Sepsis is a major challenge in the intensive care unit, where it is one of the leading causes of death. It arises unpredictability and can progress rapidly. Globally there are an estimated 30 million cases of sepsis each year which results in more than 8 million deaths in adults and 5 million deaths in children. Of those who do survive a further one third will die in the following 12 months, those who survive often face life-long consequences, such as new physical, mental and cognitive problems. Although this number is gathered from several sources, all content to the fact that it is likely an underestimate and therefore may very well be the leading cause of mortality worldwide. Currently, there are no approved drugs on the market to control the underlying pathophysiology that triggers the dysregulated host response to sepsis and therefore the management plan focuses on reducing the infection through the use of aggressive intravenous antibiotic therapy and source control. Therefore the cardiovascular infection research group is investigating a therapeutic option that acts early to prevent bacteria binding to the host vascular endothelial cell in the first place would be commercially advantageous as it will prevent the infection from progressing to septic shock and a life-threatening situation as a result of multi-organ failure.
Funded by: Science Foundation Ireland, Enterprise Ireland, Irish Research Council, British Heart Foundation, Health Research Board, Wellcome Trust
I wanted to congratulate everyone for their significant contributions to recent RCSI Research Day. MCT’s presence was strong on the day with a number of keys oral and poster presentations from across the four MCT research pillars.
In particular, a huge congratulations to:
Dr Joan Ni Gabhann for the Most Highly Cited RCSI Senior Authored Paper with Industry Collaboration 2012-2016 for her paper ‘Btk regulates macrophage polarization in response to lipopolysaccharide’.
Rebecca Watkin (PI Prof Steven Kerrigan) and Edmund Gilbert (PI Prof Gianpiero Cavalleri) who jointly won the best postgraduate oral presentation, sponsored by Bio-Sciences Limited, for their presentations on ‘S.aureus induced miR330-3p expression triggers abnormal permeability in an ex-vivo 2D model of sepsis’ and ‘The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland’, respectively.
Prof James O’Donnell (ICVB) who won the Clinician CEO Innovation Award.
Dr Ingmar Schoen for his novel Invention Disclosure.
Camille Hurley (PI Dr Darran O’Connor), Edmund Gilbert (PI Prof Gianpiero Cavalleri) and Conor Duffy (PI Claire McCoy)for winning inaugural RCSI International Secondment Awards.
Finally, well done to Dr Claire McCoy for giving an inspiring and heartfelt presentation about her SFI President of Ireland Future Research Leader Award.
Last week was another superb week for circadian research in the Molecular and Cellular Therapeutics Department. The Curtis Laboratory published our first big paper on the immune body clock in Nature Communications. This study originated back in 2013. I was still a postdoc in Prof. Luke O’Neills laboratory at Trinity College and was intrigued by some of the studies that showed that multiple sclerosis (MS) was affected by the circadian disruption. A key study showed that teenagers who work shift work before the age of 18 are more susceptible to multiple sclerosis in later life. I wondered if we would see any differences in multiple sclerosis if we disturbed the immune body clock. I approached Prof. Kingston Mills also at Trinity College, who is one of the world leaders of multiple sclerosis and has a key mouse model that recapitulates certain features of MS, called experimental autoimmune encephalomyelitis (EAE). The first experiment we conducted was to see if a mouse which does not have the molecular clock in macrophages was more susceptible to disease, and low and behold it was! This project was driven by one of the most talented researchers that I have ever had the pleasure of working with, Dr. Caroline Sutton, who is a senior postdoctoral fellow in Prof. Mills lab. This project is a great example of collaboration between multiple labs, Mills, O’Neill and my own new group here at RCSI.
And if that wasn’t enough! We also hosted the circadian expert Prof. Qing-jun Meng for our second institutional seminar series on Thursday. Prof. Meng is a world expert on clocks in the musculoskeletal system at University of Manchester. I met Qing-jun in 2013, and have followed his research intensely. He has made seminal discoveries on the impact of the clock on cartilage and invertebral disk function and how this leads to diseases of ageing, such as osteoarthritis and lower back pain. He had the audience enthralled for an hour with his rhythmic images of cells glowing with 24-hour rhythms, and his use of Google searches. It was an absolute pleasure to have Qing-jun with us for the day, and I hope that we can have him back again in the near future.
Some news features on the article can be found here:
On November 14th, we welcomed almost 50 secondary school students at our Department for Lab Safari. The event was designed to encourage young people to consider a career in Science, Technology, Engineering, Maths and Medicine through hands-on experience and demonstrations prepared by our researchers. We developed 6 different workstations focused on Cancer biology and biomarkers, Drug Discovery, Multiple Sclerosis, Human Genetics and Immunology/Body clock
The event was opened by Prof. Tracy Robson, Head of MCT, sharing her career path in research and lessons that she learnt. Dr Avril Hutch, Head of RSCI Equality and Diversity Unit, also spoke about stereotypes in STEMM careers and having an awareness of unconscious bias.
Our workstation was led by Caragh Stapleton, Katherine Benson and Edmund Gilbert, centered around human genetics. Our activity set out to teach participants about inherited traits and demonstrate how variation in our DNA influences our physical attributes. We investigated a number of traits including PTC taster (using PTC taste strips), colour blindness, widows peak, tongue rolling, attached earlobes, bent little finger, eye colour and red hair. Each participant noted whether or not they had the given trait and we then discussed the hypotheses of the genetic variants influencing the different traits.
Our workstation was led by Olga Piskareva and John Nolan. We explained the concept of biomarkers and the importance of discovering novel biomarkers for neuroblastoma, a childhood malignancy. Various chromosomal aberrations can be biomarkers of neuroblastoma aggressiveness. One of the strongest predictors of rapid neuroblastoma progression is MYCN status. We selected several neuroblastoma cell lines with known MYCN status providing a good illustration of biomarker’s quantity. Using immunodetection, we visualised the differences in the MYCN presence.
Our workstation was led by Annie Curtis, Mariana Patricia Cervantes Silva, George Timmons and Cathy Wyse. The theme of our activity was on the body clock and immune function. We discussed with the students why they get jet lag and what that has to do with their body clock. Students then moved to the first station where they got a chance to add colouring to macrophages, so we had red, yellow, blue and green macrophages and were able to look at their coloured macrophages under a microscope. Then they moved to the next station where they got to see the master clock which resides in the hypothalamus of the brain under a microscope. Finally, we displayed some images of activated macrophages and explained their function.
Cancer Cell Biology
Our workstation lead by Sudipto Das, Gillian Moore and Stephanie Annett, focused on showcasing the various laboratory-based approaches applied regularly to identify and investigate novel gene or protein-based biomarkers of cancer progression. Within our workstation, we highlighted three key areas including how samples following biopsy from a cancer patient are used to construct tissue microarrays which are used for assessing the importance of a certain protein in cancer. This was followed by demonstrating a particular tissue culture-based method used to study anti-cancer properties of drugs and finally displaying an array of microscopic images of blood vessels developing in a given tumour.
Our workstation was led by Claire McCoy, Remsha Afzal and Conor Duffy. The research focus at our lab safari station was Multiple Sclerosis (MS). We explained how the causes of MS are unknown, but that it is characterised by an influx of immune cells into the brain and spinal cord. Our research aims to investigate one type of immune cell called the macrophage. We aim to understand the damage macrophages cause in MS and if we can reverse this to provide an alternative tool for MS therapeutics. We really enjoyed explaining our research at the Lab Safari, where we showed students how MS impacts on brain function and showed them examples of activated macrophages under the microscope.
Our workstation was led by Dermot Cox and Padraig Norton. Students were given a brief history of drug discovery. Then they were introduced to the basic concepts of how a drug binds to its target and the different ways in which a drug can bind. Students were then shown a demonstration of molecular docking on a computer whereby a small molecule, or drug candidate, was virtually docked into a target binding site using the software.
The event was led by Dr Maria Morgan, Anne Grady, Prof. Tracy Robson, Dr Olga Piskareva and John O’Brien. Guides on the evening included Olwen Foley, Camille Hurley, Mary Ledwith, Seamus McDonald and Shane O’Grady.
I have recently arrived as a Postdoctoral Researcher in Dr Claire McCoys Lab in the Molecular and Cellular Therapeutics Department (MCT) at RSCI. I specialise in immune signalling pathways and inflammatory complexes underlying infectious and inflammatory diseases, including multiple sclerosis (MS), sepsis and highly virulent strains of influenza.
After obtaining my BSc in Biotechnology in 2005 from Dublin City University I was awarded a postgraduate scholarship from the Irish Research Council and went on to complete my PhD in Immunology in 2009 (DCU). I conducted my postdoctoral training in innate immune signalling with Prof Luke O’Neill in Trinity College Dublin with a strong focus on understanding the mechanisms regulating a key inflammatory complex in immune cells known as the inflammasome.
I am excited to be joining MCT and the McCoy Lab. Like Claire, I have a passionate interest in medical research and chose to work in inflammation because it has a central role in the progression of a broad range of diseases. I am also passionate about community engagement, science communication and educating the next generation about the importance of medical research and the role of inflammation in disease.
Dr Rebecca Coll is a Research-Industry Fellow at the University of Queensland, studying innate immunity and novel anti-inflammatory drugs. Rebecca received her PhD in Immunology in 2013 under the supervision of Professor Luke O’Neill at Trinity College Dublin and moved to Associate Professor Kate Schroder’s group at the Institute for Molecular Bioscience in UQ in 2014. Over the last five years, her research has focused on inflammasomes – protein complexes at the heart of inflammation and disease – and how these complexes can be targeted therapeutically to prevent damaging inflammation.
Rebecca led the biological characterisation of MCC950, a small molecule inhibitor of the NLRP3 inflammasome and an exciting prospect as a new therapy for treating patients with NLRP3-mediated diseases. In 2016, Rebecca received the Research Australia Discovery Award for her work on MCC950.
I have recently arrived as a Lecturer in Biochemistry/Immunology within the Molecular and Cellular Therapeutics Department at RSCI. I am a dedicated and passionate Biochemist/Immunologist who obtained a BA (Mod) in Biochemistry from Trinity College Dublin in 2001.
In 2006, I completed my PhD at the University of Dundee, Scotland after which I conducted my postdoctoral training in innate immunology with Prof Luke O’Neill. In 2010, I received a Marie Curie Mobility Fellowship where I gained scientific independence and re-located to the Hudson Institute of Medical Research in Melbourne, Australia. In 2014, I was awarded an Australian NHMRC project grant enabling me to lead an independent research team, conducting my research specifically on the regulation of microRNAs in innate immune cells, with a particular focus on inflammatory diseases such as Multiple Sclerosis.
My lab aims to understand how microRNAs regulate inflammation in disease. Our particular focus is how the pro-inflammatory microRNA, miR-155, plays a fundamental role in one immune cell subset called the macrophage. Macrophages are the sentinel cells of our immune system and quickly respond to infection to clear invading microbes. However, in chronic inflammatory diseases and autoimmunity, the presence of macrophages largely contributes to the damage, tissue destruction and symptoms associated with these diseases. Our research has shown that miR-155 is a key driver of this response. My lab aims to identify the molecular and functional mechanisms that underpin inflammatory macrophages, with the aim that miR-155 inhibition will lead to real therapeutic potential.
Multiple Sclerosis (MS) is a progressive degenerative disease where the prevalence in Ireland far exceeds the global average. Disease onset occurs between 20-40 years, an age critically affecting working and family life. To this day, there is no known cause and no cure for MS. Although, the early disease can be managed by current drug therapies, there is no treatment at the later progressive stages of disease, and no known treatments to repair the damage caused to the central nervous system. My research aims to uncover the role of macrophages in MS, and the contribution of miR-155 in this effect.
Claire McCoy is the recipient of a prestigious Marie Curie International fellowship and an Investigator Project Grant from the National Health and Medical Research Council (NHMRC), Australia. Altogether my research has attracted €800K in both national and international funding. I have published >21 highly cited and seminal publications in Nature Reviews Immunology, Nucleic Acids Research, Journal of Leukocyte Biology and Journal of Biological Chemistry. I am book editor for Springer Science, USA, as well as peer reviewer for international journals and funding agencies.
I will be talking about my research at 12pm TR4, Monday 13th Feb. The title of my talk will be ‘miR-155, a master regulator of the immune response’.
Dr. Claire McCoy
Lecturer in Biochemistry/Immunology,
Royal College of Surgeons in Ireland,
123 St Stephens Green,