The Human Immunology laboratory is focused on the autoimmune disease type 1 diabetes. Broadly, we have two goals. The first is to understand how and why insulin-producing beta cells are attacked by the immune system’s T cells – which is the ultimate cause of type 1 diabetes. Our second goal is to use this information to develop safe and effective ways to stop disease progression for people at high risk. Our long-term objective is to reverse type 1 diabetes in people who have been recently diagnosed.

Currently, the focus of our work is unravelling the specificity of the autoimmune responses that cause people to develop type 1 diabetes. We achieved a world-first when we isolated and analysed human islet-infiltrating T cells from deceased organ donors who suffered from type 1 diabetes. This invaluable resource has allowed us to understand the ‘nuts and bolts’ of the autoimmune response in the part of the body that is affected.

A second major focus is to develop and validate new tests that can be used to monitor the autoimmune response that causes type 1 diabetes. This works will lead us to develop safe and effective therapies for the prevention, or reversal, of type 1 diabetes.

Current research projects

  • Why doesn’t everyone get type 1 diabetes?
    What antigens do human islet infiltrating CD4+ T cells ‘see’?
    Do islet infiltrating CD4+ T cells recognise epitopes formed by post-translational modification?
    Identifying the antigens and epitopes seen by human islet-infiltrating CD8+ T cells
    Identifying the antigens and epitopes seen by human islet-infiltrating CD8+ T cells

People

Stuart Mannering
Stuart Mannering

Head, Human immunology

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smannering@svi.edu.au

+61 3 9231 2480

Available for Student Supervision

Matthew Lacorcia

Research Officer, Human Immunology Laboratory

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mlacorcia@svi.edu.au

Available for Student Supervision

Dillon Jevon

Postdoctoral Research Officer, Human Immunology

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dillon.jevon@svi.edu.au

Available for Student Supervision

  • Miha Pakusch, Senior Research Assistant
  • Eleonora Tresoldi, Research Assistant
  • Miha Pakusch, Research Assistant
  • Abby Foster, Research Assistant
  • Narelle Shen, Research Manager
  • Saghar Mehrban, PhD student

Student Projects

Hons/Masters/PhD

Do CD4+ T cells that infiltrate human pancreatic islets in type 1 diabetes recognise enterovirus proteins?

Lab: Human Immunology

Supervisor(s): Associate Professor Stuart Mannering

Diseases focus: Immunology
Hons/Masters/PhD

What hybrid insulin peptides (HIIPs) are recognised by human islet-infiltrating CD4+ T cells in type 1 diabetes?

Lab: Human Immunology

Supervisor(s): Associate Professor Stuart Mannering

Diseases focus: Immunology
Hons/Masters/PhD

Measuring islet-antigen specific regulatory T-cell (Treg) function in human type 1 diabetes.

Lab: Human Immunology

Supervisor(s): Associate Professor Stuart Mannering

Diseases focus: Immunology
Honours/Masters

Dissecting the autoimmune pathogenesis of human type 1 diabetes

Lab: Human Immunology

Supervisor(s): Associate Professor Stuart Mannering

Diseases focus: Immunology

Selected publications

M.T. Tran, P. Faridi, J. J. Lim, Y. T. Ting, G. Onwukwe, P. Bhattacharjee, C. M. Jones, E. Tresoldi, F. J. Cameron, N. L. La Gruta, A. W. Purcell, S. I. Mannering, J. Rossjohn, and H. H. Reid. “T Cell Receptor Recognition of Hybrid Insulin Peptides Bound to Hla-Dq8.” Nat Commun 12, no. 1 (25 Aug 2021): 5110. dx.doi.org/10.1038/s41467-021-25404-x.

M.So, C. M. Elso, E. Tresoldi, M. Pakusch, V. Pathiraja, J. M. Wentworth, L. C. Harrison, B. Krishnamurthy, H. E. Thomas, C. Rodda, F. J. Cameron, J. McMahon, T. W. H. Kay, and S. I. Mannering. “Proinsulin C-Peptide is an Autoantigen in People with Type 1 Diabetes.” Proc Natl Acad Sci U S A 115, no. 42 (16 Oct 2018): 10732-37. dx.doi.org/10.1073/pnas.1809208115.

T.Delong, T. A. Wiles, R. L. Baker, B. Bradley, G. Barbour, R. Reisdorph, M. Armstrong, R. L. Powell, N. Reisdorph, N. Kumar, C. M. Elso, M. DeNicola, R. Bottino, A. C. Powers, D. M. Harlan, S. C. Kent, S. I. Mannering, and K. Haskins. “Pathogenic Cd4 T Cells in Type 1 Diabetes Recognize Epitopes Formed by Peptide Fusion.” Science 351, no. 6274 (2016-02-12 00:00:00 2016): 711-14. dx.doi.org/10.1126/science.aad2791.

V.Pathiraja, J. P. Kuehlich, P. D. Campbell, B. Krishnamurthy, T. Loudovaris, P. T. Coates, T. C. Brodnicki, P. J. O’Connell, K. Kedzierska, C. Rodda, P. Bergman, E. Hill, A. W. Purcell, N. L. Dudek, H. E. Thomas, T. W. Kay, and S. I. Mannering. “Proinsulin-Specific, Hla-Dq8, and Hla-Dq8-Transdimer-Restricted Cd4+ T Cells Infiltrate Islets in Type 1 Diabetes.” Diabetes 64, no. 1 (Jan 2015): 172-82. dx.doi.org/10.2337/db14-0858.

S.I. Mannering, J. A. Dromey, J. S. Morris, D. J. Thearle, K. P. Jensen, and L. C. Harrison. “An Efficient Method for Cloning Human Autoantigen-Specific T Cells.” J Immunol Methods 298, no. 1-2 (Mar 2005): 83-92. dx.doi.org/S0022-1759(05)00009-8 [pii]10.1016/j.jim.2005.01.001.

S.I. Mannering, J. S. Morris, K. P. Jensen, A. W. Purcell, M. C. Honeyman, P. M. van Endert, and L. C. Harrison. “A Sensitive Method for Detecting Proliferation of Rare Autoantigen-Specific Human T Cells.” J Immunol Methods 283, no. 1-2 (Dec 2003): 173-83. dx.doi.org/S0022175903003661 [pii].

Related News

New funding in support of type 1 diabetes research
News

December 2024

New funding in support of type 1 diabetes research

Head of SVI's Human Immunology Lab Associate Professor Stuart Mannering has received $150k grant from JDRF for the commercialisation of his research under their new program called SPARC.