CATSIG: Synthesis and study of catalytic signalling systems to create vesicles that mimic cell sensing and signalling

CATSIG：催化信号系统的合成和研究，以创建模拟细胞传感和信号传导的囊泡

• 批准号: EP/X02122X/1
• 负责人: Nicholas Williams
• 金额: $ 24.26万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX02122X%2F1
• 关键词: CATSIG; Synthesis; study; catalytic; signalling

A critical feature of complex biological systems is the compartmentalisation provided by lipid bilayer membranes. This separates the inside and outside solutions and allows otherwise incompatible chemical processes and networks on the interior and exterior to co- exist independently. However, it is critical that extracellular molecules, such as hormones, nutrients and pathogens, can change the intracellular chemistry - and this is achieved by signalling across the cell membrane, usually via membrane-spanning proteins, which trigger a cascade of reactions which both amplify and transduce the original signal so that the cell can respond appropriately. Vesicles are simplified analogues of cells, and have the potential to store, amplify, transduce and communicate information in the same way, and this proposal aims to functionally mimic the cellular response with entirely synthetic systems. The aim is to couple an external molecular recognition event with an internal catalytic process using a novel transmembrane signal transduction pathway. Vesicles are already used in drug-delivery applications, but there is huge potential for responsive vesicles - those that can react in a specific and targeted way to an external signal such as a molecular binding event - which could be used in targeted drug delivery, such as the catalytic activation of a pro-drug for controlled-release applications. Furthermore, multivalent vesicles that are capable of efficient transduction of chemical information will provide a platform for the construction of biocompatible interfaces for communication with cellular systems for sophisticated sensing applications and diagnostics.

复杂生物系统的一个关键特征是由脂质双层膜提供的区室化。这将内部和外部的解决方案分开，并允许内部和外部的不相容的化学过程和网络独立共存。然而，至关重要的是，细胞外分子，如激素，营养物质和病原体，可以改变细胞内的化学物质-这是通过跨细胞膜的信号传导来实现的，通常通过跨膜蛋白，这会触发一系列反应，这些反应既放大又放大原始信号，以便细胞可以做出适当的反应。囊泡是细胞的简化类似物，并且具有以相同方式存储、放大、储存和传递信息的潜力，并且该提议旨在用完全合成的系统在功能上模拟细胞反应。其目的是耦合一个外部的分子识别事件与内部的催化过程，使用一种新的跨膜信号转导途径。囊泡已经用于药物递送应用，但响应性囊泡具有巨大的潜力-那些可以以特定和靶向方式对外部信号（如分子结合事件）反应的囊泡-可用于靶向药物递送，如用于控释应用的前药的催化活化。此外，能够有效转导化学信息的多价囊泡将提供用于构建生物相容性界面的平台，所述生物相容性界面用于与细胞系统通信以用于复杂的传感应用和诊断。