Optical control of a biological excitable medium

该计划旨在开发新的工具，用于可视化可兴奋的心脏细胞网络中的活动，以获得对其行为的理论见解。中心的科学目标是理解内在的空间分布的非均质性如何影响波的稳定性和向复杂动力学的转变。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，这只在相对简单的光敏化学系统中才可能实现。由于心脏细胞网络是一类更广泛的称为可兴奋介质的物理系统的一部分，研究成果可用于了解不同系统中的模式形成和动力学，如可兴奋的化学反应、黏液霉菌菌落和神经准备。*培养的心脏单层制剂具有内在的异质性，影响了实验的重复性。当驱动具有空间和时间变化的光学输入的异质组织时，实验的重复性问题可能会加剧。在处理这些制剂时，需要新的方法来显著提高实验吞吐量。该计划的目标之一是开发以高通量方式测量多种制剂的活性的方法，以及使用光遗传工具激发多种制剂的方法。建立了一种新型的多井成像系统，该系统基于对经典反射望远镜设计的反转。该系统将适用于在孵化器中对几种准备材料进行连续监测和刺激，这将被用来研究随机的固有空间不均一性如何影响波的稳定性。由于该系统既可以光学记录和刺激多种准备，它最终可能成为将远程实验概念应用于生命科学的试验台(不同地点的研究人员可以在相同的实验准备上工作，提高可获得性、重复性和透明度)。参与该项目的学生将成为一个多学科环境的一部分，该环境提供构建生物工程心表、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方面的培训。该实验室专注于仪器设备的开发，带来了知识产权和许可机会，以及接触工业的机会。该方案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.