Body-on-a-chip: a novel approach to understanding antimicrobial resistance

这个博士项目将是我们努力开发一个全新的，尖端的“芯片上的身体”基于微流体的类器官平台的核心，并将其部署在人类细胞微环境中研究AMR和宿主/病原体相互作用。由于UTI起源于肠道，并从那里上升到膀胱和肾脏，我们将利用我们在人类细胞平台方面的专业知识，将肠道，膀胱和肾脏类器官连接到一个无缝系统中，以研究生态位对感染，生物膜形成和药物敏感性的影响。初步结果表明，细菌对周围环境非常敏感，能够灵活地修改其基因表达模式以适应不同的生态位并逃避抗生素，即使根据标准诊断测试它们是“敏感的”。在该项目的后期，我们希望通过探索皮肤类器官中的伤口感染来扩大研究范围。作为基础科学和转化科学的令人满意的融合，该项目具有巨大的范围，可以揭开关键的生物学奥秘，并帮助测试和完善治疗解决方案，从而在未来为患者带来真实的改变。技术包括组织工程、微流体、微加工、细胞生物学、高分辨率固定和活体成像、微生物学和基因组学。

This PhD project will be at the heart of our efforts to develop an entirely novel, cutting-edge "body-on-a-chip" microfluidic-based organoid platform and to deploy it to study AMR and host/pathogen interactions in a human cell micro-environment. As UTI originates in the gut and from there ascends to the bladder and kidney, we will build on our expertise in human-cell platforms to link gut, bladder and kidney organoids into a seamless system to study the effects of niche on infection, biofilm formation and drug sensitivity. Pilot results suggest that bacteria are exquisitely sensitive to their surroundings, with the ability to flexibly modify their gene expression patterns to adapt to different niches and to evade antibiotics, even when they are "sensitive" according to standard diagnostic tests. Later in the project we expect to expand the reach by exploring wound infection in skin organoids. As a satisfying blend of basic and translational science, this project has massive scope for unveiling key biological mysteries as well as helping to test and perfect therapeutic solutions that can make a real difference to patients in the future. Techniques include tissue engineering, microfluidics, microfabrication, cell biology, high resolution fixed and live imaging, microbiology and genomics.