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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

41 - 53 of 53 works

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

Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli

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

Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins

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

SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection

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

A commensal gone bad: Complete genome sequence of the prototypical enterotoxigenic escherichia coli strain H10407

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

Autotransporters of Escherichia coli: A sequence-based characterization

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

Structural and functional characterization of three DsbA paralogues from Salmonella enterica serovar typhimurium

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

UpaH is a newly identified autotransporter protein that contributes to biofilm formation and bladder colonization by uropathogenic Escherichia coli CFT073

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

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

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

Identification and characterisation of novel autotransporters of enterohaemorrhagic escherichia coli O157:H7

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

EhaA is a novel autotransporter protein of enterohemorrhagic Escherichia coli O157:H7 that contributes to adhesion and biofilm formation

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

Autotransporter proteins: novel targets at the bacterial cell surface

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

Functional genomics of the regulation of nodule number in legumes

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.

Functional genomic analysis of nodule development in soybean and Lotus Japonicus

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

    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

    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

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

    Associate Advisor

    Other advisors: Professor Antje Blumenthal

  • 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

Completed supervision

Media

Enquiries

Contact Dr Timothy Wells directly for media enquiries about:

  • cystic fibrosis infections
  • Pseudomonas aeruginosa

Need help?

For help with finding experts, story ideas and media enquiries, contact our Media team:

communications@uq.edu.au