
Overview
Background
Dr Timothy Wells joined the Frazer Institute in 2016 as a Senior Research Fellow. His research aims to find novel methods of treating multi-drug resistant bacteria, by examing the interactions between the host immune system and Gram negative bacteria. His research largely focuses on Pseudomonas aeruginosa acute and chronic infections, espeically in people living with cystic fibrosis. Dr Wells is passionate about making his research as clinically relevant as possible, with his work previously having led to novel treatment of critically ill patients. His research uses a mixture of molecular microbiology, immunology and genomic approaches.
Availability
- Associate Professor Timothy Wells is:
- Available for supervision
- Media expert
Qualifications
- Bachelor (Honours) of Biotechnology, The University of Queensland
- Doctor of Philosophy, The University of Queensland
Research interests
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Pseudomonas aeruginosa
The T-Wells lab is interested in all infections by Pseudomonas aeruginosa whether that be chronic lung infection, wound and joint infections, acute pneumonia, UTIs and bacteremia.
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Bacterial chronic lung infections
The T-Wells lab is interested in bacterial infections in people with cystic fibrosis, bronchiectasis, COPD and post-lung transplant
Research impacts
Dr Wells’s original work in the field of host- pathogen interactions during chronic lung infection has led to several key insights and direct translation to the clinic.
Antibody dependent enhancement of bacterial infection: Antibodies usually protect against bacterial infection, however Dr Wells' work has identified ‘cloaking antibodies’ in patients who have Pseudomonas aeruginosa infections. Cloaking antibodies paradoxically prevent immune killing of patient's bacterial strains. Importantly, high titres of cloaking antibodies has been associated with worse lung function and patient outcomes in people with cystic fibrosis, bronchiectasis and post-lung transplant. These antibodies are also prevelant in actue Pseduomonas infections such as bacteremia.
Novel treatment of multi-drug resistant Pseudomonas aeruginosa lung infection: As cloaking antibodies (cAbs) protect bacteria from immune killing, we hypothesised that cAb removal would restore normal immune killing. Three patients with chronic P. aeruginosa infections and cAb, who had exhausted all standard treatment options have now been treated via plasmapheresis. This treatment removes all antibody, including cAbs from the patients. After treatment, P. aeruginosa was undetectable in all patients, inflammatory markers were normal and lung function increased. As these patients had strains displaying resistance to many antibiotics used clinically, this is a novel treatment method for multi-drug resistant infections.
Works
Search Professor Timothy Wells’s works on UQ eSpace
2013
Book Chapter
Type 1 and 5 secretion systems and associated toxins
Wells, Timothy J. and Henderson, Ian R. (2013). Type 1 and 5 secretion systems and associated toxins. Escherichia coli: pathotypes and principles of pathogenesis. (pp. 499-532) edited by Michael S. Donnenberg. Cambridge, MA, United States: Academic Press. doi: 10.1016/B978-0-12-397048-0.00016-4
2012
Journal Article
A generalised module for the selective extracellular accumulation of recombinant proteins
Sevastsyanovich, Yanina R., Leyton, Denisse L., Wells, Timothy J., Wardius, Catherine A., Tveen-Jensen, Karina, Morris, Faye C., Knowles, Timothy J., Cunningham, Adam F., Cole, Jeffrey A. and Henderson, Ian R. (2012). A generalised module for the selective extracellular accumulation of recombinant proteins. Microbial Cell Factories, 11 (69) 69. doi: 10.1186/1475-2859-11-69
2012
Journal Article
Discovery of an archetypal protein transport system in bacterial outer membranes
Selkrig, Joel, Mosbahi, Khedidja, Webb, Chaille T., Belousoff, Matthew J., Perry, Andrew J., Wells, Timothy J., Morris, Faye, Leyton, Denisse L., Totsika, Makrina, Phan, Minh-Duy, Celik, Nermin, Kelly, Michelle, Oates, Clare, Hartland, Elizabeth L., Robins-Browne, Roy M., Ramarathinam, Sri Harsha, Purcell, Anthony W., Schembri, Mark A., Strugnell, Richard A., Henderson, Ian R., Walker, Daniel and Lithgow, Trevor (2012). Discovery of an archetypal protein transport system in bacterial outer membranes. Nature Structural and Molecular Biology, 19 (5), 506-510. doi: 10.1038/nsmb.2261
2012
Journal Article
Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli
Totsika, Makrina, Wells, Timothy J., Beloin, Christophe, Valle, Jaione, Allsopp, Luke P., King, Nathan P., Ghigo, Jean-Marc and Schembri, Mark A. (2012). Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli. Applied and Environmental Microbiology, 78 (7), 2179-2189. doi: 10.1128/AEM.06680-11
2011
Journal Article
Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins
Leyton, Denisse L., Sevastsyanovich, Yanina R., Browning, Douglas F., Rossiter, Amanda E., Wells, Timothy J., Fitzpatrick, Rebecca E., Overduin, Michael, Cunningham, Adam F. and Henderson, Ian R. (2011). Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins. Journal of Biological Chemistry, 286 (49), 42283-42291. doi: 10.1074/jbc.M111.306118
2011
Journal Article
SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection
Raghunathan, Dhaarini, Wells, Timothy J., Morris, Faye C., Shaw, Robert K., Bobat, Saeeda, Peters, Sarah E., Paterson, Gavin K., Jensen, Karina Tveen, Leyton, Denisse L., Blair, Jessica M. A., Browning, Douglas F., Pravin, John, Flores-Langarica, Adriana, Hitchcock, Jessica R., Moraes, Claudia T. P., Piazza, Roxane M. F., Maskell, Duncan J., Webber, Mark A., May, Robin C., MacLennan, Calman A., Piddock, Laura J., Cunningham, Adam F. and Henderson, Ian R. (2011). SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. Infection and Immunity, 79 (11), 4342-4352. doi: 10.1128/IAI.05592-11
2011
Journal Article
Spleen transcriptome response to infection with avian pathogenic <i>Escherichia coli</i> in broiler chickens
Sandford, Erin E., Orr, Megan, Balfanz, Emma, Bowerman, Nate, Li, Xianyao, Zhou, Huaijun, Johnson, Timothy J., Kariyawasam, Subhashinie, Liu, Peng, Nolan, Lisa K. and Lamont, Susan J. (2011). Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens. Bmc Genomics, 12 469. doi: 10.1186/1471-2164-12-469
2011
Journal Article
Comparative Genomics of Multidrug Resistance-Encoding IncA/C Plasmids from Commensal and Pathogenic <i>Escherichia coli</i> from Multiple Animal Sources
Fernandez-Alarcon, Claudia, Singer, Randall S. and Johnson, Timothy J. (2011). Comparative Genomics of Multidrug Resistance-Encoding IncA/C Plasmids from Commensal and Pathogenic Escherichia coli from Multiple Animal Sources. Plos One, 6 (8) e23415. doi: 10.1371/journal.pone.0023415
2011
Journal Article
Complete Genome Sequence of <i>Gallibacterium anatis</i> Strain UMN179, Isolated from a Laying Hen with Peritonitis
Johnson, Timothy J., Fernandez-Alarcon, Claudia, Bojesen, Anders Miki, Nolan, Lisa K., Trampel, Darrell W. and Seemann, Torsten (2011). Complete Genome Sequence of Gallibacterium anatis Strain UMN179, Isolated from a Laying Hen with Peritonitis. Journal of Bacteriology, 193 (14), 3676-3677. doi: 10.1128/JB.05177-11
2010
Journal Article
A commensal gone bad: Complete genome sequence of the prototypical enterotoxigenic escherichia coli strain H10407
Crossman, L. C., Chaudhuri, R. R., Beatson, S. A., Wells, T. J., Desvaux, M., Cunningham, A. F., Petty, N. K., Mahon, V., Brinkley, C., Hobman, J. L., Savarino, S. J., Turner, S. M., Pallen, M. J., Penn, C. W., Parkhill, J., Turner, A. K., Johnson, T. J., Thomson, N. R., Smith, S. G. J. and Henderson, I. R. (2010). A commensal gone bad: Complete genome sequence of the prototypical enterotoxigenic escherichia coli strain H10407. Journal of Bacteriology, 192 (21), 5822-5831. doi: 10.1128/JB.00710-10
2010
Journal Article
Autotransporters of Escherichia coli: A sequence-based characterization
Wells, Timothy J., Totsika, Makrina and Schembri, Mark A. (2010). Autotransporters of Escherichia coli: A sequence-based characterization. Microbiology, 156 (8), 2459-2469. doi: 10.1099/mic.0.039024-0
2010
Journal Article
Structural and functional characterization of three DsbA paralogues from Salmonella enterica serovar typhimurium
Heras, B, Totsika, M, Jarrott, R, Shouldice, SR, Guncar, G, Achard, MES, Wells, TJ, Argente, MP, McEwan, AG and Schembri, MA (2010). Structural and functional characterization of three DsbA paralogues from Salmonella enterica serovar typhimurium. Journal of Biological Chemistry, 285 (24), 18423-18432. doi: 10.1074/jbc.M110.101360
2010
Journal Article
Sequence Analysis and Characterization of a Transferable Hybrid Plasmid Encoding Multidrug Resistance and Enabling Zoonotic Potential for Extraintestinal <i>Escherichia coli</i>
Johnson, Timothy J., Jordan, Dianna, Kariyawasam, Subhashinie, Stell, Adam L., Bell, Nathan P., Wannemuehler, Yvonne M., Fernandez-Alarcon, Claudia, Li, Ganwu, Tivendale, Kelly A., Logue, Catherine M. and Nolan, Lisa K. (2010). Sequence Analysis and Characterization of a Transferable Hybrid Plasmid Encoding Multidrug Resistance and Enabling Zoonotic Potential for Extraintestinal Escherichia coli. Infection and Immunity, 78 (5), 1931-1942. doi: 10.1128/IAI.01174-09
2010
Journal Article
UpaH is a newly identified autotransporter protein that contributes to biofilm formation and bladder colonization by uropathogenic Escherichia coli CFT073
Allsopp, Luke P., Totsika, Makrina, Tree, Jai J., Ulett, Glen C., Mabbett, Amanda N., Wells, Timothy J., Kobe, Bostjan, Beatson, Scott A. and Schembri, Mark A. (2010). UpaH is a newly identified autotransporter protein that contributes to biofilm formation and bladder colonization by uropathogenic Escherichia coli CFT073. Infection and Immunity, 78 (4), 1659-1669. doi: 10.1128/IAI.01010-09
2009
Journal Article
The Escherichia coli O157:H7 EhaB autotransporter protein binds to laminin and collagen I and induces a serum IgA response in O157:H7 challenged cattle
Wells, Timothy J., McNeilly, Tom N., Totsika, Makrina, Mahajan, Arvind, Gally, David L. and Schembri, Mark A. (2009). The Escherichia coli O157:H7 EhaB autotransporter protein binds to laminin and collagen I and induces a serum IgA response in O157:H7 challenged cattle. Environmental Microbiology, 11 (7), 1803-1814. doi: 10.1111/j.1462-2920.2009.01905.x
2008
Other Outputs
Identification and characterisation of novel autotransporters of enterohaemorrhagic escherichia coli O157:H7
Wells, Timothy (2008). Identification and characterisation of novel autotransporters of enterohaemorrhagic escherichia coli O157:H7. PhD Thesis, School of Chemistry and Molecular Bioscience, The University of Queensland. doi: 10.14264/178070
2008
Journal Article
EhaA is a novel autotransporter protein of enterohemorrhagic Escherichia coli O157:H7 that contributes to adhesion and biofilm formation
Wells, T.J., Sherlock, O., Rivas, L., Mahajan, A., Beatson, S.A., Torpdahl, M., Webb, R.I., Allsopp, L., Gobius, K., Gally, D.L. and Schembri, M.A. (2008). EhaA is a novel autotransporter protein of enterohemorrhagic Escherichia coli O157:H7 that contributes to adhesion and biofilm formation. Environmental Microbiology, 10 (3), 589-604. doi: 10.1111/j.1462-2920.2007.01479.x
2007
Journal Article
Autotransporter proteins: novel targets at the bacterial cell surface
Wells, T. J., Tree, J. J., Ulett, G. C. and Schembri, M. A. (2007). Autotransporter proteins: novel targets at the bacterial cell surface. Fems Microbiology Letters, 274 (2), 163-172. doi: 10.1111/j.1574-6968.2007.00833.x
2005
Conference Publication
Functional genomics of the regulation of nodule number in legumes
Gresshoff, PM, Gualtieri, G, Laniya, T, Indrasumunar, A, Miyahara, A, Nontachaiyapoom, S, Wells, T, Biswas, B, Chan, PK, Scott, P, Kinkema, M, Djordjevic, M, Hoffmann, D, Pregelj, L, Buzas, DM, Li, DX, Men, A, Jiang, Q, Hwang, CH and Carroll, BJ (2005). Functional genomics of the regulation of nodule number in legumes. 14th International Nitrogen Fixation Congress, Beijing, China, 27 October - 1 November 2004. The Netherlands: Springer. doi: 10.1007/1-4020-3570-5
2004
Conference Publication
Functional genomic analysis of nodule development in soybean and Lotus Japonicus
Gresshoff, P. M., Carroll, B. J., Gualtieri Gonzalez, G. S., Vickers, C., Kuen, P., Huang, C., Scott, P. T., Kinkema, M. D., Men, A., Stiller, J., Jiang, Q., Laniya, T.S., Buzas, D. M., Miyahara, A., Indrasumunar, A., Nontachaiyapoom, S., Hoffmann, D., Biswas, B., Wells, T. J., So, H., Pregelj, L. and Dong, X. (2004). Functional genomic analysis of nodule development in soybean and Lotus Japonicus. Com Bio 2004, Intercontinental Burswood Resort, Perth, Australia, 26-30 September, 2004.
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Timothy Wells is:
- Available for supervision
Before you email them, read our advice on how to contact a supervisor.
Available projects
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Synergistic drugs to counteract cloaking antibodies
Some patients infected with P. aeruginosa produce antibodies that, instead of fighting infection, actively protect P. aeruginosa from killing by the immune system. These ‘cloaking antibodies’ (cAb) target a lipopolysaccharide on the bacterial surface, known as O-antigen and form a physical barrier that stops the membrane attack complex (MAC) from reaching the bacterial outer membrane. Importantly, patients with cAb had greater disease severity and worse outcomes than patients with no cAb. Previous treatment for cAbs has focused on removal of the antibody, however a second attractive target is the infecting bacteria itself. We have recently investigated the bacterial requirements for the cloaking phenotype by creating strains with variable amounts and lengths of O-antigen expression. Serum bactericidal assays revealed that the serum-inhibition phenotype requires long and dense O-antigen We hypothesise that existing bacterial outer membrane modifying drugs can overcome the effect of cAbs, without cAb removal. This project will investigate potential synergistic drugs that could counteract cAbs, leading to bacterial killing.
Supervision history
Current supervision
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Master Philosophy
Antibody-mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds
Principal Advisor
Other advisors: Professor Kiarash Khosrotehrani
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Doctor Philosophy
The impact of helpful and harmful immune responses on infection in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
The role of Two Partner Secretion proteins in the virulence of Pseudomonas aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson, Dr Jessica Rooke
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Doctor Philosophy
Investigating the gram-negative bacterial and host factors that drive sepsis outcomes
Principal Advisor
Other advisors: Dr Kate McCarthy
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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistance in the cystic fibrosis lung
Principal Advisor
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Master Philosophy
Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds
Principal Advisor
Other advisors: Professor Kiarash Khosrotehrani
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Doctor Philosophy
The Role of PlpD in the Virulence of P. aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson, Dr Jessica Rooke
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Doctor Philosophy
Improving Plasmapheresis: Investigating specific removal of cloaking antibodies to treat Pseudomonas aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson
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Doctor Philosophy
The role of cloaking antibodies in the pathophysiology, diagnosis, and treatment of inflammatory diseases
Principal Advisor
Other advisors: Professor Mark Morrison
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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistance in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistence in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
Targeting the outer membrane of Pseudomonas aeruginosa to disrupt the action of cloaking antibodies in cystic fibrosis
Principal Advisor
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Doctor Philosophy
Investigating B cell responses to Pseudomonas O-Antigen
Principal Advisor
Other advisors: Professor Ian Henderson
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Doctor Philosophy
High Mobility Group Box Family Member TOX2 in Innate Lymphoid Cell Development and Maintenance
Associate Advisor
Other advisors: Professor Gabrielle Belz
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Doctor Philosophy
Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculosis
Associate Advisor
Other advisors: Professor Antje Blumenthal
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Doctor Philosophy
Deciphering the protective program of innate and adaptive cells in pathogen infection
Associate Advisor
Other advisors: Professor Gabrielle Belz
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Doctor Philosophy
The Role of Endoplasmic Reticulum Stress in Autoimmune Inflammatory Arthritis
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
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Doctor Philosophy
The role of endoplasmic reticulum stress in spondyloarthropathy
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
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Doctor Philosophy
The Role of Endoplasmic Reticulum Stress in Autoimmune Inflammatory Arthritis
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
Completed supervision
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2025
Doctor Philosophy
Investigating Pseudomonas aeruginosa persistence in the cystic fibrosis lung
Principal Advisor
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2023
Doctor Philosophy
Antibody-Dependent Serum Resistance of Intractable Lung Bacteria
Principal Advisor
Other advisors: Professor Dan Chambers
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2021
Doctor Philosophy
Mechanisms Underpinning Antibody-Mediated Serum Resistance of Gram-Negative Bacteria
Principal Advisor
Other advisors: Professor Mark Morrison
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2025
Doctor Philosophy
The Role of Endoplasmic Reticulum Stress in Autoimmune Inflammatory Arthritis
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
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2024
Doctor Philosophy
Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculo sis
Associate Advisor
Other advisors: Professor Antje Blumenthal
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2023
Doctor Philosophy
Investigating immunosuppression and immunotherapy in bacterial infection
Associate Advisor
Other advisors: Associate Professor Fernando Guimaraes
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2023
Doctor Philosophy
Immune functions of WNT production and signalling in the host response to infection with pathogenic E. coli.
Associate Advisor
Other advisors: Dr Janin Chandra, Professor Antje Blumenthal
Media
Enquiries
Contact Associate Professor Timothy Wells directly for media enquiries about:
- cystic fibrosis infections
- Pseudomonas aeruginosa
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