Mathematics and the immune system

A cornerstone of the body's defenses is the adaptive immune response. When exposed to foreign material, it generates a sizable collection of cells specific to the given infection through a process called clonal selection. While the overall population dynamics of this response is known, how individual cells make decisions to divide, fight or die is poorly understood. Enhancing our understanding of cellular decision-making processes is key to manipulating immune response to enhance protection or damp auto-immunity.

Since the introduction of Clonal Selection Theory in 1959 by the Australian Nobel Laureate, Macfarlane Burnet, and the identification of lymphocytes as key players in immunity, much evidence has been garnered as to the behavior of the immune response. Recent advances in quantitative experimental technologies are revealing ever more involved patterning in this system that no longer fit simple descriptions. In conjunction with experimental partners world-wide, members of the Hamilton Institute are applying mathematical methodologies to help pick apart and decipher this complex system, which is so significant for human health.

B Lymphocyte
B cells from a Blimp FR mouse, transgenic for Blimp1-GFP (green, cytoplasmic) and Fucci Red (nuclear, G1 phase of the cell cycle), stained with IgG1-APC (blue, on membrane surface). Scale bar is 10um. Image courtesy of Jie H. S. Zhou of the Hodgkin Lab., WEHI.

We are developing theories, heavily informed by cutting edge experimental evidence, based on a paradigm shift: that cells actively exploit, rather than suffering from, randomness to achieve their goals and this is not inconsistent with repeatable, predictable population-level dynamics. The primary aim of this theory is to gain an operational understanding of the immune response and its regulators at the cellular level. The ultimate hope is that it will enable extrapolations of medical significance.

B Lymphocyte
B cell from a Blimp FR mouse, transgenic for Blimp1-GFP (green, cytoplasmic) and Fucci Red (nuclear, G1 phase of the cell cycle), Scale bar is 10um. Image courtesy of Jie H. S. Zhou of the Hodgkin Lab., WEHI.

Current Projects

"Quantitative T Cell Immunology", European Union Marie Curie ITN, 2013-2017.

Co-PIs at: BTS, Charite, DKFZ, INSERM, Leeds (coordinator), NKI, NUIM (Hamilton Institute), NUIG, Pasteur UCL, Utrecht and UMCU. Associated partners at: AstraZeneca, Microsoft Research Cambridge, TalaveraScience, Unilever, Universidad de Vigo and WEHI.

"Indo-European Research Network in Mathematics for Health and Disease", European Union Marie Curie IRSES, 2013-2017.

Co-PIs at: Basel, Leeds (coordinator), NUIM, Pontificia Comillas, UCL, Utrecht, Vigo. Associated partners: Hyderabad, Institute of Math Sciences Chennai, IIS Bangalore, Jawaharlal Nehru, MIT, National Institute of Immunology (Delhi) UBC, WEHI.

"Single cell lineage tracing to understand hematopoietic development and differentiation", Human Frontier Science Program Grant, 2012-2015.

Co-PIs at: Drexel, NUIM (Hamilton Institute), NKI and WEHI.