong, Lee Kian, Follett, Jordan, Wabitsch, Martin, Hamilton, Nicholas A., Collins, Brett, Bugarcic, Andrea and Teasdale, Rohan D. (2016). Functional characterization of retromer in GLUT4 storage vesicle formation and adipocyte differentiation. The FASEB Journal, 39 (3), 1037-1050. doi: 10.1096/fj.15-274704
2015
Journal Article
Modular detection of GFP-labeled proteins for rapid screening by electron microscopy in cells and organisms
Ariotti, Nicholas, Hall, Thomas, Rae, James, Ferguson, Charles, McMahon, Kerrie-Ann, Martel, Nick, Webb, Robyn E., Webb, Richard I., Teasdale, Rohan D. and Parton, Robert G. (2015). Modular detection of GFP-labeled proteins for rapid screening by electron microscopy in cells and organisms. Developmental Cell, 35 (4), 513-525. doi: 10.1016/j.devcel.2015.10.016
2015
Journal Article
Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2
Bugarcic, Andrea, Vetter, Irina, Chalmers, Silke, Kinna, Genevieve, Collins, Brett M. and Teasdale, Rohan D. (2015). Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2. Cell Biology International, 39 (11), 1299-1306. doi: 10.1002/cbin.10508
2015
Journal Article
SseK3 is a salmonella effector that binds trim32 and modulates the host's nf-kappa b signalling activity
Yang, Zhe, Soderholm, Amelia, Lung, Tania Wong Fok, Giogha, Cristina, Hill, Michelle M., Brown, Nathaniel F., Hartland, Elizabeth and Teasdale, Rohan D. (2015). SseK3 is a salmonella effector that binds trim32 and modulates the host's nf-kappa b signalling activity. PL o S One, 10 (9) e0138529, 1-20. doi: 10.1371/journal.pone.0138529
2015
Journal Article
Structure and membrane binding properties of the endosomal tetratricopeptide repeat (TPR) domain-containing sorting nexins SNX20 and SNX21
Clairfeuille, Thomas, Norwood, Suzanne J., Qi, Xiaying, Teasdale, Rohan D. and Collins, Brett M. (2015). Structure and membrane binding properties of the endosomal tetratricopeptide repeat (TPR) domain-containing sorting nexins SNX20 and SNX21. Journal of Biological Chemistry, 290 (23), 14504-14517. doi: 10.1074/jbc.M115.650598
2015
Journal Article
Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells
Ghai, Rajesh, Tello-Lafoz, Maria, Norwood, Suzanne J., Yang, Zhe, Clairefeuille, Thomas, Teasdale, Rohan D., Mérida, Isabel and Collins, Brett M. (2015). Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells. Journal of Cell Science, 128 (3), 553-565. doi: 10.1242/jcs.158204
2015
Journal Article
Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector
King, Nathan P., Newton, Patrice, Schuelein, Ralf, Brown, Darren L., Petru, Marketa, Zarsky, Vojtech, Dolezal, Pavel, Luo, Lin, Bugarcic, Andrea, Stanley, Amanda C., Murray, Rachael Z., Collins, Brett M., Teasdale, Rohan D., Hartland, Elizabeth L. and Stow, Jennifer L. (2015). Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector. Cellular Microbiology, 17 (6), 767-784. doi: 10.1111/cmi.12405
2015
Conference Publication
Parkinson-associated VPS35 mutations alter retromer cellular functions
Teasdale, R., Follett, J., Bugarcic, A., Yang, Z. and Collins, B. (2015). Parkinson-associated VPS35 mutations alter retromer cellular functions. 25th Biennial Meeting of the International Society for Neurochemistry Jointly with the 13th Meeting of the Asian Pacific Society for Neurochemistry in Conjunction with the 35th Meeting of the Australasian Neuroscience Society, Cairns, QLD Australia Conference, 23-27 August 2015. Chichester, West Sussex, United Kingdom: Wiley-Blackwell Publishing. doi: 10.1111/jnc.13185
2014
Journal Article
Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling
Mas, Caroline, Norwood, Suzanne J., Bugarcic, Andrea, Kinna, Genevieve, Leneva, Natalya, Kovtun, Oleksiy, Ghai, Rajesh, Yanez, Lorena E. Ona, Davis, Jasmine L., Teasdale, Rohan D. and Collins, Brett M. (2014). Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling. Journal of Biological Chemistry, 289 (41), 28554-28568. doi: 10.1074/jbc.M114.595959
2014
Journal Article
Little evidence that FAM65B belongs to the family of phox homology (PX) and bin/amphiphysin/rvs (BAR) domain-containing proteins
Teasdale, Rohan D. and Collins, Brett (2014). Little evidence that FAM65B belongs to the family of phox homology (PX) and bin/amphiphysin/rvs (BAR) domain-containing proteins. PNAS: Proceedings of the National Academy of Sciences of the United States of America, 111 (39), E4064-E4064. doi: 10.1073/pnas.1412755111
2014
Journal Article
A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer
Gallon, Matthew, Clairfeuille, Thomas, Steinberg, Florian, Mas, Caroline, Ghai, Rajesh, Sessions, Richard B., Teasdale, Rohan D., Collins, Brett M. and Cullen, Peter J. (2014). A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. Proceedings of the National Academy of Sciences of the United States of America, 111 (35), E3604-E3613. doi: 10.1073/pnas.1410552111
2014
Journal Article
Introduction to special issue on endosome dynamics
Teasdale, Rohan D. and Collins, Brett M. (2014). Introduction to special issue on endosome dynamics. Seminars in Cell and Developmental Biology, 31, 1-1. doi: 10.1016/j.semcdb.2014.05.001
2014
Journal Article
Live imaging of endosome dynamics
Kerr, Markus and Teasdale, Rohan D. (2014). Live imaging of endosome dynamics. Seminars in Cell and Developmental Biology, 31, 11-19. doi: 10.1016/j.semcdb.2014.03.027
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Rohan Teasdale is:
- Available for supervision
Before you email them, read our advice on how to contact a supervisor.
Available projects
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Enhancement of Retromer Function in Parkinson Disease
Retromer is responsible for coordinating protein trafficking from the endosomal compartment and its function has been directly associated with causing Parkinson’s Disease. Using cell models we have preliminary data that the enhancement of retromer function reduces the pathological changes within cells. This PhD project will examine ways to enhance the function of retromer and determine if it can prevent the progression of Parkinson Disease. This project will involve the development of cell and animal models to evaluate this hypothesis.
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Define the roles of the SNX-RGS proteins in membrane tethering and lipid homeostasis in adipocytes
Sorting nexins (SNXs) are a large family of proteins that are all associated with endomembrane compartments. The four human proteins, SNX14, SNX13, SNX19 and SNX25, comprise a unique sub-family referred to as the SNX- RGS molecules. However, the precise function of these proteins is still not clear, and how they work at the molecular level is largely unknown. Within the HDR project the expression and localisation of these proteins in adipocytes will be examined to determine if these SNX-RGS molecules associated with lipid droplets that formation when adipocytes differeientiate. The requirement of these molecules will be tested in knock-out cell models in combination with structure-function mutants.
Supervision history
Current supervision
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Master Philosophy
Exploring the Role of Retromer-Associated Proteins and SNX-RGS Subfamily Proteins in Protein Trafficking
Principal Advisor
Other advisors: Dr Zhe Yang
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Doctor Philosophy
Deciphering the endosomal machinery for GLUT4 trafficking and its role in diabetes
Principal Advisor
Other advisors: Dr Zhe Yang
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Doctor Philosophy
Deciphering the endosomal machinery for GLUT4 trafficking and its role in diabetes
Principal Advisor
Other advisors: Dr Zhe Yang
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Doctor Philosophy
Dissecting the role of retrograde trafficking machineries within the mammalian endosomal system
Principal Advisor
Other advisors: Dr Zhe Yang
Completed supervision
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2024
Master Philosophy
Exploring the Role of Retromer-Associated Proteins and SNX-RGS Subfamily Proteins in Protein Trafficking
Principal Advisor
Other advisors: Dr Zhe Yang
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2019
Doctor Philosophy
Defining the molecular action of retromer in retrograde trafficking pathways
Principal Advisor
Other advisors: Dr Zhe Yang
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2016
Doctor Philosophy
Examining the contribution of Host Cell Membrane Trafficking Pathways to Intracellular Infection Biology
Principal Advisor
Other advisors: Dr Markus Kerr
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2015
Doctor Philosophy
The Role of Sorting Nexins in Macropinocytosis and Salmonella Invasion
Principal Advisor
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2010
Doctor Philosophy
Investigating macropinocytosis: The role of sorting nexins in macropinosome biogenesis
Principal Advisor
Other advisors: Dr Markus Kerr
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2010
Doctor Philosophy
Computational methods to define the endosomal proteome
Principal Advisor
Other advisors: Professor Jennifer Stow
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2006
Doctor Philosophy
REDEFINING THE RETROMER
Principal Advisor
Other advisors: Professor Fiona Simpson
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2004
Doctor Philosophy
POST-GOLGI TRAFFICKING IN THE MAMMALIAN SECRETORY PATHWAY
Principal Advisor
Other advisors: Professor Jennifer Stow
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Doctor Philosophy
DEFINING THE MEMBRANE ORGANISATION OF EUKARYOTIC PROTEINS
Principal Advisor
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2023
Doctor Philosophy
SCF-Ubiquitin ligase dependent regulation of BNIP3 and NIX mitophagy receptors
Associate Advisor
Other advisors: Dr Julia Pagan
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2019
Doctor Philosophy
Structural studies of sorting nexin proteins from two distinct subfamilies
Associate Advisor
Other advisors: Professor Brett Collins
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2015
Doctor Philosophy
Structural basis of protein cargo transport by sorting nexins
Associate Advisor
Other advisors: Professor Brett Collins
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2012
Doctor Philosophy
Transcriptional complexity and post-transcriptional regulation of long noncoding RNAs
Associate Advisor
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2011
Doctor Philosophy
Structural Basis for Assembly and Membrane Modulating Properties of the Retromer Protein Coat Complex
Associate Advisor
Other advisors: Professor Brett Collins
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2008
Doctor Philosophy
The regulators of E-cadherin trafficking in polarized epithelial cells
Associate Advisor
Other advisors: Professor Jennifer Stow
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2008
Doctor Philosophy
Machine architectures for biological sequence classification
Associate Advisor
Other advisors: Professor Janet Wiles, Professor Mikael Boden
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2007
Doctor Philosophy
THE EXOCYTIC AND ENDOCYTIC TRAFFICKING OF E-CADHERIN IN EPITHELIAL CELLS
Associate Advisor
Other advisors: Professor Jennifer Stow
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2006
Doctor Philosophy
THE IDENTIFICATION AND CHARACTERISATION OF NOVEL GENES IN DEVELOPMENT
Associate Advisor
Other advisors: Professor Fiona Simpson
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2006
Doctor Philosophy
FUNCTIONAL GENOMICS OF THE PROTEIN KINASES AND PHOTOPHATASES OF MOUSE
Associate Advisor
Other advisors: Professor Brian Gabrielli
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2006
Doctor Philosophy
DYNAMIC IMAGING OF POST-GOLGI PROTEIN TRANSPORT
Associate Advisor
Other advisors: Professor Jennifer Stow
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2005
Doctor Philosophy
SHADES OF DOMAINS: BIOINFORMATIC IDENTIFICATION OF PROTEIN DOMAIN SUBTYPES AND CORRELATION WITH FUNCTIONAL SPECIFICITY
Associate Advisor
Other advisors: Professor David Hume
Media
Enquiries
Contact Associate Professor Rohan Teasdale directly for media enquiries about:
- Biology - cells
- Biology - host/pathogen interactions
- Cell biology
- Database mining - biology
- Endosomes
- Genome - human
- Host-Pathogen interactions
- Human genome
- Membrane trafficking - cell biology
- Pathogen-Host interactions
- Proteins
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