Associate Professor Rohan Teasdale

Associate Professor

School of Biomedical Sciences
Faculty of Medicine
r.teasdale@uq.edu.au
+61 7 336 52319

Overview

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 Coordinator (BIOM6501/2 & BIOM6191/2)

BSc Cell Biology Major Convenor

BIOL2200 – Molecular Cell Biology I Lecturer and practical cooridinator

BIOL3006 – Molecular Cell Biology II Lecturer

BIOM2222 - Advanced Techniques in Biomedical Science Lecturer

Student Supervisor for Research Projects in Biomedical Sciences (SCIE3220/1 or Honours)

Research Interests

  • 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.
  • 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.
  • 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

Qualifications

  • Doctor of Philosophy, Monash University

Publications

  • Ng, Pei Ying, Ribet, Amy B. P., Guo, Qiang, Mullin, Benjamin H., Tan, Jamie W. Y., Landao-Bassonga, Euphemie, Stephens, Sébastien, Chen, Kai, Yuan, Jinbo, Abudulai, Laila, Bollen, Maike, Nguyen, Edward T. T. T., Kular, Jasreen, Papadimitriou, John M., Søe, Kent, Teasdale, Rohan D., Xu, Jiake, Parton, Robert G., Takayanagi, Hiroshi and Pavlos, Nathan J. (2023). Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts. Nature Communications, 14 (1) 906, 1-23. doi: 10.1038/s41467-023-36484-2

  • Yang, Zhe, Feng, Zhengyang, Li, Zebin and Teasdale, Rohan D. (2022). Multifaceted roles of retromer in EGFR trafficking and signaling activation. Cells, 11 (21) 3358, 1-17. doi: 10.3390/cells11213358

  • Chen, Kai-En, Guo, Qian, Hill, Timothy A., Cui, Yi, Kendall, Amy K., Yang, Zhe, Hall, Ryan J., Healy, Michael D., Sacharz, Joanna, Norwood, Suzanne J., Fonseka, Sachini, Xie, Boyang, Reid, Robert C., Leneva, Natalya, Parton, Robert G., Ghai, Rajesh, Stroud, David A., Fairlie, David P, Suga, Hiroaki, Jackson, Lauren P., Teasdale, Rohan D., Passioura, Toby and Collins, Brett M. (2021). De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex. Science Advances, 7 (49) eabg4007, eabg4007. doi: 10.1126/sciadv.abg4007

View all Publications

Supervision

View all Supervision

Available Projects

  • 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.

  • 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.

View all Available Projects

Publications

Book Chapter

  • Wang, Jack T. H., Kerr, Markus and Teasdale, Rohan D. (2014). Cancer insights through macropinocytosis: a role for sorting nexins?. The research and biology of Cancer I. (pp. 1-23) edited by iConcept Press. Hong Kong, China: iConcept Press.

  • Kerr, M. C., Castro, N. A., Karunaratne, S. and Teasdale, R. D. (2012). The phosphoinositides: key regulators of Salmonella containing vacuole (SCV) trafficking and identity. Salmonella - distribution, adaptation, control measures and molecular technologies. (pp. 251-264) edited by Bassam A. Annous and Joshua B. Gurtler. Rijeka, Croatia: InTech. doi: 10.5772/30761

  • Hamilton, Nicholas, Kerr, Markus, Burrage, Kevin and Teasdale, Rohan D. (2007). Analyzing real-time video microscopy: the dyamics and geometry of vescicles and tubules in endocytosis. Current Protocols in Cell Biology. (pp. 4.16.1-1.16.11) edited by Bonifacio, J. S., Dasso, M., Harford, J. B., Lippincott-Schwartz, J. and Yamada K. M.. Hoboken, NJ United States: John Wiley & Sons. doi: 10.1002/0471143030.cb0416s35

  • Stow, J. L. and Teasdale, R. D. (2005). Expression and localization of proteins in mammalian cells. Encyclopedia of Genetics, Genomics, Proteomics and Bioformatics. (pp. ---) edited by P S E Little and J S E Quackenbush. London, England: John Wiley & Sons. doi: 10.1002/047001153x.g208202

Journal Article

Conference Publication

  • 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.

  • 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

  • Follett, J., Norwood, S., Hamilton, N., Collins, B., Bugarcic, A. and Teasdale, R. D. (2014). Parkinson's Disease Causing Mutations Alters Retromer's Function. ASCB/IFCB Meeting, Philadelphia, PA United States, 06 - 10 December 2014. Bethesda, MD United States: American Society for Cell Biology.

  • Ghai, R., Mobli, M., Norwood, S. J., Bugarcic, A., Teasdale, R. D., King, G. F. and Collins, B. M. (2012). PX family proteins at the interface between intracellular trafficking and signalling. 22nd IUBMB Congress/37th FEBS Congress, Seville, Spain, 4-9 September 2012. Chichester, West Sussex, United Kingdom: Wiley-Blackwell. doi: 10.1111/j.1742-4658.2010.08705.x

  • Belward, John A., Burrage, Kevin, Teasdale, Rohan D. and Hamilton, Nicholas A. (2011). Linear models for endocytic transformations from live cell imaging. CTAC2010 : 15th Biennial Computational Techniques and Applications Conference, Univeristy of New South Wales, Sydney, Australia, 28 November - 1 December 2010. Cambridge, United Kingdom: Cambridge University Press. doi: 10.0000/anziamj.v52i0.3801

  • Hamilton, A, Pantelic, S, Hanson,, Fink, L, Karunaratne, M and Teasdale, R D (2006). Automated subcellar phenotype classification : An introduction and recent results. 2006 Workshop on Intelligent Systems for Bioinformatics (WISB 2006), Hobart, Australia, 4/12/2006. Sydney, Australia: Australian Computer Society.

  • Sprenger, Josefine, Fink, J. Lynn and Teasdale, Rohan D. (2006). Evaluation and comparison of mammalian subcellular localization prediction methods. International Conference in Bioinformatics- InCoB2006, New Delhi, India, 18-20 December, 2006. London: BioMed Central Ltd. doi: 10.1186/1471-2105-7-S5-S3

  • Bowles, J., Teasdale, R. D., James, K. M. and Koopman, P. A. (2003). Dppa3 is a marker of pluripotency and has a human homologue that is expressed in germ cell tumours. Vertebrate Sex Determination, Kona, Hawaii, 24-28 March, 2003. Basil, Switzerland: Karger. doi: 10.1159/000074346

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Master Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • 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.

  • 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.