Tackling antibiotic resistance by combining synthetic biology and nanotechnology: development of new biosensing systems

该项目提供了一个连接合成生物学和纳米技术领域的机会，以解决最重要的研究领域之一：日益严重的抗微生物药物耐药性（AMR）问题。细菌对抗生素的耐药性是现代医疗保健中最重大的危机之一。最广泛使用的一类抗生素（以及一般的治疗药物）是β -内酰胺类，包括氨苄西林、阿莫西林和甲氧西林。到目前为止，细菌产生β -内酰胺耐药性的主要机制是产生β -内酰胺酶（BLs），使抗生素失活，从而消除其治疗价值。现代抗菌素治疗的差距是基于检测关键抗菌素耐药性标记物的存在来改善抗生素使用的伴随诊断。通过将合成生物学与纳米技术相结合，生成一种新的检测系统，您的研究将为填补这一空白迈出至关重要的一步。您将把对环境敏感的电子材料与AMR蛋白的独特分子特征联系起来。为了实现这一目标，您将设计一种名为BLIP的蛋白质，它可以与各种各样的BLs结合，以便它可以精确地与基础传感材料碳纳米管（CNTs）结合。碳纳米管是非常有用的传感材料，因为它们的电导率非常敏感，并且会随着局部环境变化（如蛋白质-蛋白质相互作用）而变化。

The project provides an opportunity to bridge the areas of synthetic biology and nanotechnology to address one of the most important areas of research: the growing problem of antimicrobial resistance (AMR). Bacterial resistance to antibiotics is one of the most significant crises in modern healthcare. The most widely utilised class of antibiotics (and therapeutics in general) are the beta-lactams, which include ampicillin, amoxicillin and methicillin. By far the main mechanism bacteria use to confer beta-lactam resistance is the production of beta-lactamases (BLs) that inactivate the antibiotic and thus removing its therapeutic value. A gap in modern antimicrobial treatment is a companion diagnostic for improving antibiotic use based on detecting the presence of key AMR markers. Your studentship will take a vital step towards filling this gap by combining synthetic biology with nanotechnology to generate a new detection system. You will link environmentally sensitive electronic materials to the unique molecular signatures of AMR proteins. To achieve this you will engineer a protein called BLIP that binds to a wide variety of BLs so that it can interface precisely with the base sensing material, carbon nanotubes (CNTs). CNTs are incredibly useful sensing materials as their electrical conductance is highly sensitive and changes in response to local changes in environment such as protein-protein interactions.