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Dr Timothy Wells
Dr

Timothy Wells

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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

Dr 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

  • 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.

  • 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

53 works between 2004 and 2024

21 - 40 of 53 works

2021

Journal Article

Antibody-dependent enhancement of bacterial disease: prevalence, mechanisms and treatment

Torres, Von Vergel L., Coggon, Carrie F. and Wells, Timothy J. (2021). Antibody-dependent enhancement of bacterial disease: prevalence, mechanisms and treatment. Infection and Immunity, 89 (4) e00054-21, 1-15. doi: 10.1128/IAI.00054-21

Antibody-dependent enhancement of bacterial disease: prevalence, mechanisms and treatment

2021

Journal Article

Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice

Moentadj, Rabia, Wang, Yiwen, Bowerman, Kate, Rehaume, Linda, Nel, Hendrik, O Cuiv, Paraic, Stephens, Juliette, Baharom, Amalina, Maradana, Muralidhara, Lakis, Vanessa, Morrison, Mark, Wells, Timothy, Hugenholtz, Philip, Benham, Helen, Le Cao, Kim-Anh and Thomas, Ranjeny (2021). Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice. Annals of the Rheumatic Diseases, 80 (5) annrheumdis-2020-219009, annrheumdis-2020. doi: 10.1136/annrheumdis-2020-219009

Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice

2020

Journal Article

Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization

Bryant, Jack Alfred, Morris, Faye C., Knowles, Timothy J., Maderbocus, Riyaz, Heinz, Eva, Boelter, Gabriela, Alodaini, Dema, Colyer, Adam, Wotherspoon, Peter J., Staunton, Kara A., Jeeves, Mark, Browning, Douglas F., Sevastsyanovich, Yanina R., Wells, Timothy J., Rossiter, Amanda E., Bavro, Vassiliy N., Sridhar, Pooja, Ward, Douglas G., Chong, Zhi-Soon, Goodall, Emily C. A., Icke, Christopher, Teo, Alvin, Chng, Shu-Sin, Roper, David I., Lithgow, Trevor, Cunningham, Adam F., Banzhaf, Manuel, Overduin, Michael and Henderson, Ian R. (2020). Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization. eLife, 9 e62614, 1-61. doi: 10.7554/elife.62614

Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization

2020

Conference Publication

A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. International Society for Heart and Lung Transplantation 40th Annual Meeting and Scientific Sessions, Online, 22 - 25 April 2020. Philadelphia, PA United States: Elsevier. doi: 10.1016/j.healun.2020.01.1265

A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

2020

Conference Publication

A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. 40th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT), Montreal, Canada, 22-25 April 2020. New York, NY United States: Elsevier.

A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation

2020

Journal Article

Treatment of life-threatening Pseudomonas aeruginosa infection by pheresis of inhibitory antibodies

Divithotawela, Chandima, Pham, Amy, Ledger, Emma L., Hopkins, Peter, Wells, Timothy J. and Chambers, Daniel (2020). Treatment of life-threatening Pseudomonas aeruginosa infection by pheresis of inhibitory antibodies. Journal of Heart and Lung Transplantation, 39 (1), 87-89. doi: 10.1016/j.healun.2019.10.001

Treatment of life-threatening Pseudomonas aeruginosa infection by pheresis of inhibitory antibodies

2019

Journal Article

Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

Benedikz, Elizabeth K., Bailey, Dalan, Cook, Charlotte N. L., Gonçalves-Carneiro, Daniel, Buckner, Michelle M. C., Blair, Jessica M. A., Wells, Timothy J., Fletcher, Nicola F., Goodall, Margaret, Flores-Langarica, Adriana, Kingsley, Robert A., Madsen, Jens, Teeling, Jessica, Johnston, Sebastian L., MacLennan, Calman A., Balfe, Peter, Henderson, Ian R., Piddock, Laura J. V., Cunningham, Adam F. and McKeating, Jane A. (2019). Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway. Scientific Reports, 9 (1) 7903. doi: 10.1038/s41598-019-44263-7

Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

2018

Journal Article

YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium

Morris, Faye C., Wells, Timothy J., Bryant, Jack A., Schager, Anna E., Sevastsyanovich, Yanina R., Squire, Derrick J. P., Marshall, Jennifer, Isom, Georgia L., Rooke, Jessica, Maderbocus, Riyaz, Knowles, Timothy J., Overduin, Michael, Rossiter, Amanda E., Cunningham, Adam F. and Henderson, Ian R. (2018). YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. Infection and Immunity, 86 (11) e00829-17. doi: 10.1128/IAI.00829-17

YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium

2018

Journal Article

A novel method of serum resistance by Escherichia coli that causes urosepsis

Coggon, Carrie F., Jiang, Andrew, Goh, Kelvin G. K., Henderson, Ian R., Schembri, Mark A. and Wells, Timothy J. (2018). A novel method of serum resistance by Escherichia coli that causes urosepsis. mBio, 9 (3) e00920-18, e00920-18. doi: 10.1128/mbio.00920-18

A novel method of serum resistance by Escherichia coli that causes urosepsis

2018

Journal Article

Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

Hammarlof, Disa L., Kroger, Carsten, Owen, Sian V., Canals, Rocio, Lacharme-Lora, Lizeth, Wenner, Nicolas, Schager, Anna E., Wells, Timothy J., Henderson, Ian R., Wigley, Paul, Hokamp, Karsten, Feasey, Nicholas A., Gordon, Melita A. and Hinton, Jay C. D. (2018). Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. Proceedings of the National Academy of Sciences of the United States of America, 115 (11), E2614-E2623. doi: 10.1073/pnas.1714718115

Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

2017

Journal Article

Antigen localization influences the magnitude and kinetics of endogenous adaptive immune response to recombinant Salmonella vaccines

Sevastsyanovich, Yanina R., Withers, David R., Marriott, Claire L., Morris, Faye C., Wells, Timothy J., Browning, Douglas F., Beriotto, Irene, Ross, Ewan, Ali, Hossam Omar, Wardius, Catherine A., Cunningham, Adam F., Henderson, Ian R. and Rossiter, Amanda E. (2017). Antigen localization influences the magnitude and kinetics of endogenous adaptive immune response to recombinant Salmonella vaccines. Infection and Immunity, 85 (12) e00593-17, e00593-17. doi: 10.1128/iai.00593-17

Antigen localization influences the magnitude and kinetics of endogenous adaptive immune response to recombinant Salmonella vaccines

2017

Conference Publication

Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis

Baillet, Athan, Bhuyan, Zaied Ahmed, Douillard, Claire, Bozon, Aurelie, Armitage, Charles, Romand, Xavier, Minh Vu Chuong Nguyen,, Favier, Bertrand, Wells, Timothy, Beagley, Kenneth and Thomas, Ranjeny (2017). Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis. 2017 ACR/ARHP Pediatric Rheumatology Symposium, San Diego, CA, United States, 3-8 November 2017. Hoboken, NJ, United States: John Wiley & Sons.

Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis

2015

Journal Article

Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion

Browning, Douglas F., Bavro, Vassiliy N., Mason, Jessica L., Sevastsyanovich, Yanina R., Rossiter, Amanda E., Jeeves, Mark, Wells, Timothy J., Knowles, Timothy J., Cunningham, Adam F., Donald, James W., Palmer, Tracy, Overduin, Michael and Henderson, Ian R. (2015). Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion. Molecular Microbiology, 97 (4), 646-659. doi: 10.1111/mmi.13052

Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion

2014

Journal Article

Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing

Wells, Timothy J., Whitters, Deborah, Sevastsyanovich, Yanina R., Heath, Jennifer N., Pravin, John, Goodall, Margaret, Browning, Douglas F., O'Shea, Matthew K., Cranston, Amy, De Soyza, Anthony, Cunningham, Adam F., MacLennan, Calman A., Henderson, Ian R. and Stockley, Robert A. (2014). Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. Journal of Experimental Medicine, 211 (9), 1893-1904. doi: 10.1084/jem.20132444

Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing

2013

Journal Article

Mutational and topological analysis of the Escherichia coli BamA protein

Browning, Douglas F., Matthews, Sophie A., Rossiter, Amanda E., Sevastsyanovich, Yanina R., Jeeves, Mark, Mason, Jessica L., Wells, Timothy J., Wardius, Catherine A., Knowles, Timothy J., Cunningham, Adam F., Bavro, Vassiliy N., Overduin, Michael and Henderson, Ian R. (2013). Mutational and topological analysis of the Escherichia coli BamA protein. PLoS ONE, 8 (12) e84512, e84512. doi: 10.1371/journal.pone.0084512

Mutational and topological analysis of the Escherichia coli BamA protein

2013

Journal Article

Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil

Franca, Fernanda L. S., Wells, Timothy J., Browning, Douglas F., Nogueira, Raquel Tayar, Sarges, Felipe Silva, Pereira, Ana Claudia, Cunningham, Adam F., Lucheze, Kely, Paula Rosa, Ana Claudia, Henderson, Ian R. and de Luna, Maria das Gracas (2013). Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil. PLoS ONE, 8 (7) e69971, e69971. doi: 10.1371/journal.pone.0069971

Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil

2013

Journal Article

Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis

Browning, Douglas F., Wells, Timothy J., Franca, Fernanda L. S., Morris, Faye C., Sevastsyanovich, Yanina R., Bryant, Jack A., Johnson, Matthew D., Lund, Peter A., Cunningham, Adam F., Hobman, Jon L., May, Robin C., Webber, Mark A. and Henderson, Ian R. (2013). Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis. Molecular Microbiology, 87 (5), 939-950. doi: 10.1111/mmi.12144

Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis

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

Type 1 and 5 secretion systems and associated toxins

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

A generalised module for the selective extracellular accumulation of recombinant proteins

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

Discovery of an archetypal protein transport system in bacterial outer membranes

Funding

Current funding

  • 2024 - 2025
    Counteracting cloaking antibodies to treat intractable Pseudomonas infection.
    Cystic Fibrosis Foundation USA
    Open grant
  • 2024 - 2025
    Evaluation of plasmapheresis to treat intractable lung infections in people with cystic fibrosis
    Cystic Fibrosis Research Limited
    Open grant
  • 2023 - 2025
    Personalising diagnosis and treatment of Pseudomonas aeruginosa infection (NHMRC Ideas Grant administered by Griffith University)
    Griffith University
    Open grant

Past funding

  • 2023 - 2024
    Understanding and counteracting antibody-mediated inflammation driving lung damage
    Conquer Cystic Fibrosis Lung Health Transplant Grant
    Open grant
  • 2022 - 2024
    Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds (an MSH-RSS administered by MSHHS)
    Metro South Research Support Scheme Co-funded Collaboration Grant
    Open grant
  • 2021 - 2024
    Impact and treatment of cloaking antibodies in Cystic Fibrosis
    Cystic Fibrosis Foundation USA
    Open grant
  • 2019 - 2021
    Paradoxical antibody: the role of antibody in exacerbating Pseudomonas lung infection
    NHMRC Project Grant
    Open grant
  • 2017
    Determining the scope and mechanism of inhibitory antibodies in bacterial lung infections.
    UQ Early Career Researcher
    Open grant

Supervision

Availability

Dr Timothy Wells is:
Available for supervision

Before you email them, read our advice on how to contact a supervisor.

Available projects

  • 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

  • Doctor Philosophy

    Investigating the gram-negative bacterial and host factors that drive sepsis outcomes

    Principal Advisor

    Other advisors: Dr Kate McCarthy

  • 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

  • Doctor Philosophy

    Investigating B cell responses to Pseudomonas O-Antigen

    Principal Advisor

    Other advisors: Professor Ian Henderson

  • Doctor Philosophy

    The role of cloaking antibodies in the pathophysiology, diagnosis, and treatment of inflammatory diseases

    Principal Advisor

    Other advisors: Professor Mark Morrison

  • Doctor Philosophy

    The impact of helpful and harmful immune responses on infection in the cystic fibrosis lung

    Principal Advisor

  • Master Philosophy

    Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds

    Principal Advisor

    Other advisors: Professor Kiarash Khosrotehrani

  • Doctor Philosophy

    Deciphering the protective program of innate and adaptive cells in pathogen infection

    Associate Advisor

    Other advisors: Professor Gabrielle Belz

  • Doctor Philosophy

    The role of endoplasmic reticulum stress in spondyloarthropathy

    Associate Advisor

    Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot

  • Doctor Philosophy

    Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculosis

    Associate Advisor

    Other advisors: Professor Antje Blumenthal

Completed supervision

Media

Enquiries

Contact Dr Timothy Wells directly for media enquiries about:

  • cystic fibrosis infections
  • Pseudomonas aeruginosa

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