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
2023
Journal Article
Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts
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
2022
Journal Article
Multifaceted roles of retromer in EGFR trafficking and signaling activation
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
2021
Journal Article
De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex
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
2021
Journal Article
Retromer dependent changes in cellular homeostasis and Parkinson’s disease
Yang, Zhe, Li, Zebin and Teasdale, Rohan D. (2021). Retromer dependent changes in cellular homeostasis and Parkinson’s disease. Essays in Biochemistry, 65 (7), 987-998. doi: 10.1042/ebc20210023
2021
Journal Article
Formation of retromer transport carriers is disrupted by the Parkinson disease‐linked Vps35 D620N variant
Cui, Yi, Yang, Zhe, Flores‐Rodriguez, Neftali, Follett, Jordan, Ariotti, Nicholas, Wall, Adam A., Parton, Robert G. and Teasdale, Rohan D. (2021). Formation of retromer transport carriers is disrupted by the Parkinson disease‐linked Vps35 D620N variant. Traffic, 22 (4) tra.12779, 123-136. doi: 10.1111/tra.12779
2020
Journal Article
An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells
Ariotti, Nicholas, Wu, Yeping, Okano, Satomi, Gambin, Yann, Follett, Jordan, Rae, James, Ferguson, Charles, Teasdale, Rohan D., Alexandrov, Kirill, Meunier, Frederic A., Hill, Michelle M. and Parton, Robert G. (2020). An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells. Autophagy, 17 (9), 1-17. doi: 10.1080/15548627.2020.1820787
2019
Journal Article
Subcellular fractionation of HeLa cells for lysosome enrichment using a continuous Percoll-density gradient
Carosi, Julian M., Hattersley, Kathryn J., Cui, Yi, Yang, Zhe, Teasdale, Rohan D. and Sargeant, Timothy J. (2019). Subcellular fractionation of HeLa cells for lysosome enrichment using a continuous Percoll-density gradient. Bio-Protocol, 9 (18) e3362, e3362. doi: 10.21769/BioProtoc.3362
2019
Journal Article
Downregulation of SNX27 expression does not exacerbate amyloidogenesis in the APP/PS1 Alzheimer's disease mouse model
Milne, Michael R., Qian, Lei, Turnbull, Marion T., Kinna, Genevieve, Collins, Brett M., Teasdale, Rohan D. and Coulson, Elizabeth J. (2019). Downregulation of SNX27 expression does not exacerbate amyloidogenesis in the APP/PS1 Alzheimer's disease mouse model. Neurobiology of Aging, 77, 144-153. doi: 10.1016/j.neurobiolaging.2019.01.011
2019
Journal Article
Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities
Chandra, Mintu, Chin, Yanni K.-Y., Mas, Caroline, Feathers, J. Ryan, Paul, Blessy, Datta, Sanchari, Chen, Kai-En, Jia, Xinying, Yang, Zhe, Norwood, Suzanne J., Mohanty, Biswaranjan, Bugarcic, Andrea, Teasdale, Rohan D., Henne, W. Mike, Mobli, Mehdi and Collins, Brett M. (2019). Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities. Nature Communications, 10 (1) 1528, 1528. doi: 10.1038/s41467-019-09355-y
2019
Journal Article
A role of GCC88 in the retrograde transport of CI-M6PR and the maintenance of lysosomal activity
Cui, Yi, Yang, Zhe and Teasdale, Rohan D. (2019). A role of GCC88 in the retrograde transport of CI-M6PR and the maintenance of lysosomal activity. Cell Biology International, 43 (11) cbin.11118, 1234-1244. doi: 10.1002/cbin.11118
2018
Journal Article
Retromer has a selective function in cargo sorting via endosome transport carriers
Cui, Yi, Carosi, Julian M., Yang, Zhe, Ariotti, Nicholas, Kerr, Markus C., Parton, Robert G., Sargeant, Timothy J. and Teasdale, Rohan D. (2018). Retromer has a selective function in cargo sorting via endosome transport carriers. The Journal of Cell Biology, 218 (2), jcb.201806153-631. doi: 10.1083/jcb.201806153
2018
Journal Article
Structure of the membrane-assembled retromer coat determined by cryo-electron tomography
Kovtun, Oleksiy, Leneva, Natalya, Bykov, Yury S., Ariotti, Nicholas, Teasdale, Rohan D., Schaffer, Miroslava, Engel, Benjamin D., Owen, David. J., Briggs, John A. G. and Collins, Brett M. (2018). Structure of the membrane-assembled retromer coat determined by cryo-electron tomography. Nature, 561 (7724), 561-+. doi: 10.1038/s41586-018-0526-z
2018
Journal Article
Sorting Nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2
Yang, Zhe, Follett, Jordan, Kerr, Markus C., Clairfeuille, Thomas, Chandra, Mintu, Collins, Brett M. and Teasdale, Rohan D. (2018). Sorting Nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2. Journal of Biological Chemistry, 293 (18), 6802-6811. doi: 10.1074/jbc.RA117.000735
2017
Journal Article
The functional roles of retromer in Parkinson's disease
Cui, Yi, Yang, Zhe and Teasdale, Rohan D. (2017). The functional roles of retromer in Parkinson's disease. FEBS Letters, 592 (7), 1096-1112. doi: 10.1002/1873-3468.12931
2017
Journal Article
SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes
Tello-Lafoz, M., Rodríguez-Rodríguez, C., Kinna, G., Loo, L. S., Hong, W., Collins, B. M., Teasdale, R. D. and Mérida, I. (2017). SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes. Scientific Reports, 7 (1) 16361, 1-14. doi: 10.1038/s41598-017-16370-w
2017
Journal Article
SopB-mediated recruitment of SNX18 facilitates Salmonella typhimurium internalization by the host cell
Liebl, David, Qi, Xiaying, Zhe, Yang, Barnett, Timothy C. and Teasdale, Rohan D. (2017). SopB-mediated recruitment of SNX18 facilitates Salmonella typhimurium internalization by the host cell. Frontiers in Cellular and Infection Microbiology, 7 (JUN) 257. doi: 10.3389/fcimb.2017.00257
2017
Journal Article
Salmonella effector SopD2 interferes with Rab34 function
Teo, Wei Xuan, Yang, Zhe, Kerr, Markus Charles, Luo, Lin, Guo, Zhong, Alexandrov, Kirill, Stow, Jenny Lea and Teasdale, Rohan David (2017). Salmonella effector SopD2 interferes with Rab34 function. Cell Biology International, 41 (4), 433-446. doi: 10.1002/cbin.10739
2017
Journal Article
Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
Kerr, Markus C., Gomez, Guillermo A., Ferguson, Charles, Tanzer, Maria C., Murphy, James M., Yap, Alpha S., Parton, Robert G., Huston, Wilhelmina M. and Teasdale, Rohan D. (2017). Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis. Nature Communications, 8 (1) 14729, 14729. doi: 10.1038/ncomms14729
2017
Journal Article
Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
Paul, Blessy, Kim, Hyun Sung, Kerr, Markus C., Huston, Wilhelmina M., Teasdale, Rohan D. and Collins, Brett M. (2017). Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis. eLife, 6 (e22311) e22311, 1-23. doi: 10.7554/eLife.22311
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
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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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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Master Philosophy
Exploring the Role of Retromer-Associated Proteins and SNX-RGS Subfamily Proteins in Protein Trafficking
Principal Advisor
Other advisors: Dr Zhe Yang
Completed supervision
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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: Associate 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: Associate 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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