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Team:Dundee/policypractice/experts
From 2014.igem.org
Welcome to Dundee's 2014 Wiki (Site Information)
Cystic Fibrosis is a genetic disease that results in the accumulation of thick mucus in the epithelial linings of the entire body, particularly the respiratory tract. Over the course of a patient’s life, the mucus-lined lung epithelium becomes repeatedly infected with pathogenic bacteria that stimulate an immune response; leading to inflammation, tissue damage, and ultimately, respiratory failure.
The microflora of the Cystic Fibrosis lung changes over time. In childhood, the major coloniser is Staphylococcus aureus, but as the patient matures other bacterial pathogens infect. The later-dominating pathogens, Pseudomonas aeruginosa and Burkholderia cepacia, are very difficult to eradicate and are associated with chronic decline in lung function. Burkholderia is so infectious that patients have to be isolated from one another, and can be denied lung transplants due to the persistence of this bacterium.
It is important, therefore, for medics to monitor and identify the levels of bacteria within the respiratory tract of a Cystic Fibrosis patient. Currently, patients must provide sputum samples and identification of bacteria takes between 72 hours and 2 weeks, by which point the bacteria can be in an antibiotic resistant state.
The Dundee 2014 iGEM project is focused on designing and testing a device that will rapidly and non-invasively identify the bacteria colonising a Cystic Fibrosis patient. Three biosensors will be developed that recognise external signal molecules produced by key bacteria, all of which are known to be in sputum samples of Cystic Fibrosis patients. A quinolone signal (PQS) is produced by Pseudomonas aeruginosa, a Diffusible Signal Factor (DSF) is produced by Stenotrophomonas maltophilia, an organism that is also associated with Cystic Fibrosis lung infection in adults, and BDSF is a related, but chemically distinct molecule that is produced by Burkholderia cepacia.
By engineering signal recognition and signal transduction proteins from these biological systems the Dundee iGEM team want to produce a portable electronic device that will identify infection outside of the clinic, so that patients do not have to travel great distances, and can be used to help health professionals make informed and rapid decisions on antibiotic treatments.
Read this again by clicking on Site Information in the navigation bar!
Bulletin Board (Policy & Practice)
Come look at the poster explaining how we involved the local and national cystic fibrosis community in our project, how we listened to people on the front line of the disease and how they affected our project.
School (Project)
Come in and learn about all the parts that make The Lung Ranger. The lab work that we carried out over the summer is explained here in detail, along with the modelling and implementation.
Library (Log Book)
Read about the experience the team has had over the summer. A week by week description of our work, how we carried out that work and some photos of our time together.
Saloon (iGEM community)
Come on in, take a seat and learn how we have interacted with the larger iGEM community. Who the team are, who helped them and how we helped others.
College of Life Sciences
With more than 1100 staff and research students and external funding of around £60 million per year, the College of Life Sciences is one of the largest and most productive research institutes in Europe. This reputation is genuinely global and is reflected in the fact that researchers in our laboratories represent no fewer than 62 different nationalities
Division of Mathematics A small friendly Division which offers a lively and modern programme of study at both undergraduate and postgraduate level.We have research groups in Mathematical Biology, Numerical Analysis and Scientific Computing, Magnetohydrodynamics and Applied Analysis.
School of Computing With research areas in Human Centred Computing, Intelligent Systems, Space Technologies and Theory of Computation, the department has an emphasis on development. Furthermore, this department teaches popular undergraduate programs in Applied Computing and Computing Science.
We are a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
Policy and Practice
From Bedside to Bench and Back Again
Overview
From the very beginning we have engaged the experts who have a deep understanding of Cystic Fibrosis in order to ensure that our project is addressing a genuine need as defined by those who know best.
Who are these experts? They are the patients, doctors and nurses who deal with this disease every single day. This also meant that patients were acutely aware of the limitations of the project, which we believe reduces the chance of giving false hope to people with a very serious condition. As you look through this policy and practices section you will meet some of these honorary team members. In addition, by presenting The Lung Ranger at the national UK CF trust conference we have explained to a wide audience of funding agencies, clinicians and researchers that synthetic biology is a powerful new tool to help with long standing problems in the management of this devastating disease.
This culminated in an appearance on Scottish Television (STV) News where we could reach an even wider audience with our synthetic biology project. All of these activities were crucial in informing the design of our product, the L.A.S.S.O.. We interacted with our experts regularly throughout the duration of our project taking The Lung Ranger from the bedside to the bench and back again. After all, communication isn’t just important for bacteria in polybacterial infections!
Successful implementation of the Lung Ranger and the L.A.S.S.O. could provide quantifiable benefits to the CF community, the National Health Service and the 'UK PLC'. These themes are explored here.
A Wiki Page for Everyone… Not Only the iGEM Community
In gratitude for the generous contributions of our friends at Ninewells Hospital, Dundee, we thought it was a fitting tribute to design our Wiki page with them firmly in mind. We feel that the artistic design of our Wiki, (our thanks go to Avril, iGEM Alumna), targets a different audience. If those affected by CF and the wider public can learn about the potential of synthetic biology to improve lives, here on our Wiki page, then we believe they are more likely to engage in discussions about how to ensure the technology is used responsibly. Going into the future this is essential in maintaining the integrity of the field.
We had Fun Raising Money for CF Charities
It’s not all serious. We raised money for the Cystic Fibrosis Trust charity by having a bake sale, (the cakes were delicious!) and raising sponsorship money by taking part in a 10K and Half Marathon run. Roddy’s knees no longer function as joints BUT he did work off the cakes. Take a look at some pictures from these events here.
Cystic Fibrosis Trust Conference
News of The Lung Ranger spread quickly in the local community, and we were thrilled to be invited to present at the UK Cystic Fibrosis Conference in Manchester. This national conference saw leading experts in Cystic Fibrosis research, clinicians, and funding agencies gather to discuss novel treatments and national concerns relating to CF.
Gillian and Jenny from the team highlighted the use of Synthetic Biology as a novel, viable and powerful option for CF management and care. Our project had also addressed key points highlighted by directors and researchers of the CF Trust, including; managing digital data, personalizing care and ‘Putting the patient voice at the heart of CF care’ (Oli Raynor, Special Adviser, Research & Patient Involvement at Cystic Fibrosis Trust).
It was clear from the feedback that we were attempting to address an unmet clinical need, and this was further evidenced when we received messages on social media from people watching online.
Clinic Visits
From the offset we visited our local CF clinic in Ninewells Hospital, Dundee, as well as making visits to Western General in Edinburgh. Patients were extremely generous with their time, sharing what it was like living with CF, the biggest day to day challenges they faced and what could help them reduce the burden of care they experienced. This information was vital to our project, and two main points came from it:
-Patients highlighted how quickly their health could deteriorate without early intervention.
-Patients described the large amount of time spent in hospital, and how this negatively impacted their quality of life.
Both of these points highlighted the need for a new faster detection method that wouldn’t significantly increase burden of care already faced by patients.
Whilst we had built the synthetic biological detection systems, we needed to identify where we saw the device being implemented, and design it accordingly. If it was to be used in hospital clinics, patients would still have to travel long distances to use it.
Initially, we started to design the L.A.S.S.O. as a home device, to maximize convenience for the patients. During this process we discussed with patients whether they would want to see their results straight away, and the difficulty of representing this data in a meaningful way.
After speaking to patients and a psychologist at Ninewells, we were concerned about the psychological ramifications and impact on a patient’s mental wellbeing if The Lung Ranger showed that they had developed a chronic infection. However, it was clear that patients wanted more control and autonomy over their condition.
Home visits with nurses provided an alternative opportunity for us to implement the detection device within a support network patients are familiar and comfortable with. We decided to make a detection device, the L.A.S.S.O., which would be portable. This means that it could be taken by the nurse to a home visit and used at home, with the psychological support of the clinical care team on hand. Speaking to patients, nurses and clinicians at a later date, we decided that the data generated would be sent straight to the clinician via the L.A.S.S.O. Interface, to avoid misinterpretation of results by the patient and reducing any undue stress.
Clinical Microbiology
Current methods for detecting and identifying lung infections in CF patients take too long. Acute lung infections can rapidly become chronic biofilm infections, making them much more difficult to eradicate with antibiotics.
We wanted to improve current detection methods for respiratory pathogens in people with CF, and so we visited Dr William Olver in the Clinical Microbiology Laboratory in Ninewells Hospital to further understand this time consuming process and how we could improve upon it.
(Shown Above) Lung Ranger Jenny at the Clinical Microbiology Laboratory at Ninewells Hospital.
Current techniques depend on labour intensive culture dependent methods for identification of respiratory pathogens in clinical samples. On average, culturing the samples and informing treatment takes 2 weeks or longer if cultures have to be tested for specific antibiotic resistance.
The aim of The Lung Ranger is to identify specific respiratory pathogens from sputum samples in less than 1 hour by detecting the signalling molecules they produce.
The CF Clinical Care Team
Dr James ChalmersA chest physician at Ninewells Hospital and researcher in the Molecular Microbiology Division, Dr Chalmers has been one of our chief advisors with regards to CF Clinical Care.
Dr Helen Rodgers
A chest physician at Western General Hospital in Edinburgh, and at Ninewells Hospital in Dundee, Dr Rodgers introduced us to patients and the clinical care team in Edinburgh, allowing us to get a broader view of the impact of our device for CF patients.
Cystic Fibrosis Team Ninewells
Lawrie MacDougall (CF Clinical Nurse Specialist), Gill Brady (CF Clinical Nurse Specialist), Ali Smith (Physiotherapist), Alison Marshall (Dietician) and Ash Sinclair (Clinical Psychologist) make up the CF Clinical Team in Ninewells Hospital. Throughout the project they have been incredibly accommodating and welcoming each week, and have given us a holistic view of all the different aspects of care required in managing Cystic Fibrosis through their expertise in different disciplines. The team had been incredibly kind sharing their time and knowledge with us. We took the opportunity to share some of what we did in the lab with the team, and to introduce them to Synthetic Biology in action!
We wanted to understand what we were expecting of patients when we asked them to produce sputum samples in order to use our device. We needed to know whether it was reasonable for us to base our device around a certain amount of sputum brought up by the patients. To see for ourselves, Dave, Roddy and Jenny went to the Clinical Research Centre at Ninewells. Using nebulized saline solution, they were able to cough up sputum from their lungs. It was pretty unpleasant, and gave an insight into the daily life of someone living with CF, and also highlighted what we were expecting from patients.
