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.
- Immunity to virus infection and in particular CD8+ T cells;
- Poxviruses and herpesviruses;
- Antigen presentation.
- NHMRC Project Grant, APP1049760; $517,097; CIA: MC Cook, CIB: DC Tscharke. Title: Genomic medicine for human immune deficiency. 2013-2015.
- ARC Future Fellowship, FT110100310; $714,528; Fellow DC Tscharke. Title: Virus and host genes and the outcome of infection. 2012-2015.
- NHMRC Project Grant, APP1023141; $562,350; CIA: DC Tscharke, CIB: A Purcell (Melb). Title: Quantification of antigen presentation to CD8 T cells during virus infection. 2012-2014.
- NHMRC Project Grant, no APP1005846, $555,048. CIA: F. Carbone, CIB: D. Tscharke. Title: Anti-viral immunity and the survival of cells infected with herpes simplex virus in vivo. 2011-2013.
- NHMRC Project Grant, no 509199, $483,750. CIA: F. Carbone, CIB: D. Tscharke. Title: Why eczema increases the severity of virus infections. 2008-2010.
- Subcontract to National Institutes of Health, USA grant HHSN272200700038C, Subaward PI: C. Goodnow, D. Tscharke share: USD$291,500. Title: Systems approach to immunity and inflammation. 2008-2012.
- NHMRC R Douglas Wright Biomedical Career Development Award, no 418108, D. Tscharke, Fellow. Title: CD8+ T cell immunity to viruses and recombinant vaccines. 2007-2011.
- National Institutes of Health, USA grant RO1AI067401, USD$754,850. D. Tscharke PI (or CIA), G. Karupiah and M. Buller. Title: CD8+ T cell specificity in mouse models of smallpox vaccination and challenge. Sept 2006 - Aug 2010.
- Complete list available through ISI Researcher ID
- 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.
- Wong YC, Smith SA, and Tscharke DC. (2013). Systemic toll-like receptor ligation and selective killing of dendritic cell subsets fail to dissect priming pathways for anti-vaccinia virus CD8+ T cells. J Virol 87: 11978-86.
- Lin LCW, Flesch IEA, and Tscharke DC. (2013). Immunodomination during peripheral vaccinia virus infection. PLoS Pathog. 9(4): e1003329.
- 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.
- Yuen TJ, Flesch IEA, Hollett NA, Dobson BM, Russell TA, Fahrer AM and Tscharke DC (2010) Analysis of A47, an immunoprevalent protein of vaccinia virus leads to a re-evaluation of the total anti-viral CD8+ T cell response. J Virol 84:10220-9.
- Flesch IE, Woo Y-P, Wang Y, Panchanathan V, Wong Y-C, La Gruta NL, Cukalac T and Tscharke DC (2010). Altered CD8+ T cell immunodominance after vaccinia virus infection and the naïve repertoire in inbred and F1 mice. J. Immunol. 184: 45-55.
- Assarsson E, Greenbaum JA, Sundstrom M, Schafer L, Hammond JA, Pasquetto V, Oseroff C, Hendrickson RC, Lefkowitz EJ, Tscharke DC, Sidney J, Grey HM, Head SR, Peters B, and Sette A. (2008). Kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes. PNAS 105:2140-5.
- 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