Rotation 1: Microelectrode arrays for astrocyte electrophysiology

第 1 轮：用于星形胶质细胞电生理学的微电极阵列

• 批准号: 2887961
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2887961
• 关键词: Rotation; Microelectrode; arrays; astrocyte; electrophysiology

BBSRC strategic theme: Transformative technologiesCommunication, defined as the exchange of information between entities, plays an essential role not only at the societal but also cellular level, facilitating the progression of complexity and intelligence. As physiological functions and mechanisms become increasingly sophisticated, scientists encounter greater challenges in comprehensively investigating and understanding them. In vitro models offer a means to alleviate this complexity by faithfully replicating relevant in vivo characteristics while striking a balance between simplicity and accuracy, thereby enhancing biological relevance and statistical robustness of experimental outcomes. However, the utility of these models is constrained by the tools available for communicating with these models, i.e. investigation and interaction techniques. Given the distinct languages spoken by humans and cells, a bidirectional interface, akin to a language translator, is essential to enable the exchange of information between cells and humans. Bioelectronics has emerged as a promising avenue for constructing such bidirectional interfaces, enabling continuous, label-free monitoring and precise control of biological activity. By translating chemical and electrical signals, both pivotal players in cellular communication, bioelectronics facilitates a deeper understanding of and better control over cellular processes. Unlike conventional in vitro systems, which are often assessed through infrequent measurements and manual interventions, system integration of bidirectional interfaces opens new avenues for developing sophisticated tools that provide deeper insights into biological systems. Moreover, combining bioelectronics with biomimetic approaches leverages nature's solutions such as membrane receptors for signal transduction utilised in bioelectronic sensing with biomembranes or electrical cell stimulation, thereby bridging the formidable capabilities of biology and electronics. The primary objective of this project is the system integration of bidirectional biomimetic interfaces in regulatory pathway models to explore human physiology in vitro. While developing a platform that can be tailored to various physiological pathways by leveraging the advantages of biomimetic bioelectronic approaches for interfacing with biological structures presents the ultimate goal, demonstration of its capabilities will be achieved by initially focusing on one specific systemic pathway of human physiology. The gut-brain axis presents an intriguing candidate for such a system, given its widespread connections throughout the body and indications of influence on information processing, which recently received a great deal of attention. With electrical and chemical signals exchanged across bodily distances, this system offers a fittingly complex model. Specifically, the serotonin pathway, characterised by its profound systemic effects, poses challenges for isolated investigation in animal models. Developing a platform that mimics relevant features of this pathway would provide valuable insights in the complex interplay between gut and brain.Thus, relevant cell lines involved in the serotonin pathway should be co-cultured within a microphysiological system to model a facet of the gut-brain axis in vitro. Concurrently, a bidirectional biomimetic interface, incorporating bioelectronic elements such as biomembrane sensors and electrical cell stimulation, should be seamlessly integrated to enable continuous monitoring and precise modulation of systemic behaviour. A platform as the one proposed here holds promise for advancing our understanding of and communication capabilities with living systems, which facilitates subsequent interventions and leverages technology to enhance knowledge and human well-being.

BBSRC战略主题：通信被定义为实体之间的信息交换，不仅在社会层面而且在细胞层面都发挥着至关重要的作用，促进了复杂性和智能的发展。随着生理功能和机制的日益复杂，科学家在全面研究和理解它们时遇到了更大的挑战。体外模型通过忠实地复制相关的体内特征，同时在简单性和准确性之间取得平衡，从而增强实验结果的生物相关性和统计稳健性，从而提供了一种减轻这种复杂性的方法。然而，这些模型的实用性受到与这些模型进行通信的工具的限制，即调查和互动技术。鉴于人类和细胞使用不同的语言，一个类似于语言翻译器的双向接口对于实现细胞和人类之间的信息交换至关重要。生物电子学已经成为构建这种双向接口的一个有前途的途径，可以实现对生物活性的连续、无标记监测和精确控制。通过翻译细胞通信中的关键参与者化学和电信号，生物电子学促进了对细胞过程的更深入理解和更好控制。与通常通过不频繁的测量和手动干预进行评估的传统体外系统不同，双向接口的系统集成为开发提供更深入了解生物系统的复杂工具开辟了新的途径。此外，将生物电子学与仿生方法相结合，利用了自然界的解决方案，例如用于生物电子传感的信号转导的膜受体，生物膜或电细胞刺激，从而桥接了生物学和电子学的强大功能。本计画的主要目的是系统整合双向仿生介面于调控路径模型中，以探讨人体体外生理学。虽然开发一个平台，可以通过利用仿生生物电子方法的优势，与生物结构接口的各种生理途径量身定制的最终目标，其能力的演示将通过最初专注于一个特定的人体生理系统途径实现。肠-脑轴是这种系统的一个有趣的候选者，因为它在整个身体中的广泛联系以及对信息处理的影响，最近受到了极大的关注。由于电子和化学信号在身体距离上交换，这个系统提供了一个非常复杂的模型。具体而言，5-羟色胺途径，其特点是其深刻的全身效应，提出了挑战，在动物模型中的孤立调查。开发一个模拟该途径相关特征的平台将为肠道和大脑之间复杂的相互作用提供有价值的见解。因此，参与5-羟色胺途径的相关细胞系应在微生理系统中共培养，以模拟体外肠-脑轴的一个方面。同时，一个双向仿生接口，结合生物电子元件，如生物膜传感器和电细胞刺激，应无缝集成，以实现连续监测和系统行为的精确调节。这里提出的平台有望促进我们对生命系统的理解和沟通能力，这有助于随后的干预措施，并利用技术来增强知识和人类福祉。