
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
2004
Journal Article
Identifying the molecular phenotype of renal progenitor cells
Challen, G. A., Martinez, G., Davis, M. J., Taylor, D. F., Crowe, M., Teasdale, R. D., Grimmond, S. M. and Little, M. H. (2004). Identifying the molecular phenotype of renal progenitor cells. Journal of The American Society of Nephrology, 15 (9), 2344-2357. doi: 10.1097/01.ASN.0000136779.17837.8F
2004
Journal Article
Expression of the tudor-related gene Tdrd5 during development of the male germline in mice
Smith, J. M., Bowles, J., Wilson, M., Teasdale, R. D. and Koopman, P. (2004). Expression of the tudor-related gene Tdrd5 during development of the male germline in mice. Gene Expression Patterns, 4 (6), 701-705. doi: 10.1016/j.modgep.2004.04.002
2004
Journal Article
Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma imembrane following EGF stimulation
Merino-Trigo, A., Kerr, M. C., Houghton, F., Lindberg, A., Mitchell, C., Teasdale, R. D. and Gleeson, P. A. (2004). Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma imembrane following EGF stimulation. Journal of Cell Science, 117 (26), 6413-6424. doi: 10.1242/jcs.01561
2004
Journal Article
SVMtm: Support vector machines to predict transmembrane segments
Yuan, Z., Mattick, J. S. and Teasdale, R. D. (2004). SVMtm: Support vector machines to predict transmembrane segments. Journal of Computational Chemistry, 25 (5), 632-636. doi: 10.1002/jcc.10411
2004
Journal Article
Identification of a Golgi-localised GRIP domain protein from Arabidopsis thaliana
Gilson, Paul R., Vergara, Claudia E., Kjer-Nielsen, Lars, Teasdale, Rohan D., Bacic, Antony and Gleeson, Paul A. (2004). Identification of a Golgi-localised GRIP domain protein from Arabidopsis thaliana. Planta, 219 (6), 1050-1056. doi: 10.1007/s00425-004-1311-9
2003
Journal Article
Intracellular sorting and transport of proteins
van Vliet, Catherine, Thomas, Elaine C., Merino-Trigo, Ana, Teasdale, Rohan D. and Gleeson, Paul A. (2003). Intracellular sorting and transport of proteins. Progress in Biophysics and Molecular Biology, 83 (1), 1-45. doi: 10.1016/S0079-6107(03)00019-1
2003
Journal Article
Analysis of the mouse transcriptome for genes involved in the function of the nervous system
Gustincich, Stefano, Batalov, Serge, Beisel, Kirk W., Bona, Hidemasa, Carninci, Piero, Fletcher, Colin F., Grimmond, Sean, Hirokawa, Nobutaka, Jarvis, Erich D., Jegla, Tim, Kawasawa, Yuka, LeMieux, Julianna, Miki, Harukata, Raviola, Elio, Teasdale, Rohan D., Tominaga, Naoko, Yagi, Ken, Zimmer, Andreas, RIKEN GER Group, GSL Members, Hayashizaki, Yoshihide and Okazaki, Yasushi (2003). Analysis of the mouse transcriptome for genes involved in the function of the nervous system. Genome Research, 13 (6B), 1395-1401. doi: 10.1101/gr.1135303
2003
Journal Article
Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome
Tajul Arifin, K., Teasdale, R. D., Ravasi, T., Hume, D. A., RIKEN GER Group,, GSL Members, and Mattick, J. S. (2003). Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome. Genome Reaserch, 13 (6B), 1416-1429. doi: 10.1101/gr.1015703
2003
Journal Article
Mouse proteome analysis
Kanapin, A., Batalov, S., Davis, M., Gough, J., Grimmond, S. M., Kawaji, H., Magrane, M., Matsuda, H., Schonbach, C., Teasdale, R. D., RIKEN GER Group,, GSL Members, and Yuan, Z. (2003). Mouse proteome analysis. Genome Research, 13 (6B), 1335-1344. doi: 10.1101/gr.978703
2003
Journal Article
Computational differentiation of N-terminal signal peptides and transmembrane helices
Yuan, Z., Davis, M. J., Zhang, F. S. and Teasdale, R. D. (2003). Computational differentiation of N-terminal signal peptides and transmembrane helices. Biochemical And Biophysical Research Communications, 312 (4), 1278-1283. doi: 10.1016/j.bbrc.2003.11.069
2003
Journal Article
Genomic screen for genes involved in mammalian craniofacial development
Fowles, L. F., Bennetts, J. S., Berkman, J. L., Williams, E., Koopman, P., Teasdale, R. D. and Wicking, C. (2003). Genomic screen for genes involved in mammalian craniofacial development. Genesis, 35 (2), 73-87. doi: 10.1002/gene.10165
2003
Journal Article
Contextual binding of p120ctn to E-cadherin at the basolateral plasma membrane in polarized epithelia
Miranda, K. C., Joseph, S. R., Yap, A. S., Teasdale, R. D. and Stow, J. L. (2003). Contextual binding of p120ctn to E-cadherin at the basolateral plasma membrane in polarized epithelia. Journal of Biological Chemistry, 278 (44), 43480-43488. doi: 10.1074/jbc.M305525200
2003
Journal Article
The mouse secretome: functional classification of the proteins secreted into the extracellular environment
Grimmond, Sean M., Miranda, Kevin C., Yuan, Zheng, Davis, Melissa J., Hume, David A., Yagi, Ken, Tominaga, Naoko, Bono, Hidemasa, Hayashizaki, Yoshihide, Okazaki, Yasushi, RIKEN GER Group,, GSL Members, and Teasdale, Rohan D. (2003). The mouse secretome: functional classification of the proteins secreted into the extracellular environment. Genome Research, 13 (6B), 1350-1359. doi: 10.1101/gr.983703
2003
Conference Publication
Dppa3 is a marker of pluripotency and has a human homologue that is expressed in germ cell tumours
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
2002
Journal Article
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs
Teasdale, R. D., Hume, D. A., Yuan, Zheng and The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I & II Team (2002). Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature, 420 (6915), 563-573. doi: 10.1038/nature01266
2002
Journal Article
Secretory pathway of trypanosomatid parasites
McConville, Malcolm J., Mullin, Kylie A., Ilgoutz, Steven C. and Teasdale, Rohan D. (2002). Secretory pathway of trypanosomatid parasites. Microbiology and Molecular Biology Reviews, 66 (1), 122-154. doi: 10.1128/MMBR.66.1.122-154.2002
2002
Journal Article
Genes induced by growth hormone in a model of adipogenic differentiation
Shang, C. A., Thompson, B. J. L., Teasdale, R., Brown, R. J. and Waters, M. J. (2002). Genes induced by growth hormone in a model of adipogenic differentiation. Molecular and Cellular Endocrinology, 189 (1-2), 213-219. doi: 10.1016/S0303-7207(01)00590-1
2002
Journal Article
Twenty pairs of Sox: Extent, homology, and nomenclature of the mouse and human sox transcription factor gene families
Schepers, GE, Teasdale, RD and Koopman, P (2002). Twenty pairs of Sox: Extent, homology, and nomenclature of the mouse and human sox transcription factor gene families. Developmental Cell, 3 (2), 167-170. doi: 10.1016/S1534-5807(02)00223-X
2002
Journal Article
Targeting of the GRIP domain to the trans-Golgi network is conserved from protists to animals
McConville, M. J., Ilgoutz, S. C., Teasdale, R. D., Foth, B. J., Matthews, A., Mullin, K. A. and Gleeson, P A. (2002). Targeting of the GRIP domain to the trans-Golgi network is conserved from protists to animals. European Journal of Cell Biology, 81 (9), 485-495. doi: 10.1078/0171-9335-00268
2002
Journal Article
The Phox Homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation
Cozier, G. E., Carlton, J., McGregor, A. H., Gleeson, P. A., Teasdale, B. D., Mellor, H. and Cullen, P. J. (2002). The Phox Homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. Journal of Biological Chemistry, 277 (50), 48730-48736. doi: 10.1074/jbc.M206986200
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Rohan Teasdale is:
- Available for supervision
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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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Doctor Philosophy
Dissecting the role of retrograde trafficking machineries within the mammalian endosomal system
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
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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
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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