Associate Professor Rohan Teasdale

Associate Professor

School of Biomedical Sciences
Faculty of Medicine

Affiliate Associate Professor

School of Chemistry and Molecular Biosciences
Faculty of Science
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.

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.
  • Retromer-dependent protein trafficking and adipocyte biology
    Adipose tissue, commonly referred to as fat, influences the function of nearly all other organ systems through secretion of a diverse range of metabolites and peptide hormones. In a nutrient-rich or fed state, high levels of insulin bind to its receptor on adipocytes and the resulting cell signaling events cause the translocation of GLUT4-specialised vesicles (GSV) to the plasma membrane. This results in an increased glucose uptake via the GLUT4 transporter. The formation of GSVs within adipocytes represents an important part of this interconnected metabolic system and is critical for its regulation. Using a series of novel cell line and mouse models, we are examining the contribution Retromer-dependent endosome protein sorting and formation of endosome-transport carriers has on the generation of GSVs in adipocytes and its impact on adipocyte biology within whole animal models.
  • Defining the role host cell membrane trafficking pathways play in pathogen infection
    In order to survive within the host cell, pathogens pirate the host cell’s membrane trafficking pathways to engineer intracellular niches, called inclusions. Using established molecular tools, in combination with sophisticated live-cell imaging technology, we will examine the membrane trafficking pathways hijacked by the pathogens. Our current research focuses on Salmonella typhimurium, a leading cause of human gastroenteritis, and Chlamydiae, the most prevalent cause of sexually transmitted disease.

Qualifications

  • Bachelor of Science(Hons), Monash University
  • PHD, Monash University

Publications

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.

View all Available Projects

Publications

Book Chapter

Journal Article

Conference Publication

  • Teasdale, R., Follett, J., Bugarcic, A., Yang, Z. and Collins, B. (2015). Parkinson-associated VPS35 mutations alter retromer cellular functions. In: Special Issue: 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. 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, (54-54). 23-27 August 2015. 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. In: ASCB Annual Meeting Abstracts. ASCB/IFCB Meeting, Philadelphia, PA United States, (). 06 - 10 December 2014.

  • 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. In: 22nd IUBMB Congress/37th FEBS Congress, Seville, Spain, (420-421). 4-9 September 2012. 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. In: William McLean and Tony Roberts, Proceedings of the 15th Computational Techniques and Applications Conference. CTAC2010 : 15th Biennial Computational Techniques and Applications Conference, Univeristy of New South Wales, Sydney, Australia, (C156-C171). 28 November - 1 December 2010. 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. In: Mikael Boden and Timothy Bailey, Conferences in research and practice in information technology online. 2006 Workshop on Intelligent Systems for Bioinformatics (WISB 2006). 2006 Workshop on Intelligent Systems for Bioinformatics (WISB 2006), Hobart, Australia, (67-72). 4/12/2006.

  • Sprenger, Josefine, Fink, J. Lynn and Teasdale, Rohan D. (2006). Evaluation and comparison of mammalian subcellular localization prediction methods. In: BMC bioinformatics. International Conference in Bioinformatics- InCoB2006, New Delhi, India, (1-7). 18-20 December, 2006. 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. In: H. P. Klinger and M. Schmid, Cytogenetic and Genome Research Vol. 101. Vertebrate Sex Determination, Kona, Hawaii, (261-265). 24-28 March, 2003. doi:10.1159/000074346

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

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.