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

用于微生物生物膜分子和机械表征的微流体系统和共焦显微镜

• 批准号: BB/X019101/1
• 负责人: James Garnett
• 金额: $ 55.27万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX019101%2F1
• 关键词: microfluidic; system; confocal; microscope; molecular

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.

微生物，如细菌和真菌，是在地球上广泛的环境中以及在人类和动物体内发现的微小有机体。它们既有积极的影响，也有消极的影响；然而，我们更多地意识到它们的存在与其对健康(例如传染病)和工业(例如金属的腐蚀)的消极影响有关。生物膜是微生物生长的主要模式，由由自身产生的分子(生物膜基质)组成的防御性网状物粘合在一起的细胞组成。这种生长形式提供了对外部因素的保护，如脱水，但也防止了其他生物、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都会造成问题，例如在工业用水系统、航运、农业以及医疗和加工行业。据估计，这将给全球带来4万亿英镑的经济成本，对英国造成1000亿英镑的损失。生物膜的生长也对抗菌素耐药性的出现产生了重大影响，抗菌素耐药性目前是人类面临的最大威胁之一。它们是复发疾病的主要原因，它们极大地促进了严重感染的建立，每年花费英国国家医疗服务体系(NHS)和GT；GB 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(共焦)显微镜，这将使King‘s能够深入研究生物膜是如何形成的，以及如何根除它们。这种对单个细胞大小的描述对于从根本上理解这些生物过程以及新药开发都是至关重要的。特别是，我们将在研究工作中广泛使用这种设备，以了解口腔和炎症性疾病(如龋齿、牙周病、鹅口疮、炎症性肠道疾病、克罗恩病)的进展，并开发治疗这些疾病以及肺、指甲、伤口和医院获得性感染的新方法。这些类型的研究也可能导致识别可被开发成新的生物材料的分子，以及可用于处理工业环境中的生物膜的方法。这台仪器将使我们不仅能够发展我们在King‘s的现有研究，而且还将有助于开发新的研究途径，并用于培训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的情况下研究活的生物膜，而且还可以将它们移除，以便可以使用其他设备来研究更精细的细节，这些设备也可以在King‘s内部和国家设施中使用。这将使我们能够将我们的研究跨越从分子到细胞的范围，并在King‘s创建一个生物膜研究的中心。