Professor Si Ming Man

PhD
Group Leader, Department of Immunology and Infectious Disease
College of Health & Medicine
T: +61 612 56793

Areas of expertise

  • Innate Immunity 110707
  • Immunology 1107
  • Microbiology 0605
  • Medical Microbiology 1108
  • Medical Bacteriology 110801
  • Medical Infection Agents (Incl. Prions) 110802
  • Bacteriology 060501
  • Infectious Diseases 110309
  • Infectious Agents 060502
  • Gastroenterology And Hepatology 110307
  • Cancer Cell Biology 111201
  • Tumour Immunology 110709
  • Oncology And Carcinogenesis 1112
  • Medical Biochemistry And Metabolomics 1101

Research interests

Our lab investigates the role of innate immunity in infectious diseases and cancer. Pattern-recognition receptors are germ-line encoded innate immune sensors which detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). These receptors activate signalling pathways and mediate the production of inflammatory cytokines, type I interferons and other anti-microbial molecules. We use cutting-edge technology to study the mechanisms by which host sensors recognise bacteria, viruses and parasites, and how these sensors shape the overall immune response to infection. We investigate the role of disease-fighting immune proteins in destroying multidrug resistant pathogens. We also study the molecular basis by which uncontrolled inflammation can lead to the development of cancer, autoimmunity and inflammatory diseases.

Biography

Si Ming received his BMedSc from UNSW Sydney (Honours Class I and the University Medal) and Ph.D. from the University of Cambridge in 2013 for his work on inflammasomes in the host defence against Salmonella infection. He obtained his postdoctoral training from St. Jude Children’s Research Hospital, USA, where he studied immune signalling pathways in the host response to infection and cancer. Currently, he is a CSL Centenary Fellow at the Australian National University, Australia, where his laboratory focuses on innate immunity in the host defence against infectious diseases and the development of cancer and other chronic diseases.

Si Ming is a Clarivate™ Highly Cited Researcher, recognised for producing, in the last decade, multiple highly-cited papers that rank in the top 1% by citations for field and year in the Web of Science™.

Si Ming was a recipient of the Pfizer-Showell Award (2019) and the Thermo Fisher Trainee Achievement Award (2016) from the American Association of Immunologists, the Milstein Young Investigator Award from the International Cytokine & Interferon Society (2016), the Jim Pittard Early Career Award from the Australian Society for Microbiology (2017), the Royal Society of NSW Edgeworth David Medal (2019), the Eppendorf Edman Early Career Award from the Australian Society for Biochemistry & Molecular Biology (2020), the Australian Society for Medical Research Peter Doherty Leading Light Award (2020), an NHMRC Research Excellence Award for the highest-ranked Early Career Fellowship (2015) and an NHMRC Research Excellence Award for the highest-ranked Career Development Fellowship Biomedical Level 1 (2019). He also received the 2019 Commonwealth Health Minister's Medal for Excellence in Health and Medical Research and the 2021 CSL Centenary Fellowship.

Si Ming gives lectures in the following ANU undergraduate courses: BIOL3144 Advanced and Applied Immunology; BIOL3108 Hallmarks of Cancer.

Researcher's projects

We welcome applications from undergraduate, Honours and PhD students, and research assistants and Postdoctoral fellows. We offer Summer Scholarships and Short Projects (e.g. Advanced Studies Course/ASC, SCNC2101 and SCNC3101, and BIOL3208). E-mail Si Ming (siming.man@anu.edu.au) for further information regarding project details and position availability.

Possible project areas we have available include:

  • Uncovering how host cells recognise and kill human pathogens, including bacteria and viruses.
  • Unravelling the molecular mechanisms of inflammasome formation.
  • Understanding the role of innate immune sensors in regulating the development of cancer and the composition of the gut microbiota.
  • Identifying novel activators and inhibitors of the innate immune system to prevent and treat infection, autoinflammatory diseases and cancer.

Current or past theses of PhD students:

  • Microbial activators of the inflammasome, 2017-2021.
  • Guanylate-binding proteins as mediators of inflammasome activation in response to bacterial infection, 2018-2022.
  • Inflammasomes in tumourigenesis, 2018-2022.
  • The role of cytosolic nucleic acid sensors in colitis and colorectal cancer, 2018-2022.
  • Identification of novel innate immune pathogen-recognition receptors of bacterial pathogen-associated molecular patterns, 2019-2023.

Current or past theses of Honours students:

  • Molecular mechanisms of inflammasome activation by enterotoxins of the foodborne pathogen Bacillus cereus, 2018, Awarded First Class Honours.
  • Transmembrane regions of the pore-forming toxin Haemolysin BL are required for inflammasome activation but not membrane binding, 2019, Awarded First Class Honours and the University Medal.
  • Clostridium perfringens is a novel activator of the NLRP3 inflammasome, 2019, Awarded First Class Honours and the University Medal.
  • The molecular mechanism of inflammasome activation, 2020-2021, Awarded First Class Honours and the University Medal.
Techniques you will learn: Western blots, genetic engineering, cloning, molecular biology and protein techniques, ELISA, electron microscopy, confocal microscopy, liposome technology, mammalian and bacterial cell culture.

 

SELECTED PUBLICATIONS

Man, S.M*., Karki, R*., Sasai, M., Place, D.E., Kesavardhana, S., Temirov, J., Frase, S., Zhu, Q., Malireddi, R.K.S., Kuriakose, T., Peters, J.L., Neale, G., Brown, S.A., Yamamoto, M., Kanneganti, T.D. (2016) IRGB10 liberates bacterial ligands for sensing by the AIM2 and caspase-11–NLRP3 inflammasomes. Cell. 167:382–396. *Co-first author.

  • Featured in Developmental Cell: Previews: Hoss, F. Budden, C. and Latz, E. (2016) IRGB10 exposes bacteria’s intimate secrets. Developmental Cell. 39:7–8.
  • Recommended by Faculty of 1000 (F1000).

 Man, S.M*., Zhu, Q*., Zhu, L*., Liu, Z*., Karki, R., Malik, A., Sharma, D., Li, L., Malireddi, R.K.S., Gurung, P., Neale, G., Olsen, S.R., Carter, R.A., McGoldrick, D.J., Wu, G., Finkelstein, D., Vogel, P., Gilbertson, R.J., Kanneganti, T.D. (2015) Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell. 162:45-58. *Co-first author.

  • Featured in Cell: Previews: Rommereim, L.M., Subramanian, N. (2015) AIMing 2 curtail cancer. Cell. 162:18-20.
  • Featured in Science Signaling: Editor’s Choice – Our AIM is 2 prevent cancer (2015) Science Signaling. 8:EC234.
  • Featured in Cancer Discovery: Research Watch: AIM2 inhibits intestinal stem cell proliferation in colorectal cancer (2015) Cancer Discovery. 5(8)

 Karki, R*., Man, S.M*., Malireddi, R.K.S., Kesavardhana, S., Zhu, Q., Burton, A.R., Sharma, B.R., Pelletier, S., Vogel, P., Rosenstiel, P., Kanneganti, T.D. (2016) NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer. Nature. 540:583–587. *Co-first author.

  • Featured in Nature Reviews Immunology: Research Highlights: Leavy, O. (2017) Tumour immunology: NLRC3 inhibits mTOR in colorectal cancer. Nature Reviews Immunology. doi: 10.1038/nri.2016.152.
  • Featured in Nature Reviews Gastroenterology & Hepatology: News & Views: Gao, T., Evers, B.M. (2017) A new innate immune sensor – functions from inside the colonic epithelium. Nature Reviews Gastroenterology & Hepatology. doi:10.1038/nrgastro.2017.10
  • Featured in Science Signaling: Papers of note in Nature: Gough, N.R. (2017) NLRC3 blocks PI3K signaling. Science Signaling. 10(460).
  • Featured in Cancer Discovery: Research Watch: The Cytoplasmic Sensor NLRC3 Inhibits mTOR Signaling in Tumors. (2017) Cancer Discovery DOI: 10.1158/2159-8290.CD-RW2017-001.

Man, S.M., Karki, R., Malireddi, R.K.S., Neale, G., Vogel, P., Yamamoto, M., Lamkanfi, M., Kanneganti, T.D. (2015) The transcription factor IRF1 and guanylate-binding proteins target AIM2 inflammasome activation by Francisella infection. Nature Immunology. 16:467–475.

  • Featured in Nature Immunology: News & Views: Fitzgerald, K.A. Rathinam, V.A.K. (2015) GBPs take AIM at Francisella. Nature Immunology. 16:443–444.

Mathur, A., Feng, S., Hayward, J.A., Ngo, C., Fox, D., Atmosukarto, I.I., Price, J.D., Schauer, K., Märtlbauer E., Robertson, A.A.B., Burgio, G., Fox, E.M., Leppla, S.H., Kaakoush, N.O., Man, S.M.  (2019) A multi-component toxin from Bacillus cereus incites inflammation and shapes host outcome via the NLRP3 inflammasome. Nature Microbiology. 4:362–374. Senior author.

  • Covered by Channel Nine 6pm News, ABC News, ABC Radio and Online media.
  • Altmetric Score: 135.

Fox, D*., Mathur, A*., Xue, Y., Liu, Y., Tan, W.H., Feng, S., Pandey, A., Ngo, C., Hayward, J.A., Atmosukarto, I.I., Price, J.D., Johnson, M.D., Jessberger, N., Robertson, A.A.B., Burgio, G., Tscharke, D.C., Fox, E.M., Leyton, D.L., Kaakoush, N.O., Märtlbauer E., Leppla, S.H., Man, S.M.  (2020) Bacillus cereus non-Haemolytic enteroxin activates the NLRP3 inflammasome. Nature Communications. 11:760. *Co-first author. Senior author.

Man, S.M., Hopkins, L.J., Nugent, E., Cox, S., Gluck, I.M., Tourlomousis, P., Wright, J.A., Cicuta, P., Monie, T.P., Bryant, C.E. (2014) Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA. 111: 7403-7408.

Man, S.M*., Ekpenyong, A.E*., Tourlomousis, P., Achouri, S., Cammarota, E., Hughes, K., Rizzo A., Ng, G., Wright, J.A., Cicuta, P., Guck, J., Bryant, C.E. (2014) Actin polymerization as a key innate immune effector mechanism to control Salmonella infection. Proc Natl Acad Sci USA. 111:17588–17593. *Co-first author.

  • Featured in Nature Reviews Immunology: Research Highlights: Leavy, O. (2015) Stiffening up defences against Salmonella. Nature Reviews Immunology. 15:4.
  • Recommended by Faculty of 1000 (F1000).

Zaki, M.H, Man, S.M., Vogel, P., Lamkanfi, M., Kanneganti, T.D. (2014) Salmonella exploits NLRP12–dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci USA. 111:385-90.

  • Recommended by Faculty of 1000 (F1000).

Kuriakose, T., Man, S.M., Malireddi, R.K.S., Karki, R., Kesavardhana, S., Place, D.E., Neale, G., Vogel, P., Kanneganti, T.D. (2016) ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science Immunology. 1:aag2045.

  • Featured in Cell Host & Microbe: Previews: Clancy, D.M., Martin S.J. (2016) Getting a gRIP on Flu by Casting the DAI. Cell Host & Microbe. 20:552–554.

Qi, X*.,  Man, S.M*., Malireddi, R.K.S., Karki, R., Lupfer, C., Gurung, P., Neale, G., Guy, C.S., Lamkanfi, M., Kanneganti, T.D. (2016) Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. Journal of Experimental Medicine. 213:2081-2097. *Co-first author.

Karki, R., Man. S.M., Malireddi, R.K.S., Gurung, P., Vogel, P., Lamkanfi, M., Kanneganti, T.D. (2015) Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection. Cell Host & Microbe. 17:357-368.

  • Featured in Cell Host & Microbe: Previews: Tomalka, J., Hise, A.G. (2015) Inflammasomes in aspergillosis – It takes two to tango. Cell Host & Microbe. 17:290-292.
  • Recommended by Faculty of 1000 (F1000).

 

SELECTED REVIEWS

Man, S.M., Kanneganti, T.D. (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nature Reviews Immunology. 16:7-21.

Man, S.M. (2018) Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nature Reviews Gastroenterology & Hepatology. 15:721–737.

Man, S.M. (2011) The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology. 8:669-685.

Man, S.M., Kaakoush, N.O., Mitchell, H.M. (2011) The role of bacteria and pattern-recognition receptors in Crohn’s disease. Nature Reviews Gastroenterology & Hepatology. 8:152-168.

Pandey, A*., Shen, C*., Feng, S*., Man, S.M. (2021) Cell biology of inflammasome activation. Trends in Cell Biology doi: 10.1016/j.tcb.2021.06.010. *Co-first author.

Enosi Tuipulotu, D., Mathur, A., Ngo, C., Man, S.M. (2021) Bacillus cereus: epidemiology, mechanisms of disease and host-pathogen interactions. Trends in Microbiology. 29:458-471.

Xue, Y*., Enosi Tuipulotu, D*., Tan, W.H., Kay, C., Man, S.M. (2019) Emerging activators and regulators of inflammasomes and pyroptosis. Trends in Immunology. 40:1035-1052. *Co-first author.

Kaakoush, N.O., Castaño Rodriguez, N., Man, S.M., Mitchell, H.M. (2015) Is Campylobacter to esophageal adenocarcinoma as Helicobacter is to gastric adenocarcinoma? Trends in Microbiology. 23:455-462.

Publications

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Updated:  28 October 2021 / Responsible Officer:  Director (Research Services Division) / Page Contact:  Researchers