The launch of the Translational Safety Biomarker Pipeline (TransBioLine) Project
The launch of the Translational Safety Biomarker Pipeline (TransBioLine) Project
17th April 2019
INNOVATIVE MEDICINES INITIATIVE LAUNCHES TRANSLATIONAL SAFETY BIOMARKER PIPELINE PROJECT TO ENABLE DEVELOPMENT AND IMPLEMENTATION OF NOVEL SAFETY BIOMARKERS
The Innovative Medicines Initiative (IMI) today announced the launch of the Translational Safety Biomarker Pipeline (TransBioLine) Project, a five-year program to generate exploratory and confirmatory data supporting regulatory qualification and acceptance of novel safety biomarkers for five target organ systems (kidney, liver, pancreas, vascular, and central nervous system) for application in drug development.
The TransBioLine Project is a consortium of 27 partners across pharmaceutical companies, small and medium-sized enterprises, and academic institutions from 10 European countries, and is coordinated by the University of Zurich with Pfizer Inc. as the industry lead. It is funded by the IMI Joint Undertaking as a public-private partnership, with a budget of 28M€ and will be active through 2024.
“One of the major gaps in drug development is the lack of qualified safety biomarkers with acceptable precision and accuracy for safety monitoring during clinical development,” said Shashi Ramaiah, Executive Director, Pfizer Drug Safety Research & Development and TransBioLine Lead Scientist. “The TransBioLine Project provides a unique opportunity to access a large expert and knowledge network, including data and samples from clinical trials, to enable the global safety qualification of identified novel biomarkers. Implementing qualified safety biomarkers in early clinical trials will mitigate safety attrition of promising drug candidates and advance projects to clinics through higher-quality and better-informed decision making.”
Michael Merz, Consortium Coordinator, University of Zurich, said, “This is one of the largest public-private partnerships of European and American scientists that focuses on the development and regulatory qualification of new safety biomarkers. These include indicators of tissue damage like liquid biopsy, biomarkers that could facilitate patient stratification, and standardized tests for detection of these biomarkers. These new markers are ultimately expected to not only improve safety of new and approved drugs, but also to contribute to better diagnosis and management of acute and chronic diseases. It is really exciting to see years of enthusiastic preparation translating into this project going forward now.”
When the project ends in 2024, the consortium will have established an infrastructure and processes to continue biomarker research across a comprehensive network of industry, academic institutions, and small and medium-sized enterprises, and it will be able to provide the scientific community, industry and patients with detailed data and information across a large spectrum of advanced safety biomarkers.
Professor Guruprasad Aithal, the Deputy Academic Co-ordinator for TransBioLine and the ‘Drug-induced liver injury (DILI)’ work package lead, said- ‘TransBioLine is an enormous opportunity to turn science into clinical practice to improve safe use of medication. It will boost NIHR Nottingham BRC researchers who have led discoveries in DILI field over the past 2 decades’.
Doctors Jane Grove and Stuart Astbury are contributing to the discovery and evaluation of new tests to identify liver injury early and reduce patient harm; Ms Beth Robinson will be project coordinator for the DILI work package.
TransBioLine DILI work package team in Nottingham
About the Innovative Medicines Initiative
The Innovative Medicines Initiative is a partnership between the European Union and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA). It is working to improve health by speeding up the development of the next generation of medicines, particularly in areas where there is an unmet medical or social need.
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA companies.
Could anti-sickness drug end the misery for IBS patients?
Could anti-sickness drug end the misery for IBS patients?
24th March 2019
Could a commonly-prescribed anti-sickness drug be the answer for the 1.3 million people in the UK who suffer the pain and misery of irritable bowel syndrome with diarrhoea (IBS-D)?
A nationwide clinical trial, TRITON, led by Professor Robin Spiller in Nottingham will assess the medication ondansetron, which is currently used by doctors to help cancer patients cope with the nausea and vomiting associated with chemotherapy, radiotherapy and surgery.
The research will aim to establish whether a much lower dose of the drug could also be a successful treatment for the abdominal pain and urgent bowel movements typically experienced by IBS patients. Read the full press release on the University of Nottingham’s website
The TRITON study has also been featured in the Mail on Sunday Karen Andrews, Patient Advisory Group (PAG) member, shared her story as one of the first patients to benefit from the study.
If you would like to know more about the TRITON study and see if you are eligible to take part, please contact Dr David Gunn: David.Gunn@nottingham.ac.uk 0115 970 9966
We had a great day at our GI & Liver Disorders BRC and NDDC Showcase on Friday 7th December at the Doubletree Hilton Hotel.
Research area leads and juniors presented their research highlights from the past year and upcoming research projects. Thank you to all the speakers for showcasing the breadth and depth of research activity that they are all involved in. We also had a poster session running throughout the day showcasing the work from our PhD students.
With a wide range of topics presented over 5 sessions throughout the day, it was a really interesting programme
Positive feedback was received from the delegates and speakers:
Prof Guru Aithal, GI & Liver theme lead: ‘It is heartening to see, new researchers, collaborations and new areas emerge.
Delegate: ‘Impressive presentations in terms of scientific vigour, communication and data analysis. An excellent overview of the exciting research conducted in the BRC’
Delegate: ‘Complexity of the subject matter was conveyed in an easy to digest way thanks to the presenter’s skills and well prepared slides’
Congratulations to all the junior presentation and poster prize winners:
Oral presentations:
1st prize: Victoria Wilkinson-Smith ‘Effect of Kiwifruit on Gastrointestinal Symptoms: A Mechanistic MRI Study in Healthy Volunteers’
2nd prize: Hannah Williams ‘Increased small bowel permeability is associated with significantly increased T2 measures of the small bowel wall’
Poster presentations:
1st prize: Colin Crooks ‘Modifying Topic Modelling To Identify Prognostic Risk Factor Patterns’
2nd prize: Asseel Khalaf ‘Alteration in small bowel motility, gut peptides and patient’s symptoms in active Crohn’s disease’
Professor Guru Aithal and his team comprising of Dr Liz Simpson, Dr Moira Taylor, Laura Miller, Dr Sally Hibbert, Dr Stephen Bawden, Amrita Vijay and Bethany Robinson travelled to Trivandrum, India in November.
They are working on a collaborative research project with Dr Thrivikrama Shenoy and Leena Mohan, who are based at the Population Health Research Institute (PHRI), developing new approaches to tackle rising levels of fatty liver disease in India.
A ‘fatty liver’ is when more than 5-10% of a person’s liver is fat. This condition puts people at much higher risk of developing diabetes and heart disease. In the UK, fatty liver is twice as common among people of South Asian descent compared with whites: 2 in 10 versus 1 in 10. In some parts of India (e.g Kerala) the prevalence is 5 in 10. We believe that this higher risk is in part caused by dietary and lifestyle factors.
The overall goal is to improve the metabolic health and well being of individuals and reduce the burden of non-alcoholic fatty liver disease (NALFD) and concurrent metabolic syndrome in Kerala.
For the week the team hosted ‘Fighting Fatty Liver in Trivandrum’ workshops with Dr Shenoy and Leena for the PHRI social workers who will be delivering the study in Trivandrum. The team discussed the protocol, recruitment, dietary intervention, yoga schedule and how they will facilitate behaviour change.
Congratulations to Andy Wragg (Patient & Public Involvement Facilitator) who has been nominated in the Research and Innovation category for the NUHonours Awards 2018. Well done Andy!
Congratulation to Shellie Radford for winning her award at the R&I Thank You Event last week. Very well deserved!
Congratulations to The Scarred Liver Project team
Congratulations to Dr Neil Guha and The Scarred Liver Project team on their win at the University of Nottingham Knowledge Exchange and Impact Awards! Very well deserved! Great work team!
The Knowledge Exchange and Impact Awards celebrate the contribution of our University’s research to society and the economy. Inspirational award winners
Dr Rebecca Harris, Dr Neil Guha & Dr Jane Chalmers collecting their award
Nottingham a major partner in a new European Academic Liver Disease Network
Nottingham a major partner in a new European Academic Liver Disease Network
6th November 2018
Adverse liver reaction from medications are rare, but have serious consequences including life threatening acute liver failure. The European Cooperation in Science and Technology (COST) has launched a new network involving 51 partners across 16 Countries in Europe and worldwide to bring together scientists, clinicians, industry and regulators to focus on key challenges in this area.
Experts from a diverse disciplines including drug development, clinical practice and medicines regulation have formed the ‘Prospective European Drug-induced Liver Injury Network’ Chaired by Prof Raul Andrade, University of Malaga and Prof Guruprasad Aithal, Gastrointestinal and Liver Disorder Theme lead of NIHR Nottingham BRC at the University of Nottingham and Nottingham University Hospitals NHS Trust, as the Vice-Chair on the COST Action Management Committee. Dr Jane Grove, Assistant Professor, Nottingham Digestive Diseases Centre, University of Nottingham is also the co-leader of one of the working groups.
‘Pro-Euro DILI network provides an excellent opportunity for scientists, clinicians, small and medium enterprises, pharma and regulators across Europe and beyond to get together and make co-ordinated efforts to address some of the most obdurate problems related to drug-induced liver injury’
Prof Guruprasad Aithal
The COST Action has created a multi-disciplinary network hosting conferences, training schools and researcher exchange placements over the next four years to promote a highly innovative and translational research programme striving to pre-empt and prevent Drug-Induced Liver Injury (DILI).
The University of Nottingham 2018 team has been awarded a prestigious Gold Medal and was nominated for ‘Best New Composite Part’ at the recent International Genetically Engineered Machine (iGEM) competition in Boston, USA.
It is the first team from Nottingham to win a Gold Medal, which was awarded to the team at the iGEM Jamboree event in Boston on Sunday 28th of October 2018.
iGEM
The iGEM competition began in Jan 2003 and currently attracts over 400 teams, from more than 45 countries and annually exceeds 5000 global undergraduate and post-graduate student participants. Teams use the principles of synthetic biology, the “Engineering of Biology”, to design biological parts, devices or systems to address a real-world problem or to perform a novel, previously unseen function. The best ‘parts’ of every project are then submitted in the form of a ‘BioBrick’ to the iGEM BioBrick registry for use by others.
The Team
Nottingham’s team was composed of ten undergraduate students drawn from the Schools of Life Sciences, Biosciences, Computer Science, Mathematics and Social Sciences. For the duration of their project they were embedded within BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) at Nottingham, under the overall guidance of Nigel P Minton and Philippe Soucaille and under the close supervision of a dedicated multidisciplinary team comprising Louise Dynes, Daphne Groothuis, Dr Christopher Humphreys, Dr Carmen McLeod, Dr Michaella Whittle and Dr Craig Woods.
Clostridium dTox
The team’s innovative synthetic biology project, Clostridium dTox; it’s not so difficile, aimed to develop a novel therapy for the treatment of disease caused by the superbug Clostridium difficile.
C. difficile infection is the most common cause of antibiotic-associated diarrhoea in the Western World and is a big problem in hospitals and care-facilities. The disease symptoms are caused by the release of two major toxins, TcdA and TcdB by the bacteria. The use of broad-spectrum antibiotics to treat disease causes a reduction in the natural diversity of the gut microbiota. It is this reduction in gut flora biodiversity which allows C. difficile to take advantage. It is thought that non-toxigenic C. difficile present in the gut microbiota could act as a possible probiotic, out-competing toxigenic C. difficile.
The aim of the project was to engineer a C. difficile bacteriophage to produce factors that would bring about suppression of toxin production. The expression of both toxin genes (tcdA and tcdB) were repressed by targeting their mRNA using either antisense RNA (asRNA) or CRISPR interference (CRISPRi) technology (dCas9). The ultimate aim is to produce a C. difficile-specific bacteriophage therapeutic which ablates toxin production without significantly affecting the native gut microbiota.
The team was also nominated for ‘Best New Composite Part’. A composite part is a functional unit of DNA consisting of two or more basic parts assembled together. These must include all characterization information and be added to the Registry.
Human Practices and Public Engagement
The team devised a number of activities that explored how Clostridium dTox could impact society. This included mining and carrying out a sentiment analysis of data from hundreds of social media comments on an online phage therapy video and exploring the current legislation surrounding phage therapy. They also researched what makes C. difficile such an important issue to society and how their project can help make a positive impact on communities by working towards the development of a novel therapy for its treatment. Finally they held a discussion group with non-scientists, and interviewed five leading scientific experts in the field, including the UK Public Health England lead on C. difficile infection, to understand how the team could make their project as effective as possible.
Public engagement was an important focus for the team, which developed hands-on workshops to communicate the project in local schools, libraries and to staff and students at the University. The team members have also been busy promoting their project via a range of social media platforms as well as by publishing articles in a local newspaper and in the University of Nottingham’s Impact Magazine.
Gold
All of these aspects enabled the team to produce a project of high enough quality to win a Gold Medal at the Giant Jamboree, recognising the fulfilment of all the competition criteria. The Gold winning team members were; Lucy Allen, Hassan Al-ubeidi, Ruth Bentley, Sofya Berestova, Eun Cho, Lukas Hoen, Daniel Partridge, Varun Lobo, Fatima Taha and Nemira Zilinskaite.
What the Judges said
“Great project, great wiki!! You just light up so many questions in my mind and actually this is the key of synthetic biology! Thank you so much for your effort and all hard work!”
“Super interesting idea to use temperate phages for this! …. You are clear on your achievements and reasoning throughout, which is super refreshing. Great effort!”
Sponsors
Nottingham’s iGEM team was generously supported by the University of Nottingham’s Research Priority Area in Industrial Biotechnology, through grant funding from the Wellcome Trust, the Biotechnology and Biological Sciences Research Council (BBSRC) and the National Institute for Health Research (NIHR) via the Nottingham Digestive Diseases Centre, by generous cash donations from Don Whitley Scientific Ltd, LanzaTech and Seres Therapeutics and through in-kind support from Qiagen, Millipore Sigma, Promega, Eppendorf, New England Biolabs, LabFolder and Snapgene.
Collaborators
We are also grateful for the support given by the following collaborators: Team Biomarvel Korea and the teams from Imperial College London and the University of Warwick.
New clinical trial where stem cell transplants will be used in treating Crohn’s disease
New clinical trial where stem cell transplants will be used in treating Crohn’s disease
10th August 2018
Nottingham scientists and clinicians are involved in a new clinical trial which aims to use stem cell transplants to grow a new immune system for people with untreatable Crohn’s disease – a painful and chronic intestinal disease which affects at least 115,000 people in the UK.
Crohn’s disease is a long-term condition that causes inflammation of the lining of the digestive system, and results in diarrhoea, abdominal pain, extreme tiredness and other symptoms that significantly affect quality of life.
Professor Yash Mahida, Professor of Medicine at the University of Nottingham and one of the researchers leading Gastro-intestinal research as part of the NIHR Nottingham Biomedical Research Centre said: “This trial has the potential to transform patient’s lives which are greatly impacted by the debilitating effects of Crohn’s disease. It is an important part of the work we are doing at the Nottingham Biomedical Research Centre to advance our knowledge of inflammatory bowel disease.”
Professor Krish Ragunath hosted 2 Research fellows here at the Queen’s Medical Centre (QMC), Nottingham over the past few months. They each spent time within the Endoscopy unit at the QMC working with Prof Krish Raguanth, Dr Jacobo Ortiz and the endoscopy team.
The feedback we have recieved from them both, thanking Prof Ragunath and his team at the QMC can be read below.
Dr David Janelidze, ESGE Fellow from Ukraine:
“....and at the end of training in a top rated clinic of Europe – Queen’s Medical Center and City Hospital, Nottingham, United Kingdom– in which I was honored to have a ESGE fellowship (Module I), I would like to express my gratitude to ESGE, especially Professor Krish Ragunath and Doctor Jacobo Ortiz and all the doctors from gastroenterology department and endoscopy unit. I was met warmly. All of them shared their professional knowledge and skills with me, always found time answer to my questions. I had ability to look and participate in endoscopic procedures with them, had a discussion about the management of patient with various nosology. My staying here was very interesting”
Ekaterina V. Ivanova, Research Fellow from Moscow:
“This week has been so busy that, sorry, but only now I sat down at the computer to express my gratitude for those days that I spent in your Department,
for the pleasant moments when we could talk, for Your hospitality and knowledge that I received.
Thank You for the opportunity You have given to visit different cities in GB as well as conferences and hospitals it is a really great experience.
In addition I would like to thank You for the last week of “dipping” in the topic of Barrett’s esophagus, when everything became more or less structured on this topic in my mind=)
Thank you for Your time and agreeing to give a lecture on the teleconference with Khabarovsk. For them it was a great event. We did it for the first time!”
Developing novel anti-fibrotic therapeutics for liver disease using bespoke 3D cell culture systems and tissue bioanalysis
Project Description:
Integrins are receptor proteins responsible for mechanosensing of tissue stiffness during scarring (fibrosis) in response to injury. Fibrosis in the liver leads to the development of cirrhosis which can progress to cancer, a major cause of mortality. Integrin avα1 is significantly elevated in chronic liver disease and administration of an inhibitor compound shows promise in reducing in fibrosis in a fibrotic mouse model.
This project will provide much-needed information about role of integrins in the process of fibrosis underlying the development of chronic liver disease which is a major global public health challenge. It will also establish integrins as a valid therapeutic target and analyse novel integrin inhibitors with potential to reverse fibrosis.
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