Matt Sweet is an NHMRC Leadership Fellow, Group Leader, and Director of Higher Degree Research (DHDR) at the Institute for Molecular Bioscience (IMB) at The University of Queensland, Brisbane, Australia. He was the founding Director of the IMB Centre for Inflammation and Disease Research (2014-2018), also serving as Deputy Head of the IMB Division of Cell Biology and Molecular Medicine during this period. Matt 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 focuses on manipulating the innate immune system for the development of anti-infective and anti-inflammatory strategies. To do so, his lab characterizes 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 >175 journal articles and book chapters, including in Science (2), Science Translational Medicine, Science Immunology, Nature Immunology, Nature Genetics, Nature Communications (4), PNAS USA (6) and Journal of Experimental Medicine (2), and his career publications have accrued >19,000 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 have continued fellowship support since this time, including as an ARC Future Fellow, an NHMRC Senior Research Fellow and an NHMRC Leadership Fellow (current, from 2021).

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.

TLR-inducible zinc toxicity as an antimicrobial weapon of macrophages and the identification of defects in this pathway in cystic fibrosis.

Host evasion strategies used by the bacterial pathogens Salmonella enterica serovar Typhimurium and uropathogenic E. coli.

SCIMP as a novel TLR adaptor that mediates TLR tyrosine phosphorylation and selective cytokine outputs.

Genes and pathways associated with the severity of chronic liver disease.

Molecular mechanisms controlling macrophage immunometabolism, as well as associated inflammatory and antimicrobial responses.

Anti-inflammatory and antibacterial activities of the metabolite ribulose-5-phosphate.

Research training

I have supervised or co-supervised 29 completed PhD students and 22 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 5 PhD students in my laboratory, co-supervise 4 PhD students in other laboratories, and oversee the research activities of 2 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 >25 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 Seminars in Cell & Developmental Biology, and have served as an editorial board member for several other journals in the past e.g. Immunology and Cell Biology. I have served on NHMRC project grant review panels in 2007, 2008, 2009, 2012 (as panel chair) and 2014, NHMRC Ideas panels in 2020 and 2024, NHMRC Investigator panels in 2021 and 2022, as well as a member of the NHMRC RGMS user reference group committee from 2010-2012. I acted as national representative for the Australasian Society of Immunology (ASI) Infection and Immunity special interest group from 2012-2017. 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 am currently Director of Higher Degree by Research at IMB, overseeing HDR student recruitment and training.

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 (ASI) Infection and Immunity workshop (2009), was chair of the ASI Program Committee and co-organizer of the Infection and Immunity workshop for ASI2017, and I co-organized the annual IMB Inflammation Symposium (2014-2018). I also co-chaired the 2019 World Conference of Inflammation (Sydney, September 2019). 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 (2014-2020), and the Brisbane Immunology Group annual meeting (2008 to the present).

I am an NHMRC Leadership Fellow with joint apointments at the Institute for Molecular Bioscience (IMB) and School of Pharmacy, UQ. My research interests lie in the fields of peripheral pain mechanisms, target identification and analgesic drug discovery. I investigate the contribution of ion channels to sensory neuronal physiology using highly subtype-selective toxins isolated from venomous animals with the aim to develop novel analgesics with improved efficacy and tolerability.