A new research hub in Nottingham will use the UK’s largest collection of stored tissue samples to speed up the development of diagnostic tests for lung and digestive diseases. The problem is that promising new biomarkers—biological molecules that signal disease—often stall in the lab because there is no clear pathway to turn them into tests doctors can use. This hub will connect the region’s vast tissue archives, patient databases, and computational expertise to push discoveries through that pipeline. For example, chronic obstructive pulmonary disease kills 25,000 people in the UK each year, and idiopathic pulmonary fibrosis kills half of patients within three years of diagnosis. Better diagnostics could catch these diseases earlier and guide treatment. If successful, the hub will produce new molecular tests and computer models that can be applied to respiratory, liver, and gastrointestinal diseases—and likely to other organ systems as well. It will also train the next generation of molecular pathologists through master’s programmes and summer schools, meeting a growing NHS and industry need. The work builds on existing patient cohorts, including 550 people with IPF, 400 with cystic fibrosis, and 10,000 with hepatitis C, ensuring that discoveries can be tested quickly in real patients.
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The context of the research There have been substantial recent investments in Stratified Medicine and Analytical Science by the MRC and EPSRC. A recent MRC Pathology Review has highlighted the need for a robust pathway and capability for the development and adoption of new diagnostic tests. Nottingham Molecular Pathology Node will provide the necessary path and capability to fill the needs identified by the MRC review. Aims and objectives To create an infrastructure to drive molecular diagnostic biomarker research down the development pathway utilizing molecular pathology/biobanking strengths and integrating computational/bioinformatics expertise This initiative will bring together Nottingham's expertise in molecular pathology, East midlands Pathology (Empath) which is the largest clinical pathology service in Europe and has the largest repository of archival tissue in Europe, Nottingham Health Sciences Biobank which is the CRC UK National Biobank co-ordinating centre and Nottingham's Advanced data Analysis Centre (ADAC) which has strong computational expertise including bioinformatics, artificial neural networks, statistics and data interpretation skills for integrating knowledge from several platforms. To use this infrastructure where Nottingham has existing translational research strengths Our strategy will be to use the infrastructure to produce world-class innovative research and progress new biomarkers from discovery, down the development pathway into the clinic. Nottingham's major clinical research strengths are: (i) Respiratory and (ii) GI/liver diseases where we have critical mass, expertise, patient cohorts and infrastructure supported by MRC, NIHR, research charities, EU and industry funding. To address areas of unmet clinical need Chronic Obstructive Pulmonary Disease (COPD) affects over 1 million people in UK and kills 25,000/year. Idiopathic Pulmonary Fibrosis (IPF) is commoner than all leukaemias combined kills 50% within 3 years of diagnosis. Lymphangioleiomyomatosis (LAM) has no effective treatment and we host the UK centre. Cystic Fibrosis (CF), the commonest genetic disease and median age of death is 35-40 usually due to Pseudomonas infection. Hepatitis B/C affect more than 500,000 people in the UK. H. pylori affects 1 in 6 people in the UK and causes peptic ulceration and gastric cancer. To use existing large patient cohorts to facilitate translation Nottingham Respiratory Research Unit (NRRU) has well-phenotyped cohorts (n) including IPF (550), LAM (100), CF (400), and COPD (400). We contribute to national/international collaborations including IMI UBIOPRED, MRCMAP COPD, NIHR Respiratory TRP, MRC Rare Diseases Consortium, CRAFT Consortium. The NIHR Nottingham Digestive Disease Biomedical Research Unit (NDDBRU) hosts HCV Research UK, a national cohort (10,000) and clinical database/biorepository, and is a MRC Stratified Medicine Consortium STOP-HCV member. NDDBRU has non-alcoholic fatty liver disease (NAFLD; 300), compensated cirrhosis (200), Hepatitis B (200) and H.pylori cohorts. To use the infrastructure to train the next generation of molecular pathologists We will run high quality Master' levels programmes, short taught courses and summer training schools meeting NHS/industry needs for molecular pathologists in the genomic medicine era. NMPN will provide a platform for aligning ACL posts, PhDs and MSc projects. Potential applications and benefits Our approach will develop world leading translational molecular diagnostic capabilities in GI/liver and respiratory diseases. The work will lead to the development and clinical application of biomarkers/molecular diagnostics and computer modeling algorithms in several important infective, inflammatory and fibrotic diseases of the respiratory, GI systems and liver and will likely be applicable to diseases in other organ systems. It will benefit patients, scientists, industrial partners and the health and wealth of the nation.
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