Cooperation between sfRNA and non-structural protein NS5 for flavivirus immune evasion

Project opportunity

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.

Scholarship value

As a scholarship recipient, you'll receive: 

  • living stipend of $28,854 per annum tax free (2022 rate), indexed annually
  • tuition fees covered
  • single Overseas Student Health Cover (OSHC)

Supervisor

Professor Alexander Khromykh

School of Chemistry and Molecular Biosciences

Email: alexander.khromykh@uq.edu.au

Preferred educational background

Your application will be assessed on a competitive basis.

We take into account your

  • previous academic record
  • publication record
  • honours and awards
  • employment history.

A working knowledge of structural biology, particularly cryo-electron microscopy, would be of benefit to someone working on this project.

The applicant will demonstrate academic achievement in the field(s) of virology, microbiology, immunology, molecular biology or biochemistry and the potential for scholastic success.

A background or knowledge of general molecular biology techniques (cell culture, PCR, cloning, protein expression and purification, isolation of DNA and RNA, Western blotting, etc..) is highly desirable.

Latest commencement date

If you are the successful candidate, you must commence by Research Quarter 1, 2023. You should apply at least 3 months prior to the research quarter commencement date.

If you are an international applicant, you may need to apply much earlier for visa requirements.

How to apply

You apply for this project as part of your PhD program application.

View application process