INSPIRE: Optogenetic Control of the Human Heart - Turning Light into Force

INSPIRE研究奖由土木、机械和制造创新部门(CMMI)的生物力学和机械生物学(BMMB)和材料力学(MOM)项目以及化学、生物、环境和运输系统(CBET)部门的生物光子学项目共同资助，这两个项目都在工程局(ENG)。仅在美国，每年就有近50万人死于心律失常。尽管电刺激具有侵入性，但它仍然是治疗心脏节律紊乱的黄金标准。这个项目挑战了如何处理人类心脏电信号的传统智慧。长期目标是建立一种新的技术来安全、精确和远程地控制心律失常，只需使用一种名为光遗传学的新概念就可以实现。这项研究的目标是创造一种基因工程细胞的生物起搏器，使我们能够破译光遗传学调节心脏泵功能的基本机制。这一研究方法是对光刺激在四个生物尺度上的系统的理论、实验和计算表征。这项工作具有很高的创新性，因为它首次采用光遗传学来控制人类心脏细胞和组织。它结合了光学、遗传学、干细胞生物学、电生理学、机械生物学、生物力学、数学建模和计算机模拟方面的概念、方法和最新发展。它不同寻常的跨学科性质有可能揭示生命系统的光电化学和力学的基本机制。这一知识的获得将刺激光遗传学的发现，并启动操纵可兴奋细胞的新技术。这项工作的变革潜力在于，它可能开辟新的途径，支持设计各种类型的神经元、肌肉骨骼、胰腺和心脏疾病的治疗方法，如抑郁症、精神分裂症、瘫痪、糖尿病、疼痛综合征和心律失常。

This INSPIRE Research Award is co-funded by the Biomechanics and Mechanobiology (BMMB) and the Mechanics of Materials (MoM) Programs in the Division of Civil, Mechanical, and Manufacturing Innovation (CMMI), and the Biophotonics Program in the Division of Chemical, Biological, Environmental, and Transport Systems (CBET), both in the Directorate for Engineering (ENG). In the United States alone, almost half a million people die each year as a result of heart rhythm disorders. Despite its invasive nature, electrical stimulation remains the gold standard treatment for rhythm disturbances in the heart. This project challenges the conventional wisdom of how to manipulate electrical signals in the human heart. The long-term goal is to establish a novel technology to control heart rhythm disorders, safely, precisely, and remotely, simply by means of light using a new concept known as optogenetics. The objective of this research is to create a biological pacemaker of genetically engineered cells that will allow us to decipher the basic mechanisms by which optogenetics can regulate the pump function of the heart. The research approach is a systematic theoretical, experimental, and computational characterization of photostimulation across four biological scales.This work is highly innovative, since it adopts optogenetics, for the first time, to control human heart cells and tissue. It combines concepts, methods, and recent developments in optics, genetics, stem cell biology, electrophysiology, mechanobiology, biomechanics, mathematical modeling, and computer simulation. Its unusual interdisciplinary nature has the potential to reveal fundamental mechanisms of the photoelectrochemistry and mechanics of living systems. This knowledge gain will stimulate discovery in optogenetics and initiate new technologies to manipulate excitable cells. The transformative potential of the work is that it may open new avenues to support the design of novel therapies for various types of neuronal, musculoskeletal, pancreatic, and cardiac disorders such as depression, schizophrenia, paralysis, diabetes, pain syndromes, and cardiac arrhythmias.