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

生命和生存的一个基本要求是生物系统是健壮的，尽管受到外部和内部的扰动，如受伤或感染，它们仍能保持功能。整合来自多个输入（如生化、机械）的信号对鲁棒性至关重要，但人们对这种整合的机制知之甚少。生物学整合研究所（EMBRIO）将利用最先进的技术来测量细胞和组织重塑以及成像和数据处理，从而解决这一知识缺口。该研究所的研究将确定生命系统如何利用信号分子和细胞内第二信使（如钙），从细胞到有机体水平，整合信号并发展协调的，对扰动的全系统响应。了解这些动态和导致鲁棒性的集成网络对于阐明生物体如何应对攻击和修复伤口至关重要。该研究所将使人们更好地了解如何支持跨学科和跨机构的交流与合作，以促进科学和教育。活动的整合将产生创新的课程和专业发展工具，这些工具将通过现有的国家科学基金会项目基础设施广泛传播。这些工具将促进教师和实习生综合知识和研究方法的发展，如计算建模，这将使学生在STEM劳动力中具有竞争力，并为综合生物学的新发现做出贡献。复杂的生物网络被认为是生命系统的组成部分；然而，关于系统动力学的知识，不同输入的集成，以及跨空间和时间尺度协调响应的机制是缺乏的。EMBRIO研究所将通过确定生命系统如何整合“正交”信号（如化学和机械刺激）来创新地解决这一知识鸿沟，并作为这种信号整合的结果，发展出对生存和功能有反应的表型。最重要的假设是，第二信使的多模态信号整合作为一种保守的生命规则，控制和同步细胞骨架和细胞信号的动态和组织，以对刺激、损伤或攻击做出反应，重构细胞和组织。该研究所提出了一种假设，即作为生命的规则，这种信号整合在不同的分类群中持续存在，导致生物系统共有的紧急行为。该研究所将通过利用大数据（如图像数据、AFM、模拟数据），通过人工智能和机器学习工具处理和解释数据，并跨系统进行模拟，研究来自不同王国和不同规模的生物系统对第二信使的反应。该研究所将开发一种统一的技术来定量描述信号集成和这些信号所针对的细胞内变化，并将开发一种基于模拟的融合技术，在一个系统中进行测量和量化，并直接预测其他系统的响应。研究所采用的创新方法通过认知学徒制融入教学法，以促进多样化的STEM劳动力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.