Professor Matt Sweet

Principle Research Fellow

Institute for Molecular Bioscience

Affiliate Associate Professor

School of Chemistry and Molecular Biosciences
Faculty of Science
m.sweet@imb.uq.edu.au
+61 7 334 62082

Overview

Matt Sweet is an NHMRC Senior Research Fellow, the Director of the Centre for Inflammation and Disease Research and Deputy Head of the Division of Cell Biology and Molecular Medicine at the Institute for Molecular Bioscience (IMB) at The University of Queensland, Brisbane, Australia. He studies innate immunity, the body’s danger sensing system that responds to infection, injury and dysregulated homeostasis, and the role of this system in health and disease. Matt’s research team is focused on characterizing the roles of specific innate immune pattern recognition receptors and their downstream signalling pathways/gene products in inflammatory disease processes, as well as in host responses to bacterial pathogens. He has authored ~130 journal articles and book chapters, including in Science, Nature Genetics, Nature Communications (2), Journal of Experimental Medicine (2) and Proceedings of the National Academy of Sciences USA (2), and his career publications have accrued ~8,700 citations.

Biography

I was awarded a PhD (The University of Queensland) in 1996 for my research under the supervision of Prof David Hume into gene regulation in macrophages, immune cells with important roles in health and disease. I subsequently undertook a short postdoctoral position in the same laboratory, focusing on the activation of macrophages by pathogen products. I then embarked on a CJ Martin post-doctoral training fellowship with Prof Eddy Liew, FRS at the University of Glasgow in Scotland. Returning to The University of Queensland, I had a prominent role within the Cooperative Research Centre for Chronic Inflammatory Diseases (including as UQ node head from 2007-2008) and was appointed as a Group Leader at the IMB in 2007. I was subsequently awarded an ARC Future Fellowship, and I have been an NHMRC Senior Research Fellow since 2011.

Key discoveries

  • CpG-containing DNA as an activator of innate immunity, and characterization of the receptor (TLR9) detecting this microbial component.
  • The IL-1 receptor family member ST2 as a critical regulator of innate immunity and inflammation.
  • Inflammatory and antimicrobial functions of histone deacetylase enzymes (HDACs) in macrophages.
  • Effects of the growth factor CSF-1 on inflammatory responses in macrophages.
  • Mechanisms responsible for divergence in TLR responses between human and mouse macrophages, as well as the functional consequences of such divergence.
  • Host evasion strategies used by the bacterial pathogens Salmonella enterica serovar Typhimurium and uropathogenic E. coli.

Research training

I have supervised or co-supervised 19 completed PhD students and 18 completed honours students, as well as 9 post-doctoral researchers. Many of my former staff and students continue to have active research careers around the world (USA, UK, Europe, Australia), including as independent laboratory heads. I currently supervise 3 PhD students in my laboratory, co-supervise another 3 PhD students in other laboratories, and oversee the research activities of 3 post-doctoral researchers in my group. Current and former staff/students have received numerous fellowships and awards during their research careers (e.g. ARC DECRA, NHMRC CJ Martin fellowship, UQ post-doctoral fellowship, Smart State scholarship). I have also examined 15 PhD theses in the fields of innate immunity, inflammation and host defence.

Professional activities

I am an editorial board member of the Journal of Leukocyte Biology and Immunology and Cell Biology. I have served on NHMRC project grant review panels in 2007, 2008, 2009, 2012 (as panel chair) and 2014, as well as a member of the NHMRC RGMS user reference group committee from 2010-2012. I have acted as national representative for the Australasian Society of Immunology (ASI) Infection and Immunity special interest group from 2012 to the present. At UQ, I served as chair of an animal ethics committee from 2013-2014, and co-organized the UQ Host-Pathogen interaction network from 2007-2010 (prior to the establishment of the Australian Infectious Diseases Research Centre).

I have made extensive contributions to conference organization in my discipline. I co-organized the national TLROZ2009 and TLROZ2012 conferences, I organized the first ever Australasian Society for Immunology Infection and Immunity workshop (2009), and I co-organize the annual IMB Inflammation Symposium (2014 to the present). In addition, I have been a member of the organizing committee for ASI2009, the 2014 International Cytokine and Interferon Society conference, the Lorne Infection and Immunity conference (2014 to the present), and the Brisbane Immunology Group annual meeting (2008 to the present). I am currently acting as co-chair for the 2019 World Conference of Inflammation (to be held in Sydney), and chair of the program sub-committee for ASI2017 (to be held in Brisbane).

Research Interests

  • MACROPHAGE INFLAMMATORY PATHWAYS
    Cells of the innate immune system such as macrophages play essential roles in detecting and responding to danger, which can be sensed as a result of infection, injury and/or dysregulated homeostasis. These cells use several families of pattern recognition receptors (PRRs), such as the toll-like receptors (TLRs) and nod-like receptors (NLRs), to recognize specific danger signals. Inappropriate or prolonged PRR activation drives dysregulated inflammation, which is central to the pathology of many acute and chronic diseases. Current research is focused on developing approaches to target PRR signaling pathways and other innate immune pathways for potential applications in inflammatory diseases such as chronic liver disease, sepsis and inflammatory bowel diseases. Areas of specific interest including characterizing mechanisms by which novel TLR complex components provide specificity to inflammatory cytokine production, control of inflammatory outputs by TLR/G protein-coupled receptor cross-talk and the roles of individual HDAC enzymes in macrophage inflammatory pathways.
  • MACROPHAGE ANTIMICROBIAL PATHWAYS
    Innate immunity plays a pivotal role in protecting against invading microorganisms, but successful pathogens are able to overcome this system to cause disease. Indeed, many important pathogens actively target macrophages, residing in these cells or destroying them to avoid immune defence. We study TLR-inducible macrophage antimicrobial responses, and how the Gram-negative bacterial pathogens Salmonella enterica serovar Typhimurium (S. Typhimurium) and uropathogenic E. coli (UPEC) are able to overcome such responses. Our focus is on developing novel anti-infective approaches, through the manipulation of innate immune antimicrobial pathways. Areas of specific interest include understanding how trafficking of zinc and other metal ions contribute to TLR-inducible macrophage antimicrobial responses against S. Typhimurium and UPEC, defining mechanisms by which specific HDAC enzymes control macrophage host defence pathways, and the contributions of UPEC-triggered macrophage cell death to immune defence versus host subversion.
  • SPECIES DIFFERENCES IN INNATE IMMUNITY
    Whilst conservation of a gene or pathway across species is an obvious indicator of its importance, the fact that a gene or a pathway is not conserved does not mean that it isn’t important for one particular species. In fact, in the context of co-evolution of host and pathogen, species-specific responses are likely to be critical for host defence. We have characterized differences in TLR responses between human and mouse, and the mechanisms responsible. Our current focus is on characterizing the roles of individual TLR target genes that are differentially regulated between human and mouse in host defence against bacterial pathogens and in inflammatory responses.

Research Impacts

Every organism and every cell employs some form of innate defence for protection against agents with the ability to cause harm. In complex multicellular organisms, these innate defence systems also have the capacity to cause damage to the organism itself. As such, innate immunity lies at the heart of almost all disease processes. Our fundamental research in this field has the potential to lead to new anti-infective and/or anti-inflammatory agents that may have applications in the health, livestock and/or veterinary sectors.

Specific indicators of impact

  • ~130 career publications, which have collectively accrued ~8,700 citations (average cites/article: >65; most cited article: ~800 citations; >150 citations of my research in Cell, Science, Nature and Nature specialty journals (e.g. Nature Immunology etc)). My publications include ~30 invited review articles, editorials and book chapters, and of these, 4 reviews have received more than 200 citations, another 2 have received more than 100 citations, and 1 received the Dolph Adams award from the Journal of Leukocyte Biology. I have also been invited to guest edit review series for Seminars in Cell and Developmental Biology, Immunology and Cell Biology and Journal of Leukocyte Biology.
  • Contribution to the development and/or validation of several novel small molecule inhibitors of inflammation-relevant proteins, and numerous interactions with the Pharmaceutical/Biotechnology industry.
  • ~75 invitations to speak nationally and internationally at conferences, institute/departmental seminars, and other forums. I have also chaired ~30 sessions at national and international conferences.

Qualifications

  • PhD, The University of Queensland
  • BSc(Hons), The University of Queensland

Publications

View all Publications

Supervision

View all Supervision

Available Projects

  • We have found that specific HDAC enzymes constrain human macrophage antimicrobial responses, particularly the production of mitochondrial reactive oxygen species. Hence, targeting of such enzymes can boost macrophage-mediated clearance of intracellular bacterial pathogens. This project will explore the specific molecular mechanisms by which HDACs constrain macrophage antimicrobial pathways, and will investigate novel anti-infective approaches that target HDAC enzymes.

  • Several projects are available to investigate different aspects of TLR-inducible inflammatory pathways in macrophages, including the role of a novel TLR adaptor in providing specificity to inflammatory cytokine output from macrophages, links between HDACs and metabolic pathways in macrophage-mediated inflammation, the functions of specific GPCRs in regulating TLR-inducible inflammatory pathways in macrophages, and the role of a human-specific TLR-inducible ubiquitin ligase in regulating macrophage inflammatory responses.

View all Available Projects

Publications

Featured Publications

Book Chapter

Journal Article

Conference Publication

  • Stocks, C. J., Kapetanovic, R., Bokil, N., Phan, M. -D, Lo, A., Schembri, M. and Sweet, M. J. (2016). The role of zinc in macrophage antimicrobial responses. In: International Congress of Immunology (ICI), Melbourne, VIC, Australia, (432-432). 21-26 August 2016. doi:10.1002/eji.201670200

  • Sweet, M. J., Schroder, K., Irvine, K. M., Taylor, M., Bokil, N. J., Broomfield, S., Schembri, M. A., Stacey, K. J. and Hume, D. A. (2012). Functional significance of evolutionary divergence in Toll-like receptor-regulated gene expression in human versus mouse. In: Abstracts of the European Congress of Immunology. European Congress of Immunology, Glasgow, Scotland, (297-297). 5-8 September 2012. doi:10.1111/imm.12002

  • Irvine, Katharine M., Andrews, Melanie R., Fernandez, Manuel A., Parton, Robert G., Burns, Christopher J., Su, Stephen, Wilks, Andrew F., Hume, David A. and Sweet, M. J. (2008). The identification of novel CSF-1 target genes in human macrophages. In: Cytokine. 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and-Cytoklin-Research, Montreal Canada, (245-245). Oct 12-16, 2008. doi:10.1016/j.cyto.2008.07.078

  • Van Zuiiien, Wim, Schroder, K, Garceau, V, Sweet, MJ, Kellie, S and Hume, DA (2008). Expression and function of Schlafen-4 in macrophage biology and inflammation. In: Cytokine. 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and-Cytoklin-Research, Montreal Canada, (246-246). Oct 12-16, 2008. doi:10.1016/j.cyto.2008.07.081

  • Irvine, Katharine M., Burns, Christopher J., Wilks, Andrew F., Bu, Xiangyong, Harte, Michael F., Su, Stephen, Hume, David A. and Sweet, Matthew J. (2005). A potent CSF-1 Receptor tyrosine kinase inhibitor targets survival and effector functions in marine macrophage populations. In: Inflammation Research. , , (S148-S148). .

  • Schroder, Kate, Irvine, Katharine M., Biron, Kristian, Lichtinger, Monika, Ravasi, Timothy, Rehli, Michael, Sweet, Matthen J. and Hume, David A. (2005). PU.1 and ICSBP regulate the tlr9 promoter in mouse macrophages. In: Inflammation Research. , , (S186-S187). .

  • Lattin, Jane E., Blomberg, Lovisa M., Daly, Norelle L., Craik, David J., Robinson, Jodie A., Kellie, Stuart, Hume, David A. and Sweet, Matthew J. (2005). Beta-arrestin expression and function in macrophages. In: Inflammation 2005: Book of Abstracts. 7th World Congress on Inflammation: Inflammation 2005: Inflammation, the Key to much pathology, Melbourne, Australia, (S157-S158). 20 - 24 August 2005.

  • Sester, D. P., Beasley, S. J., Sweet, M. J., Stacey, K. J. and Hume, D. A. (1999). CpG DNA effects macrophage CSF-1 receptor cell surface expression, proliferation and survival. In: Innate Resistant to Infection, Society for Leukocyte Biology. 15th International Congress for Society for Leukocyte Biology, Churchill College, Cambridge UK, (). 22-26 September, 1999.

  • Sester, D. P., Sweet, M. J., Stacey, K. J. and Hume, D. A. (1999). Immunostimulatory DNA promotes factor independent survival of macrophages. In: Combined Conference Abstracts: 43rd Annual ASBMB, 18th Annual ANZSCDB and 39th Annual ASPP. ComBio 99, Conrad Jupiters, Gold Coast, (Sym-45-04). 27-30 September, 1999.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

  • Doctor Philosophy — Associate Advisor

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • We have found that specific HDAC enzymes constrain human macrophage antimicrobial responses, particularly the production of mitochondrial reactive oxygen species. Hence, targeting of such enzymes can boost macrophage-mediated clearance of intracellular bacterial pathogens. This project will explore the specific molecular mechanisms by which HDACs constrain macrophage antimicrobial pathways, and will investigate novel anti-infective approaches that target HDAC enzymes.

  • Several projects are available to investigate different aspects of TLR-inducible inflammatory pathways in macrophages, including the role of a novel TLR adaptor in providing specificity to inflammatory cytokine output from macrophages, links between HDACs and metabolic pathways in macrophage-mediated inflammation, the functions of specific GPCRs in regulating TLR-inducible inflammatory pathways in macrophages, and the role of a human-specific TLR-inducible ubiquitin ligase in regulating macrophage inflammatory responses.