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Institute of Immunity and Transplantation

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Computational Immunology

This interdisciplinary field applies computational and mathematical approaches to study the immune system's complexity and its interactions with pathogens, diseases, and therapies.

Our work

At the IIT, we also use artificial intelligence approaches to crack the code of the adaptive immune system. We predict which pathogens are recognised by randomly generated antigen receptors on T and B cells.

By combining computational techniques with immunology, we can advance our understanding of how the immune system works and develop more effective strategies for diagnosing and treating immune-related disorders.

Projects

Cellular mechanisms controlling T cell immunity in non-lymphoid tissues

Following resolution of immune responses, memory T cells take up residence within the tissue at the site of the primary infection. These cells provide the first line of defence by the adaptive immune system. Our work combines novel fate reporter mouse strains with mathematical models to investigate the cellular mechanisms governing generation and maintenance of these tissue resident T cells.

Lead Investigators

  • Prof. Benedict Seddon (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Prof. Andy Yates (Columbia University, USA)
  • Prof. Donna Farber (Columbia University, USA)

Funding

  • National Institutes for Health, US
Cellular mechanisms controlling generation and maintenance of T cell memory

Following resolution of immune responses, T cells that recognise invading pathogen survive and become memory T cells. How these cells are generated and maintained between infections/exposure remains poorly defined. We aim to use novel fate reporter mouse strains and mathematical models to investigate the mechanisms governing generation and maintenance of T cell immunological memory, which is essential to prevent re-infection upon further exposure to pathogen.

Lead Investigators

  • Prof. Benedict Seddon (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Prof. Andy Yates (Columbia University, US)

Funding

  • National Institutes for Health, US
Generation and maintenance of marginal zone B cells

Efficient resolution of systemic infections relies on the rapid production of antibodies. A key element of this protection is mediated by B cells that reside primarily in the marginal zone (MZ) of the spleen. Our work combines novel fate reporter mouse strains with mathematical models to investigate the mechanisms governing generation and maintenance of MZ B cells.

Lead Investigators

  • Prof. Benedict Seddon (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Dr Sanket Rane (Columbia University, US)
  • Prof. Lothar Strobl (Helmholtz Zentrum München)
  • Prof. Andy Yates  (Columbia University, US)

Funding

  • National Institutes for Health, US
Collective computation and regulation in the immune system

To provide efficient defence, immune systems dynamically adapt to the pathogens they encounter. We mathematically model the collective mechanisms that regulate these dynamical processes from bacteria to human to understand the computational principles they implement.

Lead Investigator

  • Dr Andreas Tiffeau-Mayer (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Prof. Lucy Walker (Institute of Immunity & Transplantation, UCL)
  • Dr Jennifer Cowan (Institute of Immunity & Transplantation, UCL)
  • Dr Ben Greenbaum (Computational Immuno-Oncology, Sloan-Kettering Cancer Center)
  • Prof. Vijay Balasubramanian (Department of Physics and Astronomy, U Penn)

Funding

  • Royal Free Charity
Reading the adaptive immune receptor code

The specificity of adaptive immune responses relies on the binding of hyper-variable receptors to diverse ligands. We are using artificial intelligence approaches to reveal the sequence determinants of antibody and T cell receptor binding specificity.

Lead Investigator

  • Dr Andreas Tiffeau-Mayer (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Prof. Benny Chain (Institute of Immunity & Transplantation, UCL)
  • Prof. Hans Stauss (Institute of Immunity & Transplantation, UCL)
  • Prof. Ned Wingreen (Lewis-Sigler Institute for Integrative Genomics, Princeton U)
  • Prof. Curtis Callan (Department of Physics, Princeton U)
  • Prof. Lisa Wagar (Department of Physiology and Biophysics, UC Irvine)

Funding

  • Wellcome Leap
  • National Institute for Health Research
  • Royal Free Charity
Tracking immunity in infectious and autoimmune disease

Sequencing of adaptive immune receptor repertoires allows tracking immune responses at unprecedented depth. We are working on linking repertoire information to outcomes in infectious (SARS-CoV-2 and mycobacterium tuberculosis) and autoimmune (type 1 diabetes) diseases.

Lead Investigator

  • Dr Andreas Tiffeau-Mayer (Institute of Immunity & Transplantation, UCL)

Collaborators

  • Prof. Benny Chain (Institute of Immunity & Transplantation, UCL)
  • Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
  • Prof. Mahdad Noursadeghi (Institute of Immunity & Transplantation, UCL)
  • Prof. Al Leslie (AHRI/UCL)

Funding

  • National Institute for Health Research
  • Royal Free Charity

Our experts

Benedict Seddon

Prof. Benedict Seddon
Immune Cell Homeostasis

Andreas Mayer

Dr Andreas Tiffeau-Mayer
Computational Biology


Funding and partnerships

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Selected publications

  1. Lindeboom RGH, Worlock KB, Dratva LM ... Mayer A, et al (2024). Human SARS-CoV-2 challenge uncovers local and systemic response dynamics. Nature. 2024 Jul;631(8019): 189-198. Erratum in: Nature. 2024 Aug 1.

  2. Lukas E, Hogan T, Williams C, Seddon B, Yates AJ (2023). Quantifying cellular dynamics in mice using a novel fluorescent division reporter system. Front Immunol. 2023 Jul 27;14:1157705.

  3. Mayer A, Callan CG Jr (2023). Measures of epitope binding degeneracy from T cell receptor repertoires. Proc Natl Acad Sci USA. 2023 Jan 24;120(4): e2213264120.

  4. Milighetti M, Peng Y, Tan C ... Mayer A, et al (2023). Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection. iScience. 2023 Jun 16;26(6): 106937.

  5. Rane S, Hogan T, Lee E, Seddon B, Yates AJ (2022). Towards a unified model of naive T cell dynamics across the lifespan. Elife. 2022 Jun 9;11: e78168.

  1. Chen H, Mayer A, Balasubramanian V (2022). A scaling law in CRISPR repertoire sizes arises from the avoidance of autoimmunity. Curr Biol. 2022 Jul 11;32(13): 2897-2907.e5.

  2. Verheijen M, Rane S, Pearson C, Yates AJ, Seddon B (2020). Fate Mapping Quantifies the Dynamics of B Cell Development and Activation throughout Life. Cell Rep. 2020 Nov 17;33(7): 108376.

  3. Mayer A, Zhang Y, Perelson AS, Wingreen NS (2019). Regulation of T cell expansion by antigen presentation dynamics. Proc Natl Acad Sci USA. 2019 Mar 26;116(13): 5914-5919.

  4. Rane S, Hogan T, Seddon B, Yates AJ (2018). Age is not just a number: Naive T cells increase their ability to persist in the circulation over time. PLoS Biol. 2018 Apr 11;16(4): e2003949.