People We Worked With

As well as the students, public and patients we worked with throughout the project, we are incredibly grateful for the support and advice we gained from a wide range of professionals.

Dr Tony Cutler - Wellcome Trust Centre for Human Genetics

As an immunologist specialising in Type 1 diabetes and autoimmune diseases, Dr Cutler provided us with an invaluable insight into the pathogenesis of autoimmune diseases and how anti-inflammatory molecules may have the potential to have therapeutic effects. We met with him during the early stages of the project to understand whether the production of IL-10 may have beneficial anti-inflammatory effects in individuals suffering from autoimmune diseases. He highlighted the importance of safety, and encouraged us to speak to patients and clinicians to understand how a GM probiotic may be accepted in clinical settings.

Professor Simon Travis FRCP - Professor of Clinical Gastroenterology

Professor Travis provided us with valuable advice based on his insight as a practising clinician. He believed that a GM probiotic would be a safe treatment, although he advised us to consider the possible complications of the treatment escaping into the environment when excreted by patients in areas with poor sewage systems. In light of this, we designed a kill switch to ensure that our bacteria will not function when outside of the human gut. Professor Travis also advised us to focus our efforts on the treatment of autoimmune diseases of the gut, as opposed to autoimmune diseases in general, based on the heterogeneous nature of different autoimmune diseases. He also recommended that we consider the strain of bacteria we would use in the final therapeutic product, since it is vital that the bacteria adheres to the wall of the gut. He provided us with information on clinical trials using IL-10 to treat Crohn’s disease, and recommended the use of IL-10 therapy as opposed to other anti-inflammatory molecules (such as anti-TNFa).

Dr Hannah Chen - Translational Gastroenterology Unit, University of Oxford

Dr Chen gave us further guidance about the treatment of Crohn’s disease and other inflammatory diseases of the gut, highlighting the fact that the symptoms and cause of Crohn’s disease are heterogenous. Her insight made us consider the range of inflammatory markers that vary in individuals with Crohn’s disease, prompting us to undertake further research into biomarkers for Crohn’s disease. Dr Chen recommended reading about certain research studies, and this enabled us to find evidence to demonstrate that luminal NO is a suitable biomarker for Crohn’s disease, as well as providing quantitative data for use in modelling. Dr Chen also discussed the importance of the microbiome and the general lack of understanding among the public, which encouraged us to create an information leaflet about probiotics and the microbiome.

Professor Chris O’Callaghan - Nuffield Department of Medicine

Professor O’Callaghan’s knowledge of biomarkers of inflammation and immune functioning provided us with important advice in the use of biomarkers in the design of our probiotic. He highlighted key studies involving biomarkers, such as evidence to show that exhaled NO is correlated to disease severity in asthmatics, to demonstrate the potential of developing an NO-based treatment method. He introduced us to the idea of altering the structure of IL-10, such as by conjugation to another molecule, to increase the transport of IL-10 to sites of inflammation. He encouraged us to research the evidence from clinical trials using Dekavil - IL-10 conjugated to an antibody - to treat arthritis, and to consider whether similar conjugation methods could be use in our product to prevent protease breakdown within the gut lumen.

Dr Chris Butler - Nuffield Department of Primary Care Health Sciences

Dr Butler’s experience in Primary Care provided us with an important understanding of patient’s perceptions and their likely responses to the use of a GM probiotic. Dr Butler believed that patients understand the concept of ‘good’ and ‘bad’ bacteria existing, but believed that the majority of patients would still be surprised, and probably sceptical, about the use of taking bacteria as a treatment. This reinforced the importance of educating the public about probiotics and the benefits of a diverse microbiome, therefore encouraging us to develop an educational leaflet about probiotics and include this subject as one of the key focuses in our Long-term Public Education Plan. Dr Butler is the Principal Investigator of the PRINCESS (Probiotics to reduce infections in care homes) Trial, so provided information about the effectiveness of probiotics. He provided information about the microbiome becoming less diverse with age, but informed us that there is currently no evidence to suggest that probiotics become less effective with age - this suggested that our therapeutic should still be functional in more elderly patients.

Professor David Greaves - Sir William Dunn School of Pathology, University of Oxford

Professor Greaves highlighted the importance of ensuring that the delivery of IL-10 is controlled, drawing upon evidence from his own experiments that demonstrated the health risks associated with excessively high expression of IL-10. He provided us with papers and further reading which allowed us to understand the range of healthy concentrations of IL-10 that we could use for modelling the adenine-induced negative feedback loop.

Professor Luzheng Xue - Nuffield Department of Medicine, University of Oxford

Professor Xue gave us useful advice on the molecular and cellular mechanisms involved in the pathogenesis of inflammatory diseases. He recommended that we should research the other sources of NO, such as endothelial cells, and to ensure that this is considered when modelling the system.

Dr Nick Thomson - Quadrum Institute, Norwich

Dr Thomson gave us an invaluable insight into the delivery mechanisms of probiotics and how to ensure the probiotic bacteria establish a niche within the microbiome. He gave us guidance on the types of strain to use in the probiotic product, introducing us to studies demonstrating that VSL#3 (a polybiotic solution containing many different probiotic bacterial strains) can be taken orally to improve Crohn’s disease. This gave us useful direction for our research into probiotic strains and probiotic delivery. He also gave us useful ideas for areas of further research to test our product, such as using a model colon - with varying concentrations of oxygen and carbon, to test the bacteria in environments similar to the natural colon. He also praised our kill switch designs, again highlighting the importance of addressing the safety concerns associated with GM probioitcs.

Dr Chris Barnes - Department of Cell and Environmental Biology, UCL

Dr Barnes provided useful information about the colonisation of probiotic bacteria in the gut, demonstrating the importance of choosing the right chassis. He also suggested that we should focus on controlling the bacterial population size and should consider quorum sensing as a method of ensuring that the population remains at a constant level.

Dr Sam Parsons - Oxford Centre for Emotions and Affective Neuroscience

Dr Parsons is a psychologist and he shared information about the psychological impact of autoimmune conditions, including the psychological impact of chronic pain, isolation, stigma, and phobias of hospitals/needles. This enabled us to understand further complications of autoimmune diseases, and encouraged us to choose an oral form of probiotic delivery in order to create a minimally invasive, easily administered treatment.

Dr Michael Morrison - Centre for Health, Law and Emerging Technologies (HELEX)

Dr Morrison met with us on multiple occasions to discuss the law and regulations that would be relevant to the development of our product. He gave us guidance on the various regulations that would govern how our product could be used clinically, and gave us an understanding of the processes required during clinical trials. In light of our work with Dr Morrison, we created a proposal on the safety of GM probiotics, a long-term public education plan, and theoretical plans for completing clinical trials and the manufacture of our probiotic.