Uncovering and characterising new alphavirus and flavivirus host co-factors

Suitable for Honours or PhD Students.

BACKGROUND

The global range of mosquito-borne diseases is already expanding, with climate change likely to exacerbate this trend.  Over 10 million cases of chikungunya virus (CHIKV) infection have been recorded globally, and often manifests as debilitating polyarthralgia/polyarthritis (pain/inflammation in multiple joints) that can last months or years.  The only available treatment targets pain and inflammation and there are no specific anti-viral treatments or vaccines approved for human use. CHIKV belongs to a group of globally distributed arthritogenic alphaviruses that include the Mayaro virus (MAYV), Getah virus (GETV), and Ross River virus (RRV) which records ~4600 annual cases in Australia.

AIM

The project will focus on identifying new human co-factors for CHIKV replication, by exploiting a recent finding of a cell line where CHIKV replication fails.  High-throughput technologies such as CRISPR/Cas9 and Whole Human Genome Lentivirus Open Reading Frame Pools will be exploited to identify new crucial CHIKV host factors. Follow up investigations including knockout mice, chimeric/mutant viruses, structure determination (i.e., cryo-EM, crystallography), antiviral screening etc. would be envisaged to fully characterize new virus-host interactions. A similar approach could be taken for Japanese Encephalitis Virus (JEV), the virus recently causing outbreaks in Australia. 

METHOD

The project will involve molecular biology, virological assays, and animal handling, and will be supported by a team of virologists and bioinformaticians.  QIMR Berghofer requires and arranges that all staff working in the physical containment 3 (PC3) facility on JEV are vaccinated.