Biosecurity Research Program and Training Centre

The Gulbali Biosecurity Research program (C2B) studies viral and host proteins' traffic to the nucleus, crucial for targeting pathogenic viruses, enhancing cancer therapies, and understanding immune responses. Our research uses structural biology, gene cloning, protein crystallography, and biochemical assays to explore new therapeutic avenues.

The challenge

The Biosecurity program exists to investigate and understand various aspects of viral proteins, host proteins, and immune responses. By utilising techniques such as structural biology, gene cloning, and protein crystallography, the program aims to uncover new insights and potential therapies for pathogenic viruses, cancer, and immune-related diseases.

Funding: Department of Agriculture, Fisheries and Forestry (DAFF) $9M to establish a Biosecurity Training Centre (BTC).

Our response

The purpose of the program is to advance scientific knowledge and develop new avenues for therapies in the fields of virology, immunology, and cancer research. The plan involves utilising techniques like structural biology, gene cloning, protein crystallography, mutagenesis, and biochemical assays to study viral proteins, host proteins, and immune responses. The project aims to understand how pathogenic viruses inhibit immune responses and explore potential targets for intervention. Additionally, it involves investigating vaccine development, overcoming bacterial drug resistance, and studying the role of specific proteins in developmental biology and cancer.

The goal

The program aims to achieve several goals:

Understand how pathogenic viruses suppress the innate immune response: By studying specific viral proteins from various viruses, such as Ebola, MERS, Hendra, Nipah, Dengue, Zika, Rabies, and others, the project aims to unravel the mechanisms by which these viruses inhibit the innate immune response.
Develop new avenues for therapies: Through structural biology, gene cloning, protein crystallography, mutagenesis, and biochemical assays, the project seeks to establish novel approaches for targeting pathogenic viruses and enhancing cancer therapies.
Investigate vaccine development: The project includes research on developing vaccines for beak and feather disease virus, which could have significant implications for avian health.
Overcome bacterial drug resistance: Research projects focus on developing dual enzyme inhibitors to combat bacterial drug resistance, potentially leading to more effective treatment options.
Study the role of SOX proteins in developmental biology and cancer: The project explores the involvement of SOX proteins in both developmental biology and cancer, aiming to deepen our understanding of their functions and implications for disease.

Overall, the project aims to contribute to our understanding of viral-host interactions, immune responses, and disease mechanisms, with the ultimate goal of improving therapeutic strategies and medical interventions.

Our team

Principal scientist

Professor Jade Forwood

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Our research team

Dr Justin Roby

Virologist and Innate Immunologist

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Dr Gayle Petersen

Molecular Biologist

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Dr Babu Nath

Molecular Biologist

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Dr Suman Gupta

Veterinary Epidemiology, Biosecurity and Surveillance

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Dr Jeffrey Nanson

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Dr Crystall Swarbrick

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Dr Renate Schwab

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Dr Joanne Millar

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Dr Richard Culas

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Dr Jane Kelly

Livestock production

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Dr Marta Hernandez-Jover

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Dr Shane Raidal

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Dr Shubho Das

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Dr Jessica Tout-Lyon

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Professor Leslie Weston

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Associate Professor Jane Heller

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Our research students

Emily Cross

PhD Student Topic: Understanding mechanisms of nuclear transport during viral infection

Camilla Donnelly

PhD Student Topic: Structural analysis of protein-protein interactions involved in pathogenesis and viral replication of Lyssaviruses and Henipaviruses

Jennifer Hawker

PhD Student Topic: Structural and molecular mechanisms of NSs-mediated pathogenesis of bunyaviruses.

Mikayla Hoad

PhD Student Topic: The structural mechanisms between Adeno Associated Viruses and host proteins for nuclear Localization

Thilini Munasinghe

PhD Student Topic: Structural analysis of ORF4b protein

Paige Taylor

PhD Student Topic: Investigating the molecular determinants for pathogenicity of Influenza A, primarily in its interaction with ANP32A through structural elucidation.

Emily Wagon

Honours Student Topic: Investigation of two newly emerged henipaviruses: comparing how the Langya virus and Angavokely virus matrix proteins interact with host cell nuclear import molecules.

Key research publications

Publications

MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity. TS Munasinghe, MR Edwards, S Tsimbalyuk, OA Vogel, KM Smith, M Stewart, JK Foster, LA Bosence, D Aragão, JA Roby, CF Basler, JK Forwood. Nature communications. 2022. Accepted. In press. [Impact Factor 17.7]
Structural basis for nuclear import selectivity of the pioneer transcription factor SOX2. B Jagga, M Edwards, M Pagin, KM Wagstaff, D Aragão, N Roman, JD Nanson, SR Raidal, N Dominado, M Stewart, DA Jans, GR Hime, SK Nicolis, CF Basler, JK Forwood. Nature communications. 2021 Jan 4;12(1):28. doi: 10.1038/s41467-020-20194-0. [Impact Factor 17.7]
Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses. KM Smith, S Tsimbalyuk, MR Edwards, EM Cross, J Batra, TPS da Costa, D Aragão, CF Basler, JK Forwood. Nature communications. 9 (1), 3703. 2018 Sep 12;9(1):3703. doi: 10.1038/s41467-018-05928-5. [Impact Factor 17.7]
Sarker S, Terrón M.C, Khandokar Y, Aragão, D, Hardy, J.M, Radjainia M, Jiménez-Zaragoza M, Pablo PJ, Coulibaly F, Luque Buzo D, Raidal, S.R., Forwood J.K. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nature Communications. 2016 Oct 4;7:13014. doi: 10.1038/ncomms13014 [Impact Factor 17.7]
In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting. Tu WJ, Melino M, Dunn J, McCuaig RD, Bielefeldt-Ohmann H, Tsimbalyuk S, Forwood JK, Ahuja T, Vandermeide J, Tan X, Tran M, Nguyen Q, Zhang L, Nam A, Pan L, Liang Y, Smith C, Lineburg K, Nguyen TH, Sng JDJ, Tong ZWM, Chew KY, Short KR, Le Grand R, Seddiki N, Rao S. Nature Communications. 2023 Jun 27;14(1):3680. doi: 10.1038/s41467-023-39341-4. [Impact Factor 17.7]
Forwood JK, Thakur AS, Guncar G, Marfori M, Mouradov D, Meng W, Robinson J, Huber T, Kellie S, Martin JL, Hume DA, Kobe B. Structural basis for recruitment of tandem hotdog domains in acyl-CoA thioesterase 7 and its role in inflammation. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(25):10382-10387. [Impact Factor 12.8]
Swarbrick CMD, Nanson JD, Patterson EI, Forwood JK. Structure, function, and regulation of thioesterases. Progress in Lipid Research. 2020 Jul;79:101036. doi: 10.1016/j.plipres.2020.101036. Epub 2020 May 19. PMID: 32416211 [Impact Factor 14.6]
Kirkby B, Roman N, Kobe B, Kellie S, Forwood JK. Functional and Structural Properties of Mammalian Acyl-Coenzyme A Thioesterases. Progress in Lipid Research. 2010; 49(4):366-77. [Impact Factor 14.6]
Harley VR, Layfield S, Mitchell CL, Forwood JK, John AP, Briggs LJ, McDowall SG, Jans DA. Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proceeding of the National Academy of Sciences U.S.A. 2003; 100(12):7045-7050. [Impact Factor 12.8]
Wang CA, Guncar G, Forwood JK, Teh T, Catanzariti A, Schirra H, Anderson PA, Ellis JG, Dodds PN, Kobe B. Crystal structures of flax rust avirulence proteins AvrL567-A and AvrL567–D reveal the structural basis for flax disease resistance specificity. Plant Cell 2007; 19(9):2898-2912. [Impact Factor 12.1]