A human receptor screening resource for host-pathogen interactions

用于宿主与病原体相互作用的人类受体筛选资源

• 批准号: MR/X019705/1
• 负责人: Gavin Wright
• 金额: $ 69.8万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FX019705%2F1
• 关键词: human; receptor; screening; resource; host

Infectious agents such as viruses, bacteria, fungi, and parasites cause disease in humans resulting in an enormous humanitarian burden and huge economic costs throughout the world. Direct interactions between the molecules displayed on the surface of our cells and pathogens are usually the first point of contact during an infection and are particularly important to understand how the infection will progress, and how cells of our immune systems will react. Crucially, understanding the molecules that are involved in the initial stages of infection can provide rational pathways to develop new therapeutic strategies and vaccines. Despite their medical importance, detecting interactions between host and pathogen cell surface molecules is challenging because of their specialised biochemical nature; consequently, studying this class of protein interaction remains an important, but relatively underexplored area of science.Over the last decade, we have developed specialised techniques to investigate these receptors and how they interact with other molecules. At the core of these methods is the creation of libraries containing several hundred different molecules that represent the pertinent external regions of human receptors that are much easier to work with experimentally. Our research has shown that these protein libraries can be used to answer important biological questions in many different fields of research but have been especially useful to detect host-pathogen interactions.So far, we have compiled a library that represents just under half of all the known human receptors representing a very valuable - although currently incomplete - resource. We know from frequent unsolicited requests from other scientists that there is a latent demand for access to this receptor library; however, producing these proteins is resource intensive so that supporting individual projects on an ad hoc basis becomes economically unviable. To address this, we are proposing to establish partnerships with UK research centres with world-leading expertise in pathogenic viruses, bacteria, fungi and parasites to create a centralised research infrastructure to identify host-pathogen interactions. To widen the overall utility of the library, we will obtain the missing molecules to make a comprehensive set of human receptors. We also want to ensure that this platform becomes a long-standing research infrastructure and so an important objective is to transition the platform into a self-sustaining entity that recovers running costs on a fee-for-service model. If realised, these partnerships would create a national research infrastructure in the UK that can be used by scientists from many different areas of biomedical research. Importantly, there are no similar resources that exist in the UK or the rest of the world that are openly accessible to academic research laboratories meaning this resource would immediately create research opportunities that would not otherwise exist.We envisage that this technical platform will facilitate basic discoveries that could improve the quality of peoples' lives including discovering human receptors for viruses and thereby assess their potential to cause future pandemics and identify targets for developing new vaccines.

病毒、细菌、真菌和寄生虫等感染性物质会引起人类疾病，在世界各地造成巨大的人道主义负担和巨大的经济损失。显示在我们细胞表面的分子与病原体之间的直接相互作用通常是感染过程中的第一个接触点，对于了解感染将如何发展以及我们免疫系统的细胞将如何反应尤为重要。至关重要的是，了解感染初期涉及的分子可以为开发新的治疗策略和疫苗提供合理的途径。尽管它们在医学上很重要，但由于它们的特殊生化性质，检测宿主和病原体细胞表面分子之间的相互作用是具有挑战性的；因此，研究这类蛋白质相互作用仍然是一个重要但相对未被探索的科学领域。在过去的十年里，我们开发了专门的技术来研究这些受体以及它们如何与其他分子相互作用。这些方法的核心是创建包含数百个不同分子的文库，这些分子代表人类受体的相关外部区域，更容易在实验中使用。我们的研究表明，这些蛋白质文库可以用来回答许多不同研究领域的重要生物学问题，特别是在检测宿主与病原体的相互作用方面。到目前为止，我们已经编制了一个文库，它代表了所有已知人类受体的不到一半，代表了一个非常有价值的-尽管目前还不完整-资源。我们从其他科学家经常主动提出的请求中了解到，对访问这个受体文库存在潜在的需求；然而，生产这些蛋白质是资源密集型的，因此在特别的基础上支持个别项目在经济上是不可行的。为了解决这一问题，我们提议与英国研究中心建立伙伴关系，在致病病毒、细菌、真菌和寄生虫方面拥有世界领先的专业知识，以创建一个中央研究基础设施，以确定宿主与病原体的相互作用。为了扩大文库的整体用途，我们将获得缺失的分子来制造一套全面的人类受体。我们还希望确保这个平台成为一个长期存在的研究基础设施，因此一个重要的目标是将该平台转变为一个自我维持的实体，以按服务收费的模式收回运营成本。如果实现，这些伙伴关系将在英国创建一个国家研究基础设施，可供来自许多不同生物医学研究领域的科学家使用。重要的是，在英国或世界其他地方，没有学术研究实验室可以公开访问的类似资源，这意味着这些资源将立即创造否则不存在的研究机会。我们预计，这个技术平台将促进基本发现，这些发现可以改善人们的生活质量，包括发现人类病毒受体，从而评估它们导致未来大流行的可能性，并确定开发新疫苗的目标。