MCT Research Forum – March 25th 2019 at Cheyne Lecture Theatre at 3.00pm – 4.00pm
Prof. Paul Moynagh – “New Players in Ubiquitination: Relevance to innate immunity and inflammatory diseases”
Prof. Moynagh obtained his B.A. (Mod) and PhD from Trinity College Dublin and took up a lectureship in UCD Department of Pharmacology in 1995. During his time in UCD Prof. Moynagh became Associate Professor of Immunology and held the position of founding Head of the UCD School of Biomolecular and Biomedical Science. In 2006 he joined National University of Ireland, Maynooth as Director of its Institute of Immunology and currently holds the positions of Head of Department of Biology and Director of the Human Health Research Institute at Maynooth University. Prof. Moynagh has published extensively in the area of immunology-related research and in 2009 was awarded the NUI Centennial Prize for Academic Publishing in Medical and Health Sciences. He was also awarded the 2014 Irish Area Section Biochemical Society (IASBS) medal. This medal is awarded annually to an Irish-based researcher who has made an outstanding contribution during his/her career in the broad area of Biochemistry. Prof. Moynagh’s research focuses on innate immune signalling and the identification of novel regulators of inflammatory pathways with his most recent findings revealing immunomodulatory roles for the Pellino E3 ubiquitin ligases in inflammasome activation (Humphries et al; Nature Communications (2018), antiviral immunity (Siednienko et al; Nature Immunology (2012)), controlling intestinal homeostasis (Yang et al; Nature Immunology (2013)) and regulating insulin resistance (Yang et al; Immunity (2014)). He has generated >€10M of independent research funding and has directed a number of major research initiatives including the coordination of European Commission-funded research programmes. Prof. Moynagh has also played a leading role in the training of PhD students and directed 2 large structured PhD programmes
Dr. Stephanie Annett –“Unravelling the role of FKBPL in obesity”
Dr. Jennifer Dowling – “The Inflammasome: a novel therapeutic target of Hypoxic Brain Injury in Neonates”
Tea/Coffee and Cookies sponsored by
Prof Luke O’Neill delivered the inaugural lecture at the RCSI Research Seminar Series yesterday. Luke O’Neill is the professor of Biochemistry and Immunology at Trinity College Dublin. Luke is a world-renowned scientist known for his contributions to the field of Immunology, more specifically Toll-like receptors, innate immune signaling, cytokines and most recently Immunometabolism. He is one of Ireland’s most influential scientists having published >300 publications and is in the top 1% of the world’s most cited scientists in Immunology. He is the recipient of many prestigious awards including the Boyle Medal for Scientific Excellence and last year was elected a Fellow of the Royal Society.
Luke told us many exciting stories. The first highlighted how the inflammasome sensor NLRP3 is critical for the production of the pro-inflammatory cytokine IL-1. A cytokine essential for our fight against infection, but is elevated and extremely damaging in many diseases including Rheumatoid arthritis, colitis, Parkinson’s, Alzheimer’s, diabetes and hypertension. Luke’s team discovered a small molecule inhibitor against NLRP3 that has shown efficacy in 32 models of disease, as astounding effect never observed before. The inhibitor is now entering clinical trials and could excitingly pave the way as a radical treatment for many diseases.
The second story introduced the concept of Immunometabolism, a phenomenon where immune cells utilize metabolic pathways to generate inflammatory mediators. In response to infection, immune cells such as macrophages increase the production of glycolysis whilst at the same time cause a block in Kreb’s cycle. This block leads to the accumulation of intermediates such as succinate. Importantly, Luke has shown that succinate is critical for the production of IL-1 via the transcription factor HIF-1alpha. Inhibition of succinate ablates IL-1 production in response to infection, as well as in a number of disease models tested. Luke highlights that the manipulation of energy pathways could very likely provide an alternative mechanism for therapy in inflammatory disorders.
It was a real pleasure to hear Luke speak at RCSI. To learn more about the above stories, check out the following publications:
- Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O’Neill LA. (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine. 21(3):248-55
- Tannahill GM, Adamik J, Goel G, Curtis AM, Palsson-McDermott EM, Masters SL, McGettrick AF, Bernard NJ, Jany SS, Corr SC, Gardet A, Clish C, Zheng L, Beasley FC, Cummins E, Taylor CT, Frezza C, Gottlieb E, Kelly V, Auron PE, Xavier RJ and O’Neill LA (2013) Succinate is a danger signal from mitochondria that induces IL-1beta transcription via HIF1alpha. Nature 496(7444):238-42
Written by Claire McCoy