Abstract: Computational and mathematical approaches when combined with experimentation can provide unique insights into mechanisms driving immunity to pathogens and formation of inflammatory and autoimmune pathology.  Immune responses occur in specialised microenvironments where stochastic interactions between different immune cells and secreted factors (cytokines/chemokines), lead to the emergence of immune responses.  These processes can be simulated using multiscale agent based models reproducing spatial and temporal aspects of the biology.  In this talk I will discuss the modelling process, using principles from systems engineering to develop transparent models using a suite of argumentation, statistical analysis and visualisation tools.  These tools permits both parameterisation of complex models and effective communication between experimental biologists and software engineers.  As an experimental immunologist my research focuses is on how immune microenvironments are established, how they remodel during infection and how cellular interactions drive immune responses.  In this talk I will discuss two examples where we have used a cyclical approach of hypothesis driven multi-scale agent based model with experimentation to develop new insights into immune tissue development and emergence of autoimmune disease pathology.

Select recent publications:

Using argument notation to engineer biological simulations with increased confidence. K.Alden, P.S.Andrews, F.A.C.Polack, H.Veiga-Fernandes, M.C.Coles, J.Timmis. Journal of the Royal Society Interface. doi: 10.1098/rsif.2014.1059

Determining Disease Intervention Strategies Using Spatially Resolved Simulations. M. Read, P. Andrews, J. Timmis, R. Williams, R. Greaves, H. Sheng, M. Coles and V. Kumar. PLoS ONE 8(11): e80506. doi:10.1371/journal.pone.0080506

SPARTAN: A Comprehensive Tool for Understanding Uncertainty in Simulations of Biological Systems. K. Alden, M. Read, J. Timmis, P.S. Andrews, H. Veiga-Fernandes, M.C. Coles. PLoS Comput Biol 9(2): e1002916. doi:10.1371/journal.pcbi.1002916

Differential RET signaling responses orchestrate lymphoid and nervous enteric system development. A. Patel, N. Harker, L. Moreira-Santos, M. Ferreira, K. Alden, J. Timmis, K. Foster, A. Garefalaki, P. Pachnis, P.S. Andrews, H. Enomoto, J. Milbrandt, V. Pachnis, M.C. Coles, D. Kioussis, H. Veiga-Fernandes. Science Signalling, Volume 5, Issue 235. doi: 10.1126/scisignal.2002734

Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs. K. Alden, J. Timmis, P.S. Andrews, H. Veiga-Fernandes, M.C Coles. Frontiers in Immunology. Volume 3:172. doi: doi: 10.3389/fimmu.2012.00172.