Project Summary The parent grant, 2R35GM119770, (“Multi-cellular and multi-scale systems modeling to understand the dynamics of the human immune system in interdisciplinary applications”) supports my research program, which aims to identify how the immune system can be rewired en masse to elicit higher-order decision-making while still enabling the system to remain otherwise “healthy.” To this end, we are leveraging a highly interdisciplinary research team (computational and experimental immunologists, software engineers, and education researchers) and collaborators to build a Virtual Immune System -- a multi-scale, multi-approach computational framework to understand better the complex dynamical nature of the immune system, identify more accurate multi-dimensional biomarkers, and identify safe and effective treatments within a reasonable time and cost. To this end, we have been building a comprehensive model of the immune system, that integrates knowledge and data across several scales of biological organization, including metabolism, gene regulation, signal transduction, and communication among the different types of immune cells. In addition to expanding the Virtual Immune system, my program continues to develop methods and technologies for data-driven model construction, visualization, computation, real-time simulations, and reproducibility to advance multi-scale modeling of the immune system and beyond, including a cloud-based collaborative modeling software, Cell Collective. This supplement will enable us to generate new high-quality data under consistent conditions that will be used to significantly improve the quality and accuracy of the Virtual Immune System model. The model, along with the data, will be made available to the community through our computing infrastructure.

NARRATIVE The proper response of the immune system to pathogens is governed by complex, network-like interactions among various types of cells and their associated communication mediators. The parent grant enables us to work towards the development of a “Virtual Immune System” -- a multi-cellular and multi-scale model of the human immune system -- to study the properties of the immune system, investigate immune-related diseases, and make predictive modeling software technologies more accessible to the broad scientific community (including immunologists, computational biologists, and translational researchers). This supplement will enable us to generate more high-quality and consistent data needed to develop an accurate computational model of the human immune system.