Building microbial cities: engineering mucosal biofilm nurseries for Antimicrobial Resistant (AMR) research

生物膜（形成表面菌落的微生物种群）排列在所有哺乳动物的粘膜表面;它们可以窝藏抗菌素耐药病原体，并且是菌落内抗菌素耐药基因交换的温床。它们对我们健康的影响才刚刚意识到，但我们用于研究此类系统的体外模型过于简单，不能反映人类生理学。这限制了我们对生物膜的基本理解和我们识别有效治疗方法（例如联合疗法或新抗生素）的能力;世卫组织表示抗生素耐药性是“当今全球健康，粮食安全和发展的最大威胁之一”。“这项工作的潜在影响是巨大的。作为一项颠覆性技术，它支持对AMR的理解和对现代医学最大威胁的革命性治疗方法的开发对齐：EPSRC医疗技术（i）开发新疗法作为工程平台，允许研究抗菌素耐药生物膜的基础科学和药物治疗的影响;（ii）优化疾病预测，诊断和干预。在国际上，它符合联合国可持续发展目标3的良好健康和福祉（通过支持更快地提供具有成本效益的药物治疗来实现全民健康覆盖）。 目的：新型生物膜“苗圃”模型的工程设计，具有在生理相关条件下操作的先验定义和控制的流体环境。 目的：（a）设计复制体内粘膜生理特征（例如，流量、温度、表面化学）（B）表征生物膜结构和微生物组成，（c）证明模型对设计用于减少肠道环境中AMR病原体的微生物治疗剂的性能。

Biofilms (microbial populations forming surface colonies) line all mammalian mucosal surfaces; they can harbour antimicrobial resistant pathogens and are a hotbed for the exchange of antimicrobial resistance genes within the colonies. Their influence on our health is only just being realised yet the in-vitro models we have for studying such systems are simplistic and does not reflect human physiology. This limits our fundamental understanding of biofilms and our ability (for example) to identify effective treatments such as combination therapies or new antibiotics; the WHO stated antibiotic resistance is "one of the biggest threats to global health, food security, and development today." Potential Impact of this work is significant. As a disruptive technology it supports the understanding of AMR and the development of revolutionary treatments for what is recognised the biggest threat to modern medicine Alignment: to EPSRC Healthcare Technologies (i) Developing new therapies as an engineered platform allows the fundamental science of antimicrobial resistant biofilms and the impact of drug treatments to be studied; (ii)Optimising Disease Prediction, Diagnosis and Intervention. Internationally, it aligns with UN sustainable development goal 3 of good health & well-being (universal health coverage by supporting more rapid delivery of cost-effective drug treatments). Aim: The engineering of novel biofilm 'nursery' models with a-priori defined and controlled fluidic environments operating under physiologically relevant conditions. Objectives: (a) Design biofilm nurseries that replicate in vivo mucosal physiological characteristics (e.g., flow, temperature, surface chemistry) (b) Characterise biofilm structure and microbial compositions, (c) Demonstrate the model performance against microbial therapeutics designed to reduce AMR pathogens in the intestinal environment.