A human receptor screening resource for host-pathogen interactions

病毒、细菌、真菌和寄生虫等传染性病原体在人类中引起疾病，在全世界造成巨大的人道主义负担和巨大的经济成本。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，对于了解感染如何进展以及我们免疫系统的细胞如何反应特别重要。至关重要的是，了解感染初始阶段所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，因为它们具有特殊的生物化学性质;因此，研究这类蛋白质相互作用仍然是一个重要的，但相对而言尚未探索的科学领域。在过去的十年中，我们已经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种不同分子的文库，这些分子代表了人类受体的相关外部区域，这些区域更容易在实验中使用。我们的研究表明，这些蛋白质文库可用于回答许多不同研究领域中的重要生物学问题，但在检测宿主-病原体相互作用方面尤其有用。到目前为止，我们已经编译了一个文库，其中包含了所有已知人类受体的不到一半，这是一个非常有价值的资源，尽管目前还不完整。我们从其他科学家频繁的主动请求中了解到，对这种受体库的访问存在潜在需求;然而，生产这些蛋白质是资源密集型的，因此在临时基础上支持单个项目在经济上变得不可行。为了解决这个问题，我们建议与英国研究中心建立伙伴关系，这些研究中心在致病病毒，细菌，真菌和寄生虫方面具有世界领先的专业知识，以建立一个集中的研究基础设施，以确定宿主-病原体相互作用。为了扩大文库的整体效用，我们将获得缺失的分子，以制作一套全面的人类受体。我们还希望确保该平台成为一个长期的研究基础设施，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，以收费服务模式收回运行成本。如果实现，这些伙伴关系将在英国建立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，学术研究实验室都无法公开获取类似的资源，这意味着这种资源将立即创造出原本不存在的研究机会。我们设想，这种技术平台将促进能够改善人们生活质量的基本发现，包括发现人类病毒受体，从而评估它们造成人类疾病的潜力。并确定开发新疫苗的目标。

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.