Professor Alexander Khromykh

Professor

School of Chemistry and Molecular Biosciences
Faculty of Science

Overview

Alexander Khromykh has PhD degree in Molecular Virology. He worked as Postdoctoral Fellow at the University of Ottawa in Canada. He then joined Sir Albert Sakzewski Virus Research Centre in Brisbane and became a laboratory Head in 2001. He moved his laboratory to St Luica campus in 2005 to take an appointment with the School of Chemistry and Molecular Biosciences (SCMB). He was the founding Director of the SCMB’s Centre for Infectious Disease Research and is currently the Deputy Director of the Australian Infectious Diseases Research Centre. He is also the Director of Centre of Excellence and a member of COVID-19 and Zika virus Task Forces in the Global Virus Network.

Research Interests

  • Molecular pathogenesis of RNA viruses
    Viruses of main interest include West Nile virus, Zika virus and SARS-CoV-2 virus. A particular strength is in the developing infectious clones and replicons and utilising them to study virus replication, to identify viral determinants of pathogenicity and to develop vaccines and antivirals.
  • Evasion of host antiviral response by pathogenic RNA viruses
    We apply advanced molecular methodologies including screening with viral RNAi libraries to identify new host antiviral genes and to dissect mechanisms employed by pathogenic RNA viruses to evade antiviral responses.
  • The role of viral and host noncoding RNAs in virus-host interaction
    We study biogenesis of novel viral noncoding RNAs and elucidate mechanisms by which both, viral and host noncoding RNAs shape the outcomes of infection with pathogenic RNA viruses.

Research Impacts

The main areas of research of the group are molecular virology, viral pathogenesis, and virus-host interactions. The viruses studied in the group are pathogenic RNA viruses, viruses such as West Nile virus, Zika virus, and SARS-CoV-2 virus. The goal of the research is to determine the mechanisms by which these viruses cause disease in the hosts and to identify viral and host factors determining the outcome of infection. The group uses a range of classical and more modern approaches including molecular manipulations with viral infectious cDNA clones and replicons, transient and stable expression of viral proteins and noncoding RNAs, viral replication and virulence assays, deep mutational scanning, mass spectrometry, next generation sequencing, siRNA knockdowns, and knockout cells and mice. Together, these approaches allow the group to perform detailed analysis of the effects of changes in the viral and host genomes that are likely to have a profound impact on virus replication and pathogenesis. The obtained knowldge is also applied to develop novel vaccine platforms and test antivirals.

Qualifications

  • Bachelor of Science, Tomsk State University
  • Doctor of Philosophy, The Institute for Molecular Virology

Publications

  • Peng, Nias Y. G., Amarilla, Alberto A., Hugo, Leon E., Modhiran, Naphak, Sng, Julian D. J., Slonchak, Andrii, Watterson, Daniel, Setoh, Yin Xiang and Khromykh, Alexander A. (2022). The distinguishing NS5-M114V mutation in American Zika virus isolates has negligible impacts on virus replication and transmission potential. PLOS Neglected Tropical Diseases, 16 (5) e0010426, e0010426. doi: 10.1371/journal.pntd.0010426

  • Shalash, Ahmed O., Azuar, Armira, Madge, Harrison Y. R., Modhiran, Naphak, Amarilla, Alberto A., Liang, Benjamin, Khromykh, Alexander A., Hussein, Waleed M., Chappell, Keith J., Watterson, Daniel, Young, Paul R., Skwarczynski, Mariusz and Toth, Istvan (2022). Peptide-based vaccine against SARS-CoV-2: peptide antigen discovery and screening of adjuvant systems. Pharmaceutics, 14 (4) 856, 856. doi: 10.3390/pharmaceutics14040856

  • McMillan, Christopher L. D., Azuar, Armira, Choo, Jovin J. Y., Modhiran, Naphak, Amarilla, Alberto A., Isaacs, Ariel, Honeyman, Kate E., Cheung, Stacey T. M., Liang, Benjamin, Wurm, Maria J., Pino, Paco, Kint, Joeri, Fernando, Germain J. P., Landsberg, Michael J., Khromykh, Alexander A., Hobson-Peters, Jody, Watterson, Daniel, Young, Paul R. and Muller, David A. (2022). Dermal delivery of a SARS-CoV-2 subunit vaccine induces immunogenicity against variants of concern. Vaccines, 10 (4) 578, 578. doi: 10.3390/vaccines10040578

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Supervision

View all Supervision

Available Projects

  • This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

    Flaviviruses are important human pathogens that include West Nile, Dengue, Zika, Yellow fever virus and other viruses. They have a unique ability to produce viral noncoding RNA from their 3' untranslated region by hijacking host exoribonuclease. This RNA, termed subgenomic flaviviral RNA (sfRNA), accumulates in infected cells in high abundance and facilitates viral pathogenesis by supressing antiviral response. However, the molecular mechanism that determines this activity is not fully elucidated. Recently we have discovered that sfRNA of Zika virus executes this function in cooperation with the viral protein NS5. We found that sfRNA binds to and stabilises NS5, allowing this protein to inhibit phosphorylation of transcriptional factor STAT1, a key mediator of antiviral signalling.

    This project is aimed to uncover how sfRNA binding effects NS5 conformation and its ability to inhibit STAT1 phosphorylation by identifying interacting sites in both molecules, characterising structural changes in NS5 caused by sfRNA binding and creating mutant viruses incapable of sfRNA-NS5 interactions. It will also investigate whether this mechanism is conserved between all flaviviruses.

    The successful candidate will have an opportunity to join one of the leading flavivirus laboratories and work in the dynamic team of internationally recognised experts at the forefront of flavivirus research. He/she will obtain experience in the wide range of classical and modern research techniques such as cryo-electron microscopy, next generation sequencing, generation of mutant viruses, immunofluorescent virus detection, quantitative PCR, Northern blotting, electrophoretic mobility shift assay, etc. He/she will have an opportunity to communicate their research at the national and international conferences and publish in the leading academic journals.

  • This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

    SARS-CoV-2 is the cause of current COVID-19 pandemic which has already infected >270 million people and killed >5 million of them. Currently deployed and future vaccines are likely to significantly decrease the burden of pandemic, however, new viral variants are emerging that are less susceptible to vaccine-induced immunity. Hence, deeper understanding of what drives viral evolution under the pressure of vaccine-induced immune responses is needed to predict and prepare for the emergence of future variants and inform development of more effective vaccines. The project will employ deep mutational scanning methodology to identify changes in the viral spike protein responsible for altered susceptibility to vaccine-induced antibodies. The implications of identified changes on the properties of spike protein and susceptibility to vaccine-induced antibodies will be investigated using structural analysis and various functional assays. The findings will be critical for predicting viral changes that are likely to emerge in the landscape of vaccinations and provide invaluable information for pre-emptive development of vaccines that will be able to minimise future emergence of vaccine-resistant variants.

View all Available Projects

Publications

Book Chapter

  • Roby, Justin A., Funk, Anneke and Khromykh, Alexander A. (2012). Flavivirus replication and assembly. Molecular virology and control of flaviviruses. (pp. 21-49) edited by Pei-Yong Shi. Norfolk, United Kingdom: Caister Academic Press.

  • Roby, Justin A., Hall, Roy A. and Khromykh, Alexander A. (2011). Nucleic acid-based infectious and pseudoinfectious flavivirus vaccines. Replicating vaccines : A new generation. (pp. 299-320) edited by Philip R. Dormitzer, Christian W. Mandl and Rino Rappuoli. Basel, Switzerland: Springer. doi: 10.1007/978-3-0346-0277-8_13

  • Khromykh, Alexander A., Chang, David C. and Hall, Roy A. (2009). Vaccine development against West Nile Virus. West Nile Encephalitis Virus Infection: Viral Pathogenesis and the Host Immune Response. (pp. 427-451) edited by Diamond, Michael S.. New York: Springer Science + Business Media.

  • Westaway, E. G., Mackenzie, J. M. and Khromykh, A. A. (2003). Kunjin RNA replication and applications of Kunjin replicons. The Flaviviruses: Structure, replication and evolution. (pp. 100-140) edited by Thomas J. Chambers, Thomas P. Monath, Karl Maramorosch, Aaron J. Shatkin and Frederick A. Murphy. San Diego: Academic Press Inc. doi: 10.1016/S0065-3527(03)59004-2

  • Westaway, E. G., Mackenzie, J. M. and Khromykh, A. A. (2002). Replication and gene function in Kunjin virus. Japanese Encephalitis and West Nile Viruses. (pp. 323-352) edited by J. S. Mackenzie, A. D. T. Barrett and V. Deubel. Berlin: Springer.

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

    Flaviviruses are important human pathogens that include West Nile, Dengue, Zika, Yellow fever virus and other viruses. They have a unique ability to produce viral noncoding RNA from their 3' untranslated region by hijacking host exoribonuclease. This RNA, termed subgenomic flaviviral RNA (sfRNA), accumulates in infected cells in high abundance and facilitates viral pathogenesis by supressing antiviral response. However, the molecular mechanism that determines this activity is not fully elucidated. Recently we have discovered that sfRNA of Zika virus executes this function in cooperation with the viral protein NS5. We found that sfRNA binds to and stabilises NS5, allowing this protein to inhibit phosphorylation of transcriptional factor STAT1, a key mediator of antiviral signalling.

    This project is aimed to uncover how sfRNA binding effects NS5 conformation and its ability to inhibit STAT1 phosphorylation by identifying interacting sites in both molecules, characterising structural changes in NS5 caused by sfRNA binding and creating mutant viruses incapable of sfRNA-NS5 interactions. It will also investigate whether this mechanism is conserved between all flaviviruses.

    The successful candidate will have an opportunity to join one of the leading flavivirus laboratories and work in the dynamic team of internationally recognised experts at the forefront of flavivirus research. He/she will obtain experience in the wide range of classical and modern research techniques such as cryo-electron microscopy, next generation sequencing, generation of mutant viruses, immunofluorescent virus detection, quantitative PCR, Northern blotting, electrophoretic mobility shift assay, etc. He/she will have an opportunity to communicate their research at the national and international conferences and publish in the leading academic journals.

  • This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

    SARS-CoV-2 is the cause of current COVID-19 pandemic which has already infected >270 million people and killed >5 million of them. Currently deployed and future vaccines are likely to significantly decrease the burden of pandemic, however, new viral variants are emerging that are less susceptible to vaccine-induced immunity. Hence, deeper understanding of what drives viral evolution under the pressure of vaccine-induced immune responses is needed to predict and prepare for the emergence of future variants and inform development of more effective vaccines. The project will employ deep mutational scanning methodology to identify changes in the viral spike protein responsible for altered susceptibility to vaccine-induced antibodies. The implications of identified changes on the properties of spike protein and susceptibility to vaccine-induced antibodies will be investigated using structural analysis and various functional assays. The findings will be critical for predicting viral changes that are likely to emerge in the landscape of vaccinations and provide invaluable information for pre-emptive development of vaccines that will be able to minimise future emergence of vaccine-resistant variants.