A microfluidic system and confocal microscope for the molecular and mechanistic characterisation of microbial biofilms

微生物，如细菌和真菌，是在地球上的广泛环境中以及人类和动物体内发现的微小生物体。它们既有积极的影响，也有消极的影响;然而，我们更经常地意识到它们的存在与它们对健康（例如传染病）和工业（例如金属腐蚀）的负面影响有关。生物膜是微生物生长的主要模式，由一个由自我产生的分子组成的防御网（生物膜基质）粘在一起的细胞团块组成。这种形式的生长提供了保护，免受外部因素，如脱水，但也免受其他生物体，宿主免疫系统和抗菌化合物的攻击。生物膜的形成在许多工业环境中引起问题，例如在工业水系统、航运、农业以及医疗和加工工业中。据估计，全球经济成本超过4万亿美元，英国超过1000亿英镑。生物膜的生长也对抗菌素耐药性的出现产生了重大影响，这是目前对人类的最大威胁之一。它们是复发性疾病的主要原因，它们对严重感染的建立起重要作用，并且它们每年花费英国国家卫生服务（NHS）超过20亿英镑进行治疗。我们寻求获得一个微流控系统和一个专门的（共聚焦）显微镜，这将使国王的深入研究如何生物膜的形成和如何消除它们。这种表征到单个细胞的大小尺度对于这些生物过程的基本理解以及新药开发至关重要。特别是，我们将在研究工作中广泛使用该设备，以了解口腔和炎症性疾病（例如蛀牙，牙龈疾病，鹅口疮，炎症性肠病，克罗恩病）的进展，并开发治疗这些疾病以及肺部，指甲，伤口和医院获得性感染的新方法。这些类型的研究也有可能导致识别出可开发成新生物材料的分子，以及可用于解决工业环境中生物膜的方法。该仪器将使我们不仅能够发展我们在国王学院现有的研究，而且还将有助于开发新的研究途径，并培养下一代生物分子科学家。此外，我们寻求购买的仪器的一个特别优势是，它不仅允许我们在连接到显微镜时研究活体生物膜，而且还可以将其移除，以便使用其他设备研究更精细的细节，这些设备也可以在国王和国家设施中使用。这将使我们能够跨越尺度，从分子到细胞，建立我们的研究，并在国王的生物膜研究中心。

Microbes, such as bacteria and fungi, are tiny organisms found in a wide range of environments on the earth, and within humans and animals. They have both positive and negative impacts; however, we are more often aware of their existence in relation to their negative effects such as on health (e.g. infectious disease) and in industry (e.g. corrosion of metals). Biofilms are the principal mode of microbial growth and consist of a clumping of cells glued together by a defensive mesh of self-produced molecules (the biofilm matrix). This form of growth provides protection from external factors such as dehydration but also from attack by other organisms, the host immune system and antimicrobial compounds. Biofilm formation causes problems in many industrial settings, such as in industrial water systems, shipping, agriculture, and the medical and process industries. This has an estimated economic cost of >$4tn globally and >£100bn in the UK. Biofilm growth has also had a major influence on the emergence of antimicrobial resistance, which currently represents one of the largest threats to humankind. They are a major cause of recurrent disease, they contribute significantly to the establishment of serious infections, and they cost the UK National Health Service (NHS) >£2bn to treat each year. We seek to acquire a microfluidic system and a specialised (confocal) microscope, which will allow King's to study in great depth how biofilms form and how they can be eradicated. This characterisation down to the size scale of individual cells is critical for the fundamental understanding of these biological processes, as well as for new drug development. In particular, we will use this equipment extensively in our research efforts to understand the progression of oral and inflammatory diseases (e.g. tooth decay, gum disease, thrush, inflammatory bowel disease, Crohn's disease), and develop new ways of treating these diseases, as well as lung, nail, wound and hospital acquired infections. It is also possible that these types of study will result in the identification of molecules that can be developed into new biomaterials, and approaches that can be used to tackle biofilms in industrial settings. This instrument will permit us not only to develop our existing research at King's but will also be instrumental to develop new avenues of research, and for the training of the next generation of biomolecular scientists. In addition, a particular advantage of the instrument we seek to purchase, is that it allows us to not only study living biofilms while attached to the microscope, but they can also be removed so that even finer details can be investigated using other equipment which is also accessible within King's and at national facilities. This will enable us to bridge our studies across scales, from molecules to cells, and create a hub for biofilm research at King's.