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

Lead Research Organisation: University of Strathclyde
Department Name: Physics


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.

Technical Summary

We have brought together a multidisciplinary team from the University of Strathclyde in partnership with Dr Catriona Douglas, to address important clinical and scientific questions that will allow us to progress towards a better understanding of this clinical problem. The aims of the study are to focus on the evaluation and quantification of infection in the tonsils, imaging characterisation of tonsil biofilms and to develop the first 3D in-vitro model of a tonsil biofilm. Evaluation and quantification of infection will be done using metabolomics and metgenomics. Imaging characterisation will be done using the Mesolens, a new imaging technology developed by Prof McConnell at Strathclyde University department of Physics and named by Physics World as one of the 'Top Ten Breakthroughs in Physics, 2016'. The Mesolens is a large objective lens with a low magnification capable of imaging a large field of view in either wide field epi-fluoresence or laser scanning confocal modes. As a result, the Mesolens allows for imaging a relatively large sample of tissue with sub-cellular resolution with no change in objective magnification, offering a novel imaging method for studying large microbial populations such as biofilms in tonsil tissue. Development of the first 3D in-vitro tonsil biofilm model will use a technique first described by Professor Shu- 3D bioprinting of a mature bacterial biofilm. 3D bioprinting has developed as a technique for depositing living cells and biomaterials to build complex tissue constructs. 3D bioprinting bacterial biofilms has several benefits, the embedded bacteria have been shown to have increased metabolic activity, antimicrobial resistance and plasmid stability in comparison to traditional 2D models, therefore the 3D biofilm potentially mirrors in vivo bacterial growth more closely than 2D models.


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