The Tscharke Group - Viruses and Immunity
The Tscharke Lab has interests in the pathogenesis and immunology of large DNA virus infections. Our research has three major themes:
1. Understanding herpes simplex virus latency, with a particular interest in viral and host gene expression during the latent phase of infection. Our hypothesis is that herpes simplex latency is more dynamic than previously appreciated and that the virus is under host control during this stage of infection rather than being entirely quiescent.
2. Quantitative studies of the presentation of viral antigens to the immune system (especially CD8+ T cells) during infection. Our interest here is in understanding how the levels of presentation relate to anti-viral immune responses and in turn how this information can be exploited in vaccine development.
3. Uncovering the roles of viral and host genes in viral pathogenesis. This includes studies of genes of vaccinia virus that might be an impediment to use of this virus as a vaccine vector, genes of herpes simplex virus that block antigen presentation and genes involved in effective host responses.
In addition, we are continually improving our research tools and methods. For example, incorporating CRISPR/Cas9 genome engineering methods in our methods in engineer the viruses we need for our investigations. Specific projects within this range are tailored to the interests of students.
Research interests
- Immunity to virus infection and in particular CD8+ T cells;
- Poxviruses and herpesviruses;
- Antigen presentation.
Recent grants
- NHMRC Investigator Grant (L2), GNT2008990, $2,072,570.00, D Tscharke Leadership Fellow. Title: Reducing the burden of DNA viruses on human health. 2022-2026.
- NHMRC Ideas Grant, GNT2003395, $800,085, DC Tscharke CIA, R Natoli CIB, U Schumann CIC. Title: Targeting miRNA biogenesis to treat herpes simplex virus latency. 2021-2023.
- MS Research Australia, Incubator Grant, $25,000, DC Tscharke CI, with co-applicants: G Grau, R Bowden, F Mash-Wakefield, S Hawke. Tracking safety and markers of response to Cladribine treatment. 2020-2021.
- ARC Discovery Project, DP190101325, $560,000, DC Tscharke CIA, SM Man CIB. Title: The cellular basis of sex-specific responses to virus infection. 2019-2022.
- CRC for Developing Northern Australia, CRC-P, $1.152m, Porosus Pty Ltd (Lead participant), Lagoon Crocodile Farm, Croc Pac Pty. Ltd., University of Queensland, LaTrobe University, ANU (DC Tscharke), Berrimah Veterinary Laboratories, James Cook University, Qld Dept of Health, NT Dept of Health. Title: Strategies to prevent two viruses devaluing Australian crocodile skins. 2018-2020.
- NHMRC Project Grant, GNT1126599, $981,000, DC Tscharke CIA, A Abendroth CIS, B Slobedman, CIC. Title: Understanding the role of ongoing viral activity in herpes simplex virus latency. 2017-2020.
- NHMRC Project Grant, GNT1084283, $1,114,125, DC Tscharke CIA, N La Gruta (U. Melb.) CIB, A Purcell (Monash) CIC, N Croft (Monash) CID. Title: Recognition of virus-infected cells by T cells. 2015-2019.
- UK Medical Research Council (MRC) Research Grant, £630.474, GL Smith, B Ferguson (DC Tscharke co-investigator); Understanding how innate immune evasion strategies affect adaptive immunity and the application to vaccine development. 2015-2018.
- NHMRC Project Grant, GNT1084342, $268,538, DC Tscharke (sole CI). Title: A humanised mouse model for herpes simplex virus pathogenesis. 2015-2017.
Selected publications
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Complete list available at Google Scholar
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Lin LCW, Croft SN, Croft NP, Wong YC, Smith SA, Tang S-S, Purcell AW, and Tscharke DC. (2021). Direct priming of CD8+ T cells persists in the face of cowpox virus inhibitors of antigen presentation. J. Virol. 95:e00186-21.
Gowripalan A, Smith S, Stefanovic T, and Tscharke DC. (2020). Rapid poxvirus engineering using CRISPR/Cas9 as a selection tool. Commun. Biol. 3: 643.
Croft S, Wong YC, Smith SA, Flesch IEA, and Tscharke DC. (2020). Surprisingly Effective Priming of CD8+ T cells by Heat-Inactivated Vaccinia Virus Virions. J. Virol.: JVI.01486-20.
Singh N, and Tscharke DC. (2020). Herpes simplex virus latency is noisier the closer we look. J Virol 94: e01701-19.
Fox D, Mathur A, Xue Y, Liu Y, Tan WH, Feng S, Pandey A, Ngo C, Hayward JA, Atmosukarto II, Price JD, Johnson MD, Jessberger N, Robertson AAB, Burgio G, Tscharke DC, Fox EM, Leyton DL, Kaakoush NO, Märtlbauer E, Leppla SH, and Man SM. (2020). Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome. Nat. Commun. 11: 760.
Croft NP, Smith SA, Pickering J, Sidney J, Peters B, Faridi P, Witney MJ, Sebastian P, Flesch IEA, Heading SL, Sette A, La Gruta NL, Purcell AW, and Tscharke DC. (2019). Most viral peptides displayed by class I MHC on infected cells are immunogenic. PNAS: 116: 3112–3117.
Wong YC, Croft S, Smith SA, Lin LCW, Cukalac T, La Gruta NL, Drexler I, and Tscharke DC. (2019). Vaccinia virus strain MVA can induce optimal CD8+ T cell responses to directly primed antigens depending on vaccine design. J. Virol. 93:e01154-19.
Wu T, Guan J, Handel A, Tscharke DC, Sidney J, Sette A, Wakim LM, Sng XYX, Thomas PG, Croft NP, Purcell AW, and La Gruta NL. (2019). Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses. Nat. Commun. 10: 2846.
Park SL, Zaid A, Hor JL, Christo SN, Prier JE, Davies B, Alexandre YO, Gregory JL, Russell TA, Gebhardt T, Carbone FR, Tscharke DC, Heath WR, Mueller SN, and Mackay LK. (2018). Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses. Nature Immunol. 19: 183-91
Russell TA, and Tscharke DC. (2016). Lytic Promoters Express Protein during Herpes Simplex Virus Latency. PLoS Pathog. 12: e1005729.
Tscharke DC, Croft NP, Doherty PC, and La Gruta NL. (2015). Sizing up the key determinants of the CD8+ T cell response. Nat. Rev. Immunol. 15: 705-16.
Ma, J. Z., Russell, T. A., Spelman, T., Carbone, F. R., and Tscharke, D. C. (2014). Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response. PLoS Pathog 10:e1004237.
Mackay, L. K., Rahimpour, A., Ma, J. Z., Collins, N., Stock, A. T., Hafon, M.-L., Vega-Ramos, J., Lauzurica, P., Mueller, S. N., Stefanovic, T., Tscharke, D. C., Heath, W. R., Inouye, M., Carbone, F. R., and Gebhardt, T. (2013). The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin. Nature Immunol 14: 1294-1301.
Croft NP, Smith SA, Wong YC, Tan CT, Dudek NL, Flesch IEA, Lin LCW, *Tscharke DC, and *Purcell AW. (2013). Kinetics of Antigen Expression and Epitope Presentation during Virus Infection. PLoS Pathog. 9: e1003129. *Joint senior authors.
Moutaftsi M, Peters B, Pasquetto V, Tscharke DC, Sidney J, Bui HH, Grey H, and Sette A. (2006). A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virus. Nat. Biotechnol. 24:817-9.
Tscharke DC , Karupiah G, Zhou J, Palmore T, Irvine KR, Haeryfar SMM, Williams S, Sidney J, Sette A, Bennink JR, and Yewdell JW. (2005). Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines. J. Exp. Med. 201:95-104.
Norbury CC, Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, Bennink JR, and Yewdell JW. (2004). CD8 + T Cell Cross-Priming via Transfer of Proteasome Substrates. Science 304:1318-21.
Tscharke DC , and Smith GL. (1999). A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J. Gen. Virol. 80:2751-5.
Simmons A, and Tscharke DC. (1992). Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J. Exp. Med. 175: 1337-44
Research centre
Contacts
Professor David Tscharke
