Meath Foundation Research Laboratory (MRFL) at TUH

Meath Foundation Logo
Contact name:Sian Cregan - Interim Laboratory Manager
Email:cregans@tcd.ie
The Meath Foundation Clinical Research Laboratory is the flagship clinical research laboratory on the hospital campus. It currently supports registered researchers from 12 disciplines across the hospital campus, which includes Clinical Medicine, Clinical Microbiology, Rheumatology, Gastroenterology, Pharmacy, Respiratory, Neurology, Endocrinology, Nephrology, Psychiatry, Clinical Chemistry and Geriatrics.

The Meath Foundation Clinical Research Laboratory is the catalyst that drives world-leading clinical research here at Tallaght University Hospital.

It is the investment by the Meath Foundation in the Meath Foundation Clinical Research Laboratory that is the principal driver for both our current strength and breadth of clinical research being undertaken at TUH.

Research Undertaken in the MFRL at TUH

Clinical Microbiology Research Group
Dr. Renwick's group in the department of Clinical Microbiology, TCD, run research projects on understanding the microbes (bugs) in the airway of children with cystic fibrosis (CF). CF is a multiorgan inherited disease and Ireland has one of the highest rates of CF worldwide, with one in 1,400 live births affected.

CF causes a thick build-up of mucous on the lungs and people with CF suffer repeated lung infections leading to lung damage and eventually, lung failure. Up to 95% of mortality is due to airway infections caused by bugs entering and colonising the lungs. Many of these bugs become resistant to antibiotics and therefore are very difficult to kill once established.

Dr. Renwick has several projects running, focusing on the newly discovered microbial communities in the CF airway. The CF airway harbours many bugs at one time, and this is called polymicrobial (many bugs) or a 'microbiome'. The AIrway Microbiome in CF (AIM CF) project employs advanced, cutting-edge DNA-based sequencing techniques to explore the diversity of bugs present in the airways of people with CF and to investigate whether more appropriate treatments could target the detrimental bacteria in these communities.

The Study of Polymicrobial INteractions in CF (SPIN CF), co-managed by Dr. Emma Reece, seeks to study the complex communications between bugs in these polymicrobial communities (yes bugs talk to each other!).

Our overarching aim is to discovery better ways to kill dangerous bugs in the CF airway and determine ways we can use signatures in these polymicrobial communities as red flags for predicting disease severity. These projects are funded by the Wellcome Trust, the Irish Research Council, TCD PhD Provost Award and the European Society of Clinical Microbiology & Infectious Diseases (ESCMID).

Helicobacter Pylori Infection & Antibiotic Resistance Research
During the year, Dr. Sinead Smith (Ussher Assistant Professor in Applied & Translational Medicine, TCD) and Professor Deirdre McNamara (Consultant Gastroenterologist, TUH and Associate Professor, TCD) initiated a nationwide research project on Helicobacter pylori (H. pylori) antibiotic resistance.

H. pylori is a bacterium (germ) that infects the stomach of approximately half of the world’s population. Although infection does not usually have serious consequences, some patients will develop stomach inflammation, ulcers or stomach cancer. Treatment has become challenging in recent years due to antibiotic resistance. Dr. Smith and Professor McNamara received an Applied Partnership Award from the Health Research Board to investigate the prevalence of H. pylori antibiotic resistance in patients attending different hospitals around the country. Laboratory aspects of the project are carried out at the state-of-the-art Meath Foundation Research Laboratory on the TUH campus.

It is anticipated that information from this research will be used to guide doctors in the most appropriate antibiotic combinations for the successful treatment of H. pylori.

The Efficacy and Safety of Psilocybin Therapy in Treatment Resistant Depression
Over the last two decades there has been a renewed interest in the therapeutic potential of psychedelics, such as psilocybin, the main component of magic mushrooms. Promising early studies showed that psilocybin, when administered with psychological support and under psychiatric supervision could lead to improvements in mood, anxiety and quality of life. These studies prompted large scale clinical trials of psilocybin therapy for treatment resistant depression (TRD).

Dr John Kelly and Professor Veronica O’Keane in TUH and TCD were among the site investigators in the international trial of psilocybin therapy for TRD, which began three years ago. Results from the trial, funded by COMPASS pathways were released this year. This trial of 233 participants, showed that psilocybin therapy at the higher dose of 25mg resulted in a significant improvement in depression, anxiety and quality of life. It also showed that the higher dose of 25mg was superior to 10mg and 1mg.

Dr. John Kelly and Professor Veronica O’Keane, together with a site in San Diego, also conducted the first ever study examining the efficacy and safety of psilocybin therapy in TRD in people who choose to remain on their SSRI antidepressant. This study of 19 people showed that psilocybin (25mg) therapy could also lead to significant improvements in depression in those taking SSRI antidepressants. Taken together, these studies will pave the way for a world-wide phase 3 clinical trial of psilocybin therapy for TRD in 2022 to determine whether psilocybin therapy will be approved as a much-needed additional treatment strategy for those who suffer from depression.

An expansion of psilocybin therapy research into other mental health disorders and an exploration of the potential therapeutic role of short acting psychedelics, such as Dimethyltryptamine therapy are also planned in the near future.

Research to Define Key pathways that predispose to chronic inflammatory diseases
The Donnelly Research group led by Professor Seamas Donnelly seeks to define key regulatory pathways that predispose to chronic inflammatory diseases such as Asthma, Pulmonary Fibrosis, COPD and Rheumatoid Arthritis.

Their work undertaken at the Meath Foundation Research Laboratory epitomises Translational Medicine where original bench based observations are translated to clinical disease.

They are particularly interested in:
▪ Development of novel compounds as anti-inflammatory/anti-cancer therapies
▪ Host environmental influences on the regulation of the inflammatory response
▪ Genetic profiling guiding disease diagnosis, prognosis and response to therapy
▪ Host/Pathogen interactions which predispose towards more aggressive infection
▪ How the faecal microbiome influences host immune responses
▪ Mitcochondrial stress and chronic inflammatory diseases
▪ Stem cell dysregulation in Long-COVID Syndrome

They use advanced cell and molecular biology techniques, in vitro and in vivo models to address these questions. It is their vision that this work will pave the way for specific tailored therapies which would attenuate key regulatory pathways in inflammatory diseases.

Ultrasound-Guided Biopsy Programme
Professor Ronan Mullan is a Clinical Associate Professor with Trinity College Dublin and Consultant Rheumatologist at TUH. In 2016, Professor Mullan established a translational ultrasound-guided biopsy programme at TUH through which he collaborates at both national and international level.

Professor Mullan’s research, which is carried out in the Meath Foundation Research Laboratory, focuses on understanding the mechanisms of action of inflammatory arthritic diseases such as Rheumatoid Arthritis and Gout. Currently Professor Mullan’s research group is assessing the role of NLRP3 inflammatory pathways as well as the potent suppression of inflammation by a novel small molecule inhibitor on ex-vivo tissue samples and primary blood cells taken from Gout patients. Gout is an episodic destructive inflammatory arthritis, triggered by innate inflammatory responses to monosodium urate crystals. Gout affects 2% of adults and is now the leading cause of inflammatory arthritis within developed countries. This study could potentially lead to a clinical trial of MCC950 for the treatment of Gout.

Clinical Trials & Biorepository Development

Clinical trials are essential in modern evidence-based medicine and form the cornerstone of making today’s research tomorrow’s treatment. The facilities at the MFRL are enabling TUH clinical researchers to collect the samples necessary to contribute to international clinical trials. The laboratories have been approved for clinical trial in Geriatrics and Gastroenterology in addition to the two ongoing clinical trials. The laboratories have been successfully audited by the Health Products Regulatory Authority (HPRA) for an ongoing trial.

A vast biorepository has been developed in the laboratory and it facilitates one of the most significant functions of the Meath Foundation Research Laboratory; biobanking of unique patient samples. Many of these samples are subsequently shipped to collaborators throughout the world enabling TUH clinical researchers to contribute to international research.

Primary Cell Tissue Culture

The upgraded dedicated primary tissue culture facility within the Meath Foundation Research Laboratory has enabled the rheumatology group to isolate synoviocytes from biopsy samples taken from inflammatory arthritis patients. In the past three years samples have been collected from over 100 patients. These cell cultures are being used for proof of concept research studies and are making a substantial contribution to other studies within TCD through collaborations.

This facility has also enabled the clinical medicine group to culture cells from bronchoalveolar lavage samples from patients with sarcoidosis. In December 2021, the department of Clinical Medicine began a new project to investigate how changes in stem cells contribute to Long COVID-19 clinical phenotypes in collaboration with National University of Ireland, Galway NUIG.

Molecular & Cell Biology 

The MFRL is equipped with a full molecular analysis suite. The quantitative PCR platform is currently being used by Clinical Microbiology to perform high-specificity detection of pathogens, in particular Aspergillus fumigatus, Stenotrophomonas maltophilia and Pseudomonas aeruginosa, and develop multiplexed systems for detection of complex infections. The Gastroenterology group have been using the platform to analyse gene expression profiles in the stomach during Helicobacter pylori infection in order to identify predictive biomarkers and therapeutic targets for H. pylori-associated disease.

The facility for performing proteomic analysis and immunoassays is in constant use in the lab. The Gastroenterology, Neurology and Clinical Microbiology departments are using these platforms for various projects including the detection and quantification of inflammatory cytokines from clinical samples.

Teaching & Training

Teaching and training is undertaken in the MFRL, with Undergraduate students from the Department of Microbiology in the Moyne Institute TCD, Medicine, MSc students of Healthcare Infection TCD and Pharmaceutical Sciences TCD carrying out supervised research projects as part of their degree and master studies. The facility is an excellent learning environment which provides students with “real life” opportunities to implement theoretical knowledge. 

Outputs from MRFL- based research

In the five years since the provision of strategic funds for the upgrading of the Meath Foundation Research Laboratory by the Meath Foundation, the number of publications in international peer reviewed publications has increased by 50%. This reflects the significant increase in clinical research activity on the hospital campus principally driven by the provision of first-class on-site laboratory facilities.