Optical control of a biological excitable medium

该计划旨在开发新的工具，用于可视化可兴奋心脏细胞网络中的活动，以获得对其行为的理论见解。 中心科学目标是了解内在空间分布的不均匀性如何影响波的稳定性和过渡到复杂的动力学。该计划利用心脏光遗传学领域的最新进展来调整波前速度作为实验参数，直到最近才在相对简单的光敏化学系统中实现。由于心脏细胞网络是称为可兴奋介质的更广泛的物理系统的一部分，因此研究成果可以应用于理解不同系统中的模式形成和动力学，例如可兴奋的化学反应，黏菌菌落和神经准备。培养的心脏单层制备物具有影响实验重现性的内在异质性。 当用空间和时间变化的光学输入驱动异质组织时，实验再现性问题可能会加剧。在处理这些制剂时，需要新的方法来显著提高实验通量。该计划的目标之一是开发以高通量方式测量多种制剂活性的方法，以及使用光遗传学工具激发多种制剂的方法。在对传统反射式望远镜进行反求设计的基础上，建立了一种新型的多阱成像系统。该系统将适于在培养箱中的几种制剂中进行连续监测和刺激，这将被用来研究随机固有空间不均匀性如何影响波的稳定性。由于该系统可以记录和模拟多种制剂的光学，它最终可能是应用远程实验概念的试验台（不同地点的研究人员可以进行相同的实验准备，提高了可访问性，（再现性和透明度）生命科学。参与该计划的学生将成为多学科环境的一部分，该环境提供生物工程心脏片构建方面的培训，高速成像技术，生物光子学，计算机模拟开发以及TB图像数据集的数据分析。 该实验室专注于仪器开发，从而带来了知识产权和许可机会，以及对行业的接触。该计划提供的培训环境使受训者具备学术和私营部门所需的技能。

This program aims to develop new tools for visualizing activity in excitable cardiac cell networks to gain theoretical insights on their behavior. The central scientific goal is to understand the how intrinsic spatially distributed heterogeneities impact wave stability and transitions to complex dynamics. The program leverages recent advances in the field of cardiac optogenetics to tune wave-front velocity as an experimental parameter, which until recently was only possible in relatively simple light sensitive chemical systems. As cardiac cell networks are part of a broader class of physical systems termed excitable media, research outputs can be applied to understanding pattern formation and dynamics in diverse systems, such excitable chemical reactions, slime mold colonies, and neural preparations. Cultured cardiac monolayer preparations have intrinsic heterogeneities that impact experiment reproducibility. Experimental reproducibility issues are likely to be exacerbated when driving heterogeneous tissue with spatially and temporally varying optical inputs. New methods are needed to dramatically improve experimental throughput when working with these preparations. One of the aims of this program is to develop methods for measuring activity from multiple preparations in a high-throughput manner, as well as methods for exciting multiple preparations using optogenetic tools. A novel multi-well imaging system, based on inverting the design of a classical reflecting telescope, has been built as a prototype. This system will be adapted to enable continuous monitoring and stimulation in several preparations in an incubator, which will be leveraged to study how random intrinsic spatial heterogeneities impact wave stability. Since the system can both record and stimulate multiple preparations optically, it may ultimately be test-bed for applying remote experimentation concepts (where researchers in different locations can work on the same experimental preparation, improving accessibility, reproducibility and transparency) to the life sciences.Students involved in this program will be part of a multidisciplinary environment that provides training in construction of bioengineered cardiac sheets, high speed imaging techniques, biophotonics, computer simulation development as well as data analysis of terabyte image data sets. The lab's focus on instrumentation development leads to intellectual property and licensing opportunities, as well as exposure to industry. The training environment provided by this program equips trainees with the skills needed for both the academic and private sectors.