Bio-ART: Multiscale understanding of BIOfilms and microBIOmes in Acute Recurrent Tonsillitis.

我们目前对扁桃体炎的基础科学的了解非常差。这个项目的目的是评估扁桃体病变的基本生物学。我们的目标是评估从基因组到实体器官水平的扁桃体病变的复杂性，创建扁桃体-生物膜相互作用的3D体外可扩展模型。这将使用新的科学进步来交付，以允许对患病的扁桃体进行3D建模和绘制地图。复发的扁桃体炎会给患者带来严重的问题，包括喉咙痛和需要多个疗程的抗生素治疗的疼痛。患者患扁桃体炎时，往往不得不抽出时间去托儿所/学校/大学/工作。患者经常反复发作扁桃体炎，需要从他们的全科医生那里获得多个疗程的抗生素。这一切都会对一个人的生活质量造成非常负面的影响。如果患者频繁服用抗生素，这也会引起人们对抗生素耐药性的担忧。最终，如果患者一年有7次或更多的扁桃体炎发作，那么建议进行扁桃体切除术。然而，这并不是一个没有风险的手术，不幸的是，由于疼痛和出血，20%的扁桃体摘除患者不得不在手术后两周内再次入院。这不是一个理想的临床情况，引起了患者的很多关注和担忧。生物膜是一群细菌，在反复发作的扁桃体炎患者中发现了它们。科学家们在扁桃体切除手术中从患者身上取出扁桃体组织后，在显微镜下观察了组织，发现组织中存在细菌集群(生物膜)。生物被膜可以出现在许多不同的感染中，我们知道它们很难用抗生素治疗，甚至可能对抗生素产生抗药性。这可能解释了为什么一些患者尽管从他们的全科医生那里得到了多个疗程的抗生素，但仍然患有扁桃体炎。这是复发性扁桃体炎的一个非常新的研究领域，已经开发了新的科学技术来帮助研究生物膜和抗生素耐药性。这是斯特拉斯克莱德大学研发的一种新型显微镜。建造它的目的是让科学家能够观察大片组织，并看到组织中不同的细胞和细菌。将中胚层用于扁桃体切除患者的扁桃体组织，将使我们能够看到导致扁桃体炎的不同类型的细菌。这样我们就可以更好地了解扁桃体中细菌的复杂性，以及它与感染的关系。这提供了一个非常令人兴奋的机会来使用这种新的和创新的科学设备来帮助理解一个非常常见的临床问题-扁桃体炎。3D生物打印--这是斯特拉斯克莱德大学开发的一项新技术。科学家们开发了一种技术，可以使用通常会在体内引起感染的相同细菌，制作实验室打印的3D感染版本。在这个项目中，我们计划使用导致人类扁桃体炎感染的细菌，并使用3D生物打印来生成实验室制作的扁桃体感染的3D模型。通常在实验室里，我们使用2D实验室制造的感染来测试抗生素和药物。人类的感染是3D的，所以开发扁桃体感染的3D生物打印模型将使我们能够模拟人类的感染，并测试不同的抗生素和药物，看看我们是否能找到治疗扁桃体炎的更好方法。代谢组学--这是了解扁桃体中的分子是如何受到引起扁桃体炎的细菌的影响的。这可以帮助我们理解为什么一些患者对抗生素没有很好的反应。让医生和科学家使用新的创新技术合作，将使我们能够增加对这种非常常见的疾病的了解，并有助于发现新的治疗方法。

Our current understanding of the basic science of tonsillitis is very poor. The aim of this project is to assess the basic biology of the diseased tonsil.We aim to assess the complexity of the diseased human tonsil from the genomic to the solid organ level, creating a 3D in-vitro scalable model of tonsil - biofilm interaction. This will be delivered using new scientific advances to allow 3-D modelling and mapping of the diseased tonsil. Recurrent tonsillitis causes significant problems to patients, including sore throat and pain requiring multiple courses of antibiotics. Patients often have to take time of nursery/school/university/work when they are unwell with tonsillitis. Patients often get recurrent episodes of tonsillitis, requiring multiple courses of antibiotics from their GP. This can all cause a very negative impact on a persons quality of life. It also causes concerns about antibiotic resistance, if the patient is taking frequent courses of antibiotics. Ultimately if the patient gets 7 or more episodes of tonsillitis a year, then tonsillectomy is recommended. However, this is an operation not without risk and unfortunately 20% of patients that get their tonsils out have to be readmitted to hospital within 2 weeks of their operation due to pain and bleeding. This is not an ideal clinical situation and causes patients a lot of concern and worry. Biofilms are clusters of bacteria, and they have been found in patients who get recurrent tonsillitis. Scientists have looked at tonsil tissue under the microscope after it is removed from the patient during tonsillectomy and found that there are clusters of bacteria (biofilms) present in the tissue. Biofilms can occur in lots of different infections and we know that they are difficult to treat with antibiotics and can even be resistant to antibiotics. This may explain why some patients keep getting tonsillitis despite getting multiple courses of antibiotics from their GP. This is a very new area of research for recurrent tonsillitis, and there are new scientific techniques that have been developed to help research biofilms and antibiotic resistance. The Mesolens - this is a new microscope that was developed at Strathclyde University. It was built to allow scientists to look at large pieces of tissue and see the different cells and bacteria in the tissue. Using the Mesolens on tonsil tissue from patients that had their tonsils removed will allow us to see the different types of bacteria that cause tonsilliits. We can then better understand the complexity of the bacteria in the tonsil and how that is relevant to infection. This offers a very exciting opportunity to use this new and innovative scientific equipment to help understand a very common clinical problem - tonsillitis. 3D bioprinting - this is a new technique that was developed at Strathclyde University. The scientists developed a technique to make a lab printed 3D version of infection using the same bacteria that normally cause infections in the body. In this project we plan to use the bacteria that cause tonsillitis infections in humans and use 3D bioprinting to generate a 3D model of a tonsil infection made in the lab. Normally in the lab we use 2D lab made infections to test antibiotics and drugs. Infections in humans are in 3D, so developing a 3D bioprinted model of a tonsil infection will allow us to mimic the infection in humans and test different antibiotics and drugs to see if we can find a better way to treat tonsillitis. Metabolomics - this is understanding how the molecules in the tonsil are affected by the bacteria that cause tonsillitis. This can then help us understand why some patients dont respond well to antibiotics. Having doctors and scientists working together using new innovative techniques will enable us to increase our understanding of this very common disease and help discover new treatments.