Optical control of a biological excitable medium

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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.