Form Leads to Function: Multi-scale modelling of Lymph Node Architecture in Response to Vaccine Adjuvants

Although vaccines have been in use for over 250 years, the mechanisms driving protective immunity are not fully understood. The continual emergence of potentially lethal human and domestic animal pathogens, and the need to generate protective vaccines against chronic bacterial and viral infections requires a better understanding of mechanisms of action to develop the next generation of vaccines. Vaccine immune responses involve a complex interplay between the highly diverse immune repertoire of T and B cells, stromal fibroblasts and innate immune cells in tissue draining lymph nodes (LN). We have shown during the immune response, LNs rapid remodel in a process dependent on the type of vaccine adjuvant, regulating the type, duration and specificity of the immune response.
We and others have developed multi-scale agent-based models of the lymph node to study immune cell dynamics during vaccine responses and formation of LN microenvironments. In this project we aim to use datasets including imaging, cytometry and gene expression from different adjuvants to design, develop and validate computational models. We have developed tool kits to both visualise model outputs and statistically analyse parameter space in multi-scale computational models. Through combining neural network emulation with genetic evolutionary algorithms to perform multi-objective optimisation, we aim to identify optimal LN architectures in silico that stimulates protective immune responses permitting better vaccine design.
Benefits and project impact: Developing a robust evidence-based model of the vaccine mediated immune responses has an essential role in understanding how normal animal and human lymph node microenvironments stimulate optimal immune responses to provide long term protection. This has the potential to permit the development of more effective vaccines for infectious organisms and cancer.
Skills Training: The student will have the opportunity to learn key interdisciplinary skills in mathematics, computer programming, data analysis and in molecular and cellular immunology. The student will be jointly based in the Kennedy Institute of Rheumatology and the Mathematical Institute with academic and translational skills training opportunities. Interdisciplinary seminars at the Kennedy and Jenner Institutes host world leading seminars in immunology and vaccine development, the Wolfson Centre for Mathematical Biology in mathematical biology. Simomics is an SME based in York and has previously developed Virtual Disease Laboratories to develop therapeutics for Leishmaniasis (LeishSim) and is working on models to study immune responses. Through this collaboration the student will be able to utilise tools developed by Simomics including virtual laboratories, model development syntax languages and statistical tool kits to assist in the generation and confidence in the lymph node model. Development of a robust evidence-based lymph node model will provide a platform to simulate how to generate optimal vaccine responses that have a critical role in healthy living and aging.
Industrial Secondment: The secondment will take place at Simomics offices which based at the York Science Park in York. York is a highly vibrant academic city that provides a beautiful environment. The student will be based in a group of software developers who have extensive experience in software development and computational modelling.