Our lab investigates the role of inflammation in infectious diseases and cancer. Pattern-recognition receptors are 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 unveil how cells recognise bacteria, viruses and parasites, and how these sensors shape the overall immune response. We investigate the role of disease-fighting immune proteins in destroying multidrug resistant pathogens or superbugs. We also study the molecular basis by which uncontrolled inflammation can lead to the development of cancer, autoimmunity and inflammatory diseases.

We welcome applications from PhD students, research assistants and Postdoctoral Fellows. Fully-funded PhD scholarships are available. E-mail Si Ming (siming.man@anu.edu.au) for further information regarding project details and position availability.

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 and NHMRC Leadership 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 for producing multiple highly-cited papers in the last decade that rank in the top 1% by citations for field and year in the Web of Science™.

Awards and recognition:

• NHMRC Investigator Grant Level 1 (2024)
• Fellow, The Royal Society of NSW (2023)
• Australian Academy of Science Gottschalk Medal (2023)
• UNSW Alumni Award for Research & Teaching Achievements (2023)
• ANU College of Health & Medicine Dean's Commendation for Excellence in Supervision (2023)
• Frank Fenner Prize for Life Scientist of the Year, Prime Minister's Prizes for Science (2022)
• CSL Centenary Fellowship (2021)
• Australian Society for Medical Research (ASMR) Peter Doherty Leading Light Award (2020)
• Australian Society for Biochemistry & Molecular Biology (ASBMB) Eppendorf Edman Early Career Award (2020)
• The Australian National University Vice-Chancellor's Award for Early Career Academic Excellence (2020)
• Commonwealth Health Minister's Medal for Excellence in Health and Medical Research (2019)
• The Royal Society of NSW Edgeworth David Medal (2019)
• NHMRC Research Excellence Award for the highest-ranked Career Development Fellowship Biomedical Level 1 (2019)
• American Association of Immunologists (AAI) Pfizer-Showell Award (2019)
• Fellow, The Australian Society for Microbiology (ASM) (2019)
• Australian Society for Microbiology (ASM) Jim Pittard Early Career Award (2017)
• American Association of Immunologists (AAI) Thermo Fisher Trainee Achievement Award (2016) 
• International Cytokine & Interferon Society (ICIS) Milstein Young Investigator Award (2016)
• NHMRC Research Excellence Award for the highest-ranked Early Career Fellowship (2015)

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

Possible project areas we have available include:

• Uncovering how host cells, such as macrophages, recognise and kill human pathogens, including bacteria (such as Salmonella, Clostridium, Listeria, Francisella, and Bacillus) and viruses (Influenza, MCMV, HSV).
• Unravelling the molecular mechanisms of inflammasome formation.
• Understanding the role of innate immune sensors in regulating the development of cancer, such as small intestinal cancer, colorectal (bowel) cancer, and melanoma, and the composition of the gut microbiota.
• Identifying novel activators and inhibitors of the immune system to prevent and treat infection, autoinflammatory diseases and cancer.

Current and past PhD students:

2017-2021: Dr. Anukriti Mathur, PhD thesis title: Microbial activators of the inflammasome

• Awarded the Sidney & Joan Pestka Graduate Award from the International Cytokine & Interferon Society, 2019
• Awarded the Australian Society for Microbiology Nancy Millis Award NSW/ACT, 2019
• Awarded the Australian Society for Biochemistry & Molecular Biology (ASBMB) Fellowship, 2020
• Awarded the Cells PhD Thesis Award, 2021
• Awarded an Australian and New Zealand Society for Immunology Career Advancement Award (Postgraduate), 2021
• Awarded the Frank Fenner Medal for the most outstanding PhD thesis submitted in The John Curtin School of Medical Research, 2022
• Work published in Nature Microbiology, Nature Communications (x2) and EMBO Reports
  

2018-2022: Dr. Shouya Feng, PhD thesis title: Guanylate-binding proteins as mediators of inflammasome activation in response to bacterial infection

• Awarded the Cold Spring Harbor Best Poster Prize, 2019
• Awarded the Australian Society for Microbiology NSW/ACT Branch Student Travel Award, 2022
• Work published in Nature Communications (x2), The EMBO Journal, Trends in Biochemical Sciences

2018-2022: Dr. Abhimanu Pandey, PhD thesis title: The role of cytosolic nucleic acid sensors in colitis and intestinal cancer

• Awarded a Royal Society of NSW Bicentennial Early Career Research and Service, 2023
• Awarded the Dewar-Milne Prize in Immunology is awarded annually for the most outstanding PhD thesis in the field of Immunology submitted in JCSMR, 2023
• Awarded the Australian Society for Biochemistry & Molecular Biology (ASBMB) Fellowship, 2024
• Work published in Science Advances (x2), Trends in Cell Biology, and Nature Communications (x3)
  

2018-2022: Dr. Cheng Shen, PhD thesis title: Inflammasomes in tumourigenesis

• Work published in Trends in Cell Biology, Cell Research, and Yale Journal of Biology & Medicine

2022-2025: PhD thesis title: DNA sensors in infection and immunity

• Awarded the Royal Society of NSW Scholarship, 2022

2022-2025: PhD thesis title: LPS sensing in the activation of immune responses

2023-2025: PhD thesis title: Guanylate-binding proteins as cytosolic pattern-recogntion receptors

2023-2025: PhD thesis title: Bacterial activators of inflammasomes

2024-2026: PhD thesis title: Novel components of inflammasomes

2024-2026: PhD thesis title: Guanylate-binding proteins in tumour immunology

Current and past theses of Honours students:

• 2018: Molecular mechanisms of inflammasome activation by enterotoxins of the foodborne pathogen Bacillus cereus, Awarded First Class Honours

• 2018-2019: Transmembrane regions of the pore-forming toxin Haemolysin BL are required for inflammasome activation but not membrane binding, Awarded First Class Honours and the University Medal

•  2019: Clostridium perfringens is a novel activator of the NLRP3 inflammasome, Awarded First Class Honours and the University Medal

• 2020-2021: The molecular mechanism of alpha-toxin-induced inflammasome activation in response to Clostridium septicum infection, Awarded First Class Honours and the University Medal

•  2021: DNA sensing in Listeria infection, Awarded First Class Honours. Awarded an ANU PhD Scholarship.

•  2022: Guanylate-binding proteins as antimicrobial peptides, Awarded First Class Honours. Awarded a 2023 Rhodes Scholarship to The University of Oxford.

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.

Jing, W., Lo Pilato, J., Kay, C., Feng, S., Enosi Tuipulotu, D., Mathur, A., Shen, C., Ngo, C., Zhao, A., Miosge, L.A., Ali, S.A., Gardiner, E.E., Awad, M.M., Lyras, D., Robertson, A.A.B., Kaakoush, N.O.,  Man, S.M^‡.  (2022) Clostridium septicum alpha-toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins. Science Immunology. 7:eabm1803. ^‡ Senior author.

• Altmetric Score: 548 (99th percentile)

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.

Pandey, A., Shen, C., Feng, S., Enosi Tuipulotu, D., Ngo, C., Liu, C., Kurera, M., Mathur, A., Venkataraman, S., Zhang, J., Talaulikar, D., Song, R., Wong, J.J-L., Teoh, N., Kaakoush, N.O., and Man, S.M. ^‡ (2024). Ku70 senses cytosolic DNA and assembles a tumor-suppressive signalosome. Science Advances. 10(4):eadh3409. ^‡ Senior author.

• Covered by the New York Post, 7 News National, 9 News National, and 170 media outlets.
• Altmetric Score: 818 (99th percentile).

 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, Herald Sun, and 41 media outlets.
• Altmetric Score: 159 (98th percentile)

Feng, S.,* Enosi Tuipulotu, D.,* Pandey, A.,  Jing, W., Shen, C., Ngo, C., Tessema, M.B., Li, F-J., Fox, D., Mathur, A., Zhao, A., Runli Wang¹, Pfeffer, K., Degrandi, D., Yamamoto, M., Reading, P.C., Burgio, G., Man, S.M^‡. (2022) Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling. Nature Communications. 13:4395. *Co-first author. ^‡ Senior author.

• Covered by Cosmos Magazine, The Epoch Times, The West Australian, AAP, and 131 media outlets across print and online.

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.

Luu, L.,* Pandey, A.,* Paramsothy, S.,* Ngo, C., Castano-Rodriguez, N., Liu, C., Kamm, M., Borody, T., Man, S.M., Kaakoush, N.O. (2024) Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice. Nature Communications. 15:2645. *Co-first 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).

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).

Enosi Tuipulotu, D.,* Feng, S.,* Pandey, A., Zhao, A., Ngo, C., Mathur, A., Lee, J., Shen, C., Fox, D., Xue, Y., Kay, C., Kirkby, M., Lo Pilato, J., Kaakoush, N.O.,  Webb, D., Rug, M., Robertson, A.A.B., Tessema, M.B., Pang, S., Degrandi, D., Pfeffer, K., Augustyniak, D., Blumenthal, A., Miosge, L.A., Brüstle, A., Yamamoto, M., Reading, P.C., Burgio, G.,  and Man, S.M. ^‡ (2023) Immunity against Moraxella catarrhalis requires guanylate-binding proteins and inflammasomes. The EMBO Journal. 42:e112558. *Co-first author. ^‡ Senior author.

Mathur, A.,* Kay, C.,* Xue, Y., Pandey, A., Lee, J., Jing, W., Enosi Tuipulotu, D., Lo Pilato, J., Feng, S., Ngo, C., Zhao, A., Shen, C., Rug, M., Miosge, L.A., Atmosukarto, I.I., Price, J.D., Ali, S.A., Gardiner, E.E., Robertson, A.A.B., Awad, M.M., Lyras, D., Kaakoush, N.O., and Man, S.M. ^‡ (2023) Clostridium perfringens virulence factors are nonredundant activators of the NLRP3 inflammasome. EMBO Reports. e54600. *Co-first author. ^‡ Senior author.

• Covered by The Canberra Times, West Australia, AAP and 108 media outlets across print and online.
  

SELECTED REVIEWS

Man, S.M., Jenkins, B.J. (2022) Context-dependent functions of pattern recognition receptors in cancer. Nature Reviews Cancer. 22:397-413.

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.

Kirkby, M., Enosi Tuipulotu, D., Feng, S., Lo Pilato, J., Man, S.M. (2023) Guanylate-binding proteins: mechanisms of pattern-recognition and antimicrobial functions. Trends in Biochemical Sciences. 48:883-893.

Pandey, A*., Shen, C*., Feng, S*., Man, S.M. (2021) Cell biology of inflammasome activation. Trends in Cell Biology. 31:924-939. *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.