BII: Emergent Mechanisms in Biology of Robustness, Integration & Organization (EMBRIO)

A fundamental requirement for life and survival is that biological systems are robust, and that they maintain function despite external and internal perturbations such as wounding or infection. Integration of signals from multiple inputs (e.g., biochemical, mechanical) is essential to robustness, yet the mechanisms underlying such integration are poorly understood.

The Emergent Mechanisms in Biology of Robustness, Integration, and Organization (EMBRIO) Biology Integration Institute will address this knowledge gap by leveraging state-of-the-art techniques for measuring cellular and tissue remodeling as well as imaging and data processing. The Institute's research will determine how living systems employ signaling molecules and intracellular second messengers (e.g., calcium), from cellular to organismal levels, to integrate signals and develop a coordinated, whole-system response to perturbations.

An understanding of these dynamics and the integrated networks leading to robustness is essential for elucidating how organisms respond to attack and repair wounds. The Institute will lead to a greater understanding of how to support trans-disciplinary and cross-institutional communication and collaboration to advance science and education. Integration of activities will generate innovative curriculum and professional development tools that will be disseminated for broad use via existing NSF program infrastructure.

These tools will facilitate faculty and trainee development of integrated knowledge and research approaches, like computational modeling, which will prepare students to be competitive in the STEM workforce and contribute to new discoveries in Integrative Biology.

Complex biological networks are appreciated as integral components of living systems; however, knowledge about system dynamics, integration of diverse inputs, and mechanisms to coordinate responses across broad scales of space and time is lacking. The EMBRIO Institute will innovatively address this knowledge gap by determining how living systems integrate “orthogonal” signals such as chemical and mechanical stimuli, and as a result of this signal integration, develop responsive phenotypes for survival and function.

The overarching hypothesis is that multimodal signal integration by second messengers, as a conserved Rule of Life, controls and synchronizes the dynamics and organization of the cytoskeleton and cell signaling to restructure cells and tissues in response to stimulation, damage, or attack. The Institute addresses the hypothesis that, as a Rule of Life, this signal integration persists across taxa, leading to emergent behavior shared by the biological systems.

The Institute will study responses to second messengers in biological systems from different kingdoms and over a range of scales, by harnessing big data (e.g., image data, AFM, simulation data) through AI and ML tools to process and interpret the data and bridge simulations across systems. The Institute will develop a unified technology to quantitatively delineate signal integration and the intracellular changes targeted by these signals, and a simulation-based fusion will be developed that takes the measurements and quantifications in one system and directly predicts the responses in other systems.

The innovative approaches employed by the Institute are integrated into pedagogy through cognitive apprenticeship to advance a diverse STEM workforce.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.