Prof Phil Hodgkin, Lab Head | WEHI Researcher Profile

About

Our lab has a long-standing interest in understanding how the immune system operates. By combining experiment and theory we aim to identify and codify how logical cellular operations can be altered and controlled by a range of signals. The results lead to powerful, predictive quantitative models that improve our understanding and provide new tools to dissect the system further. Our target is the immune system, but our developing and improving theories apply equally to blood cell development and cancer biology.

Our immune system is critical for health, but its complex operation makes it difficult to understand and control. This hurdle is important as immune dysfunction is a major contributor to human diseases, accounting for a significant health burden. In the Hodgkin lab we aim to understand how the cells of the immune system make decisions that underlie immune health or head down the path of disease causing ‘errors’ that lead to conditions such as autoimmunity or allergies. By combining experiment and theory we identify how cellular functions are altered and controlled by a range of cell communication signals, alone and in combination. The results help formulate predictive, quantitative models that operate at cell and molecular level to improve our understanding of immunity and provide new tools to dissect the immune system further.

Our results to date support a revision of the foundational theory for the adaptive immune response that incorporates ideas from many fields, including statistical physics. This is because we discovered cells use randomising processes to allocate, cells to different tasks. We test and inform the developing framework by experiments such as video microscopy and time series division tracking to watch T and B cells in the act of making decisions and modifying their behaviour.

Our resulting mathematical models and quantitative methods allow us to measure differences between individuals and provide insights into the complex causes of underlying immune dysfunction.

Building and testing this theory forms one of the major goals of the Snow Centre for Immune Health. Within the Centre we are revising and updating clonal selection theory to develop methods to assess the health of immune cells sampled from individuals. Results can be used to build personalised models of immune decision-making and help identify complex causes of immune errors as well as provide insights into selecting appropriate treatments.

Education

Publications

Selected publications from Prof Phil Hodgkin

Biemond M, Vremec D, Gray DH, Hodgkin PD, Heinzel S. Programmed death receptor 1 (PD‐1) ligand Fc fusion proteins reduce T‐cell proliferation in vitro independently of PD‐1. Immunology and Cell Biology. 2024;102(2):10.1111/imcb.12714

Heinzel S, Cheon H, Belz GT, Hodgkin PD. Survival and division fate programs are preserved but retuned during the naïve to memory CD8+ T‐cell transition. Immunology and Cell Biology. 2024;102(1):10.1111/imcb.12699

Farchione AJ, Cheon H, Hodgkin PD, Bryant VL. Quantifying Human Naïve B Cell Proliferation Kinetics and Differentiation in Controlled In Vitro Cell Culture. Methods in Molecular Biology. 2024;2826:10.1007/978-1-0716-3950-4_13

Hodgkin PD. Kevin Lafferty and the lymphocyte costimulator: theory and practice in Canberra. Immunology and Cell Biology. 2023;101(8):10.1111/imcb.12683

Robinson MJ, Ding Z, Dowling MR, Hill DL, Webster RH, McKenzie C, Pitt C, O’Donnell K, Mulder J, Brodie E, Hodgkin PD, Wong NC, Quast I, Tarlinton DM. Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan. Immunity. 2023;56(7):10.1016/j.immuni.2023.04.015

Kong IY, Trezise S, Light A, Todorovski I, Arnau GM, Gadipally S, Yoannidis D, Simpson KJ, Dong X, Whitehead L, Tempany JC, Farchione AJ, Sheikh AA, Groom JR, Rogers KL, Herold MJ, Bryant VL, Ritchie ME, Willis SN, Johnstone RW, Hodgkin PD, Nutt SL, Vervoort SJ, Hawkins ED. Epigenetic modulators of B cell fate identified through coupled phenotype-transcriptome analysis. Cell Death & Differentiation. 2022;29(12):10.1038/s41418-022-01037-5

Robinson MJ, Dowling MR, Pitt C, O’Donnell K, Webster RH, Hill DL, Ding Z, Dvorscek AR, Brodie EJ, Hodgkin PD, Quast I, Tarlinton DM. Long-lived plasma cells accumulate in the bone marrow at a constant rate from early in an immune response. Science Immunology. 2022;7(76):10.1126/sciimmunol.abm8389

Horton MB, Cheon H, Duffy KR, Brown D, Naik SH, Alvarado C, Groom JR, Heinzel S, Hodgkin PD. Lineage tracing reveals B cell antibody class switching is stochastic, cell-autonomous, and tuneable. Immunity. 2022;55(10):10.1016/j.immuni.2022.08.004

Zotos D, Quast I, Li-Wai-Suen CSN, McKenzie CI, Robinson MJ, Kan A, Smyth GK, Hodgkin PD, Tarlinton DM. The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21. Nature Communications. 2021;12(1):10.1038/s41467-021-27477-0

Naik S, Tian L, Tomei S, Schreuder J, Weber T, Amman-Zalcenstein D, Lin D, Tran J, Audiger C, Bahlo M, Chu M, Diakumis P, Gouil Q, Hilton A, Jarratt A, Willson T, Kats L, kelly M, Pang ES, O’Keeffe M, Patton T, Sargeant T, Su S, Hodgkin P, Ng A, Ritchie M. 3104 – CLONAL MULTI-OMICS METHODS SIS-SEQ AND SIS-SKEW REVEAL BCOR AS A NEGATIVE REGULATOR OF EMERGENCY DENDRITIC CELL DEVELOPMENT. Experimental Hematology. 2021;100:10.1016/j.exphem.2021.12.321