Engineering Surface Topography to Influence Horizontal Gene Transfer in Bacteria.

这个原理验证项目的目的是明确地证明工程表面形貌对设计能够控制HGT的材料和设备的重要性。具体而言，我们建议使用临床相关的肠杆菌科，最近开发的碳青霉烯类抗生素（最后的药物）通过接合质粒的HGT的耐药性菌株，调查表面形貌如何影响HGT。我们将选择抗性供体和非抗性受体菌株，并在使用软光刻技术开发的受控表面形貌的微生境中进行交配实验。在这里，使用光学显微镜，我们将能够监测传输速率（也由于其他因素，例如，空间斑块、流动以及营养物和抗生素在环境中的分布）。除了科学兴趣，该项目将为学生提供宝贵的多学科培训，因为它将使用微生物学，分子生物学，微加工，微流体和先进显微镜的方法的新组合。该项目与几个ESPRC研究主题（工程，医疗保健技术，制造未来）重叠，本质上是基础。事实上，我们提出了一个概念验证的可能性，工程表面形貌的材料和设备，以控制HGT的演示。

The aim of this proof-of-principle project is to unambiguously demonstrate the importance of engineering surface topography to design materials and devices capable of controlling HGT. Specifically, we propose to use strains of clinically relevant Enterobacteriaceae, which have recently developed resistance to the carbapenem antibiotics (drugs of last resort) through HGT of conjugative plasmids, to investigate how surface topography can affect HGT. We will select resistant donor and non-resistant recipient strains and carry out mating experiments in microhabitats of controlled surface topography developed using soft-lithography techniques. Here, using optical microscopy, we will be able to monitor rates of transfer (also due to other factors, e.g., spatial patchiness, flows as well as distribution of nutrients and antibiotics in the environment). Beyond the scientific interest, this project will offer valuable multidisciplinary training to the student as it will use a novel combination of methods from microbiology, molecular biology, microfabrication, microfluidics and advanced microscopy. This project overlaps with several ESPRC Research Themes (Engineering, Healthcare Technologies, Manufacturing the Future) and is foundational in nature. We are in fact proposing a proof-of-concept demonstration of the possibility of engineering surface topography in materials and devices to control HGT.