Targeting evolutionarily encoded molecular antennae to wirelessly reprogram systemic metabolism

靶向进化编码的分子天线以无线方式重新编程全身代谢

• 批准号: 10687635
• 负责人: Calvin Carter
• 金额: $ 139.95万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-11 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687635
• 关键词: Animal Model; Animals; Biology; Biosensor; Cell physiology; Development; Disease; Electromagnetic Fields; Electromagnetics; Etiology; Fatty Acids; Fatty acid glycerol esters; Functional disorder; Glucose; Goals; Human; Insulin Resistance; Maps; Medical Technology; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolic dysfunction; Metabolism; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Nutrient availability; Oxidation-Reduction; Pathway interactions; Pharmaceutical Preparations; Physiological; Planet Earth; Process; Recording of previous events; Signal Transduction; Superoxides; Unconscious State; Work; biological systems; detection of nutrient; diabetic; innovation; interdisciplinary approach; novel; novel strategies; novel therapeutic intervention; programs; response; sensor; transmission process; wireless

Project Summary / Abstract Metabolic dysfunction is a central mechanism in the etiology of numerous metabolic diseases, including type 2 diabetes (T2D). These perturbations are driven by the aberrant redirection of glucose, fatty acid and redox metabolic pathways, favoring fat accumulation and insulin resistance. The development of innovative and targeted strategies to precisely reprogram these pathways would serve as a breakthrough for the treatment of metabolic disease. A long history of work demonstrates that animals across all major phyla possess undiscovered mechanisms that enable biological systems to sense and respond to static electromagnetic fields (EMFs). In humans such mechanisms unconsciously detect changes in the orientation of static EMFs and trigger physiological changes. If these evolutionarily conserved mechanisms could be harnessed, they would lead to the development of automated, targeted and drug-free therapies, which precisely reprogram cellular processes to treat disease. However, a major obstacle is that these mechanisms remain among the least well understood in biology; we understand neither the fundamental mechanisms nor the full range of physiological effects of EMFs. The goal of this proposal is to decipher an undiscovered multicellular network of biological sensors that receive and relay EMF signals. We aim to harness these mechanisms to develop new therapeutic strategies and medical technologies that enable the wireless reprogramming of metabolism. Emerging evidence suggests that endogenous EMF-sensing mechanisms involve short-lived, tightly regulated paramagnetic radicals, such as superoxide. Intriguingly, the paramagnetic radicals which have been proposed to facilitate EMF-sensing in animals, also sense nutrient availability and are implicated in the pathophysiology of type 2 diabetes (T2D). In this proposal, we will leverage our recent serendipitous findings that exposure of diabetic animal models to static EMFs treats T2D in a superoxide-dependent mechanisms to illuminate an undiscovered network of EMF- sensitive sensors and metabolic pathways that may be targeted to wirelessly reprogram metabolism. Our central hypothesis is that weak static EMFs activate an evolutionarily conserved nutrient sensing pathway, representing a novel fundamental unit of biology that relays sub-atomic spin-state signals into systemic metabolic responses. Using state-of-the-art, multidisciplinary approaches to probe the deepest levels of systemic metabolism in healthy and diabetic states, we will decipher a novel endogenous signaling strategy that receives EMF-signals and transmits this information into precise metabolic responses. This work will establish a comprehensive metabolic map of the effects of static EMFs that has the potential to reveal new metabolic pathways, which remain undiscovered in the absence of EMF manipulations. In the process of our work, we will also determine the impact that Earth EMFs have on metabolic pathways. Ultimately, this proposal will pave the way for the development of new approaches which precisely tune metabolic programming, wirelessly.

项目摘要 /摘要 代谢功能障碍是多种代谢疾病的病因中的一种核心机制，包括2型 糖尿病（T2D）。这些扰动是由葡萄糖，脂肪酸和氧化还原的异常重定向驱动的 代谢途径，有利于脂肪积累和胰岛素抵抗。创新和 精确重新编程这些途径的有针对性的策略将成为治疗的突破 代谢疾病。悠久的工作历史表明，所有主要门的动物都拥有 未发现的机制，使生物系统能够感知和响应静态电磁场 （EMFS）。在人类中 生理变化。如果可以利用这些进化保守的机制，它们将导致 自动化，有针对性和无药物疗法的发展，这些疗法精确地重编程了细胞过程 治疗疾病。但是，一个主要的障碍是这些机制仍然是最不理的 生物学我们既不了解基本机制，也不了解 EMFS。该建议的目的是破译未发现的生物传感器的多细胞网络，该网络 接收和继电器EMF信号。我们旨在利用这些机制制定新的治疗策略和 能够无线重编代谢的医学技术。新兴证据表明 内源性电动势感应机制涉及短暂的，紧密调控的顺磁性自由基，例如 超氧化物。有趣的是，已提出的顺磁性自由基促进EMF-Sensing 动物，也感知养分的可用性，并与2型糖尿病（T2D）的病理生理有关。在 这项建议，我们将利用我们最近的偶然发现，即糖尿病动物模型暴露于静态 EMF在超氧化物依赖性机制中处理T2D，以阐明未发现的EMF-网络 敏感的传感器和代谢途径可能针对无线重编代谢。我们的中心 假设是弱静态电动势激活了进化保守的营养感应途径，代表 一种新型的生物学基本单元，将亚原子旋转状态信号传递到系统性代谢反应中。 使用最先进的多学科方法来探测最深的全身代谢水平 健康和糖尿病状态，我们将破译一种新型的内源信号传导策略，该策略接收EMF信号 并将这些信息传输到精确的代谢反应中。这项工作将建立全面 静态EMF的作用的代谢图，有可能揭示新的代谢途径，这些途径 在没有EMF操纵的情况下，仍未发现。在我们的工作过程中，我们还将确定 EMF对代谢途径的影响。最终，该提议将为 开发新方法，这些方法无线地调整了代谢编程的精确调整。