PROJECTS IN VIROLOGY COMMENCING 2021
Virology Research, NSW Health Pathology East and UNSW Research Laboratories, Prince of Wales Hospital
Ph: +61-2-93829188 Fax: +61-2-93984275
Prof William Rawlinson, T: 93829113, w.rawlinson@unsw.edu.au
Senior Virologist and Director of Serology and Virology Division (SAViD), SEALS Microbiology
Molecular biology of viruses: Projects in the Virology Research Laboratory are available in basic and applied molecular and cellular virology, funded by the NHMRC, ARC, and charitable grants. They involve training in molecular methods, protein chemistry, statistics and genomic analysis.
Honours projects are internationally competitive and align with the student’s research interests. The projects provide a solid foundation for extension into a research project for those seeking to undertake a PhD. We encourage you to visit the laboratory to meet with us, and discuss potential projects in more detail.
Program 1: CMV pathogenesis, placental infection and adverse pregnancy outcomes
Project leader: Prof William Rawlinson, T: 93829113, w.rawlinson@unsw.edu.au
Places available: 1-2
During pregnancy, human cytomegalovirus (CMV) can infect the placenta, and the developing fetus, resulting in congenital CMV illness. There are ~2000 Australian infants born each year with congenital CMV infection, and ~10% develop symptoms including sensorineural hearing loss and mental disability. Understanding pathogenesis of CMV infection is critical for developing more effective treatments for congenital CMV. These studies investigate pathways of CMV-induced placental damage, transplacental transmission, and factors influencing disease outcome. We have discovered CMV modulates signaling pathways involved in placental development and are now further characterizing these changes in experimental models of human primary placental cells, which allow experiments that are not possible in pregnant women. Ultimately this work aims to prevent congenital CMV.
Selected articles:
- Van Zuylen WJ, Ford CE, Wong DDY, Rawlinson WD (2016) Human CMV Modulates Expression of Noncanonical Wnt Receptor ROR2 To Alter Trophoblast Migration. Journal of Virology 90(2): 1108-1115
- Zheng QU, Huynh K, van Zuylen W, Craig ME, Rawlinson WD (2018) Cytomegalovirus Infection in Day Care Centres: A Systematic Review and Meta-analysis of Prevalence of Infection in Children. Reviews of Medical Virology 29:e2011
- Huynh K, van Zuylen W, Ford C, Rawlinson WD (2018) Selective modulation of Wnt-binding receptor tyrosine kinase ROR2 expression by human cytomegalovirus regulates trophoblast migrationournal Journal of General Virology 1-6 DOI 10.1099/jgv.0.001179
Program 2: Novel antiviral strategies to treat human cytomegalovirus infection
Project leader: Dr Stuart Hamilton T: 93829096, Stuart.Hamilton@health.nsw.gov.au
Places available: 1-2
Despite the enormous clinical and social importance of congenital CMV, there are currently no licensed therapeutics available for the treatment of CMV infection during pregnancy. This is due to limited evidence for antiviral efficacy and associated drug toxicity to the developing fetus. We have established an ex vivo human placental model system to simulate placental development and function during pregnancy. In collaboration with international partners, this project is investigating the safety and efficacy profiles of novel CMV antiviral compounds in cell culture and placental explant models. These studies will guide future directions in therapeutic development in both congenital CMV and transplantation settings.
Selected articles:
- Hahn F, Hutterer C, Henry C, Hamilton S, Strojan H, Kraut A, Schulte U, Schütz M, Kohrt S, Wangen C, Pfizer J, Couté Y, Rawlinson W, Strobl S, Marschall M (2018) Human CMV; antiviral compounds; experimental drug development; drug immobilization by linker coupling; mass spectrometry-based target identification; biological properties and mode of action. Antiviral Research 159:84-94 01 Nov 2018
- Hamilton ST, Hutterer CH, Egilmezer E, Milbradt J, Marschall M, Rawlinson WD (2018) Human cytomegalovirus utilises cellular dual-specificity tyrosine phosphorylation-regulated kinases during placental replication. Placenta 72-73:10-19 01 Dec 2018
- Sonntag E, Hamilton ST, Bahsi H, Wagner S, Jonjic S, Rawlinson WD, Marschall M, Milbradt J (2016) Cytomegalovirus pUL50 is the multi-interacting determinant of the core nuclear egress complex (NEC) that recruits cellular accessory NEC components. Journal General Virology 97:1676-1685
Program 3: Virome and type 1 diabetes
Project leaders: Prof Maria Craig T: 9113 3637, m.craig@unsw.edu.au; Dr Ki Wook Kim T: 9382 9096 k.w.kim@unsw.edu.au
Places available: 1
Type 1 diabetes (T1D) is increasing in childhood and we do not know why. The rise has occurred rapidly, particularly among children without a family history. This strongly supports the major contribution of environmental factors in T1D aetiology. Viruses have been identified as prime environmental triggers due to their strong molecular and epidemiological associations with T1D. Extensive research by us and others have clearly demonstrated the involvement of enteroviruses in the pathogenesis of T1D. In stark contrast, very few studies have examined the relationship of other virus infections to T1D. Using cutting-edge Next Generation Sequencing techniques, this study will investigate the gut and respiratory “virome” (entire population of viruses) in children who are at risk of developing T1D, participating in the nation-wide ENDIA cohort study (www.endia.org.au). Furthermore, the virome of pancreatic donor tissues collected by the Network for Pancreatic Donors with Diabetes (nPOD; https://www.jdrfnpod.org) will be investigated. Data resulting from this work is anticipated to facilitate future development of vaccines to prevent viral causes of T1D.
Selected articles:
- Kim KW, Allen DW…Rawlinson WD, Craig ME (2020) Higher frequency of vertebrate-infecting viruses in the gut of infants born to mothers with type 1 diabetes. Pediatric diabetes, 21:271-279
- Kim KW, Allen DW…Rawlinson WD, Craig ME (2019) Distinct Gut Virome Profile of Pregnant Women With Type 1 Diabetes in the ENDIA Study. Open forum infectious diseases, 6:ofz025
- Kim KW, Horton JL, Pang ICN, Jain K, Leung C, Isaacs SR, Bull RA, Luciani F, Wilkins MR, Catteau J, Lipkin WI, Rawlinson WD, Briese T, Craig ME (2019) Higher abundance of enterovirus A species in the gut of children with islet autoimmunity. Scientific Reports, 9(1):1749
- Allen DW, Kim KW, Rawlinson WD, Craig ME (2018) Maternal virus infections in pregnancy and type 1 diabetes in their offspring: systematic review and meta-analysis of observational studies. Reviews in Medical Virology, 22:e1974. doi: 10.1002/rmv
Program 4: Molecular mechanisms for enterovirus induced ?-cell lysis
Project leaders: Prof Maria Craig T: 9113 3637, m.craig@unsw.edu.au; Dr Ki Wook Kim T: 9382 9096 k.w.kim@unsw.edu.au
Places available: 1
Enterovirus (EV) infection is a major environmental factor in the aetiology of T1D. Little is known about the mechanisms by which these viruses induce apoptosis and/or functionally impair pancreatic ?-cells. Previously, we have shown that EV infection induces cytokine and chemokine production by ?-cells and alters the abundance of microRNAs that are important for immune response to viral infection and cell signaling pathways. Currently, we are using Next Generation Sequencing and EV-infected human pancreatic islets to investigate the intra-host evolution of EVs during infection and how it may contribute to the establishment of viral persistence – a candidate mechanism via which EVs may induce prolonged ?-cell dysfunction and autoimmunity. This project will apply a wide range of molecular and cell culture techniques.
Selected articles:
- Isaacs SR, Kim KW, Cheng JX, Bull RA, Stelzer-Braid S, Luciani F, Rawlinson WD, Craig ME (2018) Amplification and next generation sequencing of near full-length human enteroviruses for identification and characterisation from clinical samples. Scientific Reports, 8:11889
- Kim KW, Ho A, Alshabee-Akil A, Hardikar AA, Kay TWH, Rawlinson WD and Craig ME (2016) Coxsackievirus B5 Infection Induces Dysregulation of microRNAs Predicted to Target Known Type 1 Diabetes Risk Genes in Human Pancreatic Islets. Diabetes, 65(4), 996-1003. doi:10.2337/db15-0956
- Thomas H (2016) Diabetes: Enterovirus dysregulates islet miRNAs. Nature Reviews Endocrinology, 12:2-2
Program 5: Respiratory Viruses
Project leader: Dr Sacha Stelzer-Braid, 9382 9096, s.stelzer-braid@unsw.edu.au
Places available: 1
Respiratory viral infections are a common cause of illness and an important cause of morbidity and mortality in the community. The SARS-CoV-2 pandemic has shown that we don’t fully understand how different viruses are transmitted and mutate within the community. We are carrying out studies on SARS-CoV-2 and other common respiratory viruses (incl enterovirus, rhinovirus) to determine phylogenetic relationships of viruses isolated from patients suffering from severe disease.
Selected articles:
- Stelzer-Braid, S., Wynn, M., Chatoor, R., Scotch, M., … Britton, P. N., Newcombe, J., Rawlinson, W. D. (2019) Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations. Journal of Clinical Virology, vol. 122, pp. 104216 – 104216.
- Suresh,S., Rawlinson, W.D., Andrews, P.I., Stelzer-Braid, S (2019) Global epidemiology of non-polio enteroviruses causing severe neurological complications: a systematic review and meta-analysis. Reviews in Medical Virology, vol. 30, pp. e2082, http://dx.doi.org/10.1002/rmv.2082
- Stelzer-Braid S., Liu N., Doumit M., D’Cunha R., Belessis Y., Jaffe A., Rawlinson W.D. (2017) Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data. Journal of Medical Virology, doi: 10.1002/jmv.24794.
Program 6: Transmission risk of HBV from HBcAb positive donors through organ transplantation
Project Leader: Dr Vidiya Ramachandran, 93829135, vidiya.ramachandran@health.nsw.gov.au
Places available: 1
This project will investigate the potential for transmission of hepatitis B virus (HBV) through organs from donors who have HBV positive serological markers, specifically hepatitis B core antibody (HBcAb). The risk appears to differ according to the organ implanted, being very high in the case of the liver and low for the rest of organs. However, the final confirmation of the suitability of using HBcAb positive donors in organ transplants is the absence of viral transmission to recipients. Our studies are of the prevalence of these donors in the Australian population, whether or not sero-conversion and/or positive HBV DNA results have appeared among the recipients, the likelihood of HBV transmission through different organs, and the optimum therapy for these recipients.
Selected articles:
- Martinez M, Kok C, Baleriola C, Robertson P, Rawlinson WD (2015) Investigation of occult hepatitis B virus infection in anti-HBc positive patients from liver clinic. PLoSone 2015. 10(3):e0117275
- Waller K, De La Mata N, Wyburn K, Kelly P, Ramachandran V, Rawlinson W, Webster AC (2018) Incidence, prevalence and residual infection risk of HIV in increased risk groups presenting as potential organ donors in Australia: A systematic review and meta analysis. Transplantation. Lippincott Williams & Wilkins. 102: S356 (1 page). 01 Jul 2018
