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

Endosomal Dynamics and Neurodegeneration

The endosomal system of mammalian cells is a highly dynamic organelle, and the trafficking pathways associated with it are fundamental for a wide variety of cellular processes. We are developing cellular and computational approaches to identify novel mammalian proteins associated with the endosomal system including the retromer protein complex that is a central regulator of early endosome protein trafficking. Retromer has been recently implicated in both Alzheimer’s and Parkinson’s neurological diseases and we are investigating the molecular mechanisms underlying these diseases.

Research Interests

  • Protein trafficking in Disease
    The endosomal/lysosomal system of mammalian cells is a highly dynamic organelle and the trafficking pathways within the endosomal system are fundamental for a wide variety of key cellular processes. My research is focused on understanding how individual proteins are compartmentalized within the endosome/lysosomal system of the mammalian cell, and defining the protein machinery responsible for their organization and trafficking. The regulated movement of membrane receptors and ligands between the cell surface and intracellular compartments is vital to many cellular operations, including communication between cells and their environment. My research into defining the composition of a mammalian endosomal protein complex, termed the 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 PD. More broadly, endosomes are emerging to have a central role in the pathobiology of neurodegenerative diseases including Alzheimer’s & Parkinson’s disease.
  • Retromer’s role in neurological disease
    Retromer is responsible for coordinating protein trafficking from the endosomal compartment and pathogenetic mutations within a retromer subunit, Vps35, have been directly associated with causing late onset Parkinson’s disease (PD) . Recent reports show several point mutations of Vps35 cause late-onset PD. Reports implicating Vps35 in PD demonstrate a single point mutation of highly conserved amino acid 620 (Asp620Asn) in several families leads to an autosomal-dominant mode of PD inheritance. Further evidence for a link between retromer and sporadic PD is supported by the determination that retromer mRNA levels within the substantia nigra are significantly decreased in PD-affected patients. Indeed, in ongoing studies we have found that disruption of known retromer components contributes to the cellular pathology phenotypes associated with PD. We propose 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 our research is relevant to multiple progressive neurological disorders that are the most common causes of dementia.
  • Endosomal dynamics and pathogen invasion
    The endo-lysosomal system of mammalian cells incorporates highly dynamic endocytic membrane transport pathways that are fundamental for many cellular processes, including receptor signalling, uptake of essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Significantly, defects in endosomal trafficking are linked to many human diseases including various cancers, lysosomal storage diseases, neurodegenerative diseases and hypercholesterolemia. Furthermore, numerous infectious pathogens exploit specific endocytic pathways to invade the host. Characterisation of pathogen entry pathways is essential for understanding infectious diseases but has also proven to be a powerful tool for gaining insight into normal cellular processes. For example, to promote survival, Salmonella typhimurium subverts the host cell’s normal macropinocytic machinery to gain entry into the non-phagocytic epithelial cells of the intestinal wall. Once inside the cell, S. typhimurium actively alters the phosphoinositide composition of the enveloping macropinosome to avoid being delivered to the lysosome for destruction. Thus, S. typhimurium effectively manipulates the host cell’s membrane trafficking pathways in order to create a replicative niche within a customised macropinosome. Knowledge of the cell biology of these clinically important intracellular pathogens and how they interact with the host is incomplete. One of the most important and intriguing facets of endosomal function is the mechanism of biomolecular transport, both within the endosomal system and to and from other cellular organelles. It is essential that the cell precisely control the spatial and temporal trafficking of these numerous individual proteins. A predominant strategy exploited by intracellular pathogens is to disrupt these transport pathways to ensure survival by directly targeting host proteins involved in membrane transport and organisation of the endosome. My multi-disciplinary research group is focused on understanding how individual proteins are compartmentalized within the endo-lysosomal system in mammalian cells, and defining the protein machinery responsible for their organization and trafficking. We are currently investigating the molecular details of these host pathways and how they are modulated in response to numerous infectious intracellular bacteria. My current focus is Salmonella typhimurium, a leading cause of human gastroenteritis and Chlamydiae the most prevalent cause of sexually transmitted disease.
  • Defining the role host cell membrane trafficking pathways play in Chlamydial inclusion formation.
    Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen pirates the host’s membrane trafficking pathways to engineer an intracellular niche called an inclusion. In addition to providing a permissive environment, this strategy also shields the pathogen from the host’s immune system. Using established molecular tools in combination with sophisticated live cell imaging technology we will examine the membrane trafficking pathways hijacked by the pathogen and specifically key regulators of these pathways. Bacterial infectious diseases have an enormous impact on human health and survival. The essential host factors required for replication of intracellular pathogens constitute attractive drug targets. Their identification, characterization and subsequent structural studies will enable design and development of novel classes of anti-infective compounds.

Qualifications

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

Publications

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Supervision

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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.