The rational design of artificial membrane-binding proteins for advanced cell therapies

用于先进细胞疗法的人工膜结合蛋白的合理设计

• 批准号: 2280398
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2280398
• 关键词: rational; design; artificial; membrane; binding

Cell therapies offer new and unique solutions to a range of maladies. However, cell therapies are limited by their ability to reach their target locations, remain there, and survive within unsuitable environments, such as hypoxia. Augmenting cell therapies towards circumventing these limitations is an exciting area of research which this project intents to address. Through engineering supercharged proteins it is possible conjugate them to surfactants via electrostatic interactions. In doing so, they are able to anchor themselves within the outer membrane of cells. While supercharged Myoglobin (anchor protein) offers the function of oxygen storage, it is also possible to conjugate secondary proteins with added function to the anchor protein to confer additional benefits e.g., homing or signalling. One such 'partner protein' is the programmed cell death protein 1 (PD1) which is a common hindrance for cancer treatments. This project intends to tackle some of the limitations of cell therapies through engineering different assemblies of anchor and partner proteins to be tested in vivo as possible cell therapy add-ons.

细胞疗法为一系列疾病提供了新的独特的解决方案。然而，细胞疗法受限于它们到达目标位置、保持在那里以及在不合适的环境（例如缺氧）中存活的能力。增强细胞疗法以规避这些限制是一个令人兴奋的研究领域，该项目打算解决。通过改造超电荷蛋白质，可以通过静电相互作用将它们与表面活性剂缀合。在这样做的过程中，它们能够将自己锚在细胞的外膜内。虽然超荷肌红蛋白（锚蛋白）提供储氧功能，但也可以将具有附加功能的二级蛋白缀合至锚蛋白以赋予额外的益处，归航或发信号。其中一种“伴侣蛋白”是程序性细胞死亡蛋白1（PD1），它是癌症治疗的常见障碍。该项目旨在通过工程改造不同的锚和伴侣蛋白组装体来解决细胞治疗的一些局限性，这些组装体将作为可能的细胞治疗附加物在体内进行测试。