MOLECULAR AND CELLULAR MECHANISMS UNDERLYING INFLAMMATORY PROCESSES PhD Programme in Molecular and Cellular Mechanisms underlying inflammatory processes TABLE OF CONTENTS 7TH AUGUST 2014 TCD Oral Presentations IFN-γ production by Natural Killer Cells induces TCD M1 macrophage activation and upregulates VLA-4 The role of metabolism and hypoxia in the regulation of expression on CD4+ T cells in experimental autoimmune human T cell subsets encephalomyelitis D. Cluxton, K.H.G. Mills, J.M. Fletcher - - - - - - - - - - - 1 N.C. Mc Guinness, L.S. Dungan, M.A. Lynch, K.H.G. Mills - - - - 9 UCC NUIG IGF-1R signalling is essential for mitochondrial Modelling ATR disease-related mutations using chicken maintenance and function DT40 cells A. Lyons, R. O’ Connor - - - - - - - - - - - - - - - - 2 M. Llorens Agost,- J.K. Eykelenboom, N.F. Lowndes - - - - 10- UCD UCC CX3CL1 plays a role in memory-associated synaptic Altered regulation of adipogenesis in disease processes plasticity in the rat hippocampus S. Davies, T. McCarthy - - - - - - - - - - - - - - 11- - A. Wdowicz, G.K. Sheridan, D.J. O’Connell, K.J. Murphy - - - 3- TCD TCD Noradrenaline-mediated protection against Functional analysis of nucleic acid sensors in the TNF-α-induced neuronal atrophy CNS - Implications for infection, brain injury and E. O’Neill, A. Harkin, V.A. Campbell, T.J. Connor - - - - - 12- - neurodegeneration D. Cox, A.G. Bowie, M.A. Lynch, C. Cunningham, A. Dunne - - -4 UCD Regulation of the human Prostacyclin receptor gene NUIG within the cardiovascular system: Influence of gender Regulatory T-cells of mouse display distinctive surface specific hormones glycosylation patterns that correlate with their S.B. Eivers, B.T. Kinsella - - - - - - - - - - - - - 13- - suppressive function J. Cabral, S. Hanley, J. Gerlach, L. Joshi, T. Ritter, R. Ceredig, M.D. NUIG Griffin - - - - - - - - - - - - - - - - - - - 5- -Nucleosome - organisation of the vertebrate centromere UCC J.G.W. McCarter, K.F. Sullivan - - - - - - - - - - - 14- - Cytotoxic effects of UPEC on human macrophage TCD I. O’Neill, D. Clarke - - - - - - - - - - - - - - - - - - 6 Modulation of the endocannabinoid system and PanX1- mediated neuroinflammation in an in vitro model of TCD Alzheimer’s Disease Comparative bioenergetics in parental sensitive and Cisplatin resistant cancer cell subline S.G. Fagan, V.A. Campbell - - - - - - - - - - - - - - - - - - - - - 15 F. Geoghegan, E. O’Connor, K. Grankvist, T. Nilsson, P.B. Motlagh, R.K. Porter - - - - - - - - - - - - - - - - - - 7- - - UCD Poster Presentations Serotonin transporter regulation in an animal model TCD of Rheumatoid Arthritis – Toward understanding S1P receptor activation attenuates psychosine-induced depression in Chronic Inflammatory Diseases astrocyte cell death E. Brown, J. Haase - - - - - - - - - - - - - - - - 8 - - C. O’Sullivan, K.K. Dev - - - - - - - - - - - - - - - - - 16 PRTLI Programme PhD PHD PROGRAMME IN MOLECULAR CELL BIOLOGY MOLECULAR AND CELLULAR MECHANISMS UNDERLYING INFLAMMATORY PROCESSES Phd Programme in The role of metabolism and hypoxia in the Molecular and Cellular Mechanisms regulation of human T cell subsets underlying inflammatory processes TCD TABLE OF CONTENTS D. Cluxton, K.H.G. Mills, J.M. Fletcher cont. 7TH AUGUST 2014 ORAL UCC UCD h17 cells are important pathogenic effector cells in Treg cells. Glucose uptake was evaluated via culture Use of Lacticin 3147 and essential oils against food- Quantitative analysis of IL-17 induced protein expression in autoimmune diseases such as rheumatoid with a fluorescent glucose analog (2 - NBDG). It was borne pathogens profiles of Psoriatic Arthritis B cell models arthritis (RA) and multiple sclerosis (MS). shown that Th17 -lineage cells expressed increased A. Campion, D. Field, P.D Cotter, C. Hill, R.P. Ross - - - - - - - 17 M. Doyle, S. Pennington - - - - - - - - - - - - - - - - 27 TOn the other hand, regulatory T (Treg) cells play a 2 -NBDG compared to CD4+CD161 - T cells. This suggests UCD TCD crucial role in maintaining tolerance and preventing that Th17 cells utilise glycolysis while Treg cells employ The role of the bone morphogenetic antagonist Gremlin mTORC1 regulation of Dendritic cell metabolism through autoimmunity. Under healthy conditions there is a the aerobic process of oxidative phosphorylation for in the pathogenesis of Chronic Lung Disease HIF1α and iNOS balance between Treg and effector T cell responses energy supply and consumption. J. Cornwell, P. McLoughlin - - - - - - - - - - - - 18 - - S. Lawless, D. Finlay - - - - - - - - - - - - - - -28 - - which may be perturbed in autoimmunity. Therefore, This switch towards anaerobic glycolysis could TCD it is crucial to understand the factors that regulate this promote Th17 cell survival within inflamed tissues, Cytokine release inhibitor drug, CRID3, inhibits the balance. Recently, a role for metabolism in murine T cell NLRP3 inflammasome in glia Abstracts (in absentia) where oxygen supply is limited. Hypoxia inducible factor differentiation has been identified. C.N. Dempsey, R.C. Coll, A.A.B. Robertson, M.A. Cooper, L.A.J. TCD 1 α (HIF -1α), which is a transcription factor best known O’Neill, M.A. Lynch - - - - - - - - - - - - - - 19- - - The effect of inflammatory caspases in Colitis and CD4+ T cells were sorted from PBMC using magnetic for orchestrating the cellular response to hypoxia, now NUIG Colorectal Cancer beads and further sorted via the MoFlo sorter into the also appears to be an important factor in regulating B. Flood, K. Oficjalska, E. Creagh - - - - - - - - - - 29- - Examination of the inner centromere compartment in a CD161+, CD161 - and Treg cell populations. The metabolic metabolism and T cell differentiation. The data showed mammal UCD profile of each T cell population was determined via the that Th17 cells express increased levels of HIF -1α via T. Masterson, K. Sullivan - - - - - - - - - - - - - - - - 20 Structure-based drug design for NADPH Oxidases Seahorse XF Analyzer. CD4+ T cells expressing the human flow cytometric analysis. UCC S. O’Neill, U. Knaus - - - - - - - - - - - - - - 30- - - Th17 cell marker CD161 were found to have increased Screening protein Kinase mutants to identify novel In conclusion, the data suggests that Th17 lineage glycolysis compared with CD4+CD161 - cells. We genes required for biofilm formation inCandida Albicans TCD cells employ glycolysis for their energy supply, Combretastatin (CA)-4 and its novel analogue CA-432 confirmed this by investigating the effect of inhibiting N. Konstantinidou, F. O’Gara, J. Morrissey - - - - - - - 21- - orchestrated by the increased expression of HIF -1α, and impair T-cell migration through the Rho/ROCK signalling glycolysis following treatment with 2 -deoxy -D -glucose pathway have the potential to persevere within inflamed tissues. TCD (2 -DG) and rapamycin on CD4+ T cell growth, revealing The PYHIN protein MNDA is involved in the regulation of J. Pollock, D. Zisterer - - - - - - - - - - - - - - 31 - - a decrease in Th17 cell expansion and a parallel increase interferon alpha expression NUIG D. Casserly, S. Carpenter, K.A. Fitzgerald, A.G. Bowie - - - -22 - Identification of new sugar binding bacterial adhesins UCD encoded by the human gut metagenome Exploring the immune modulatory role of MPB70 and C. Agbavwe, C. O’Byrne, A. Boyd, Lo. Joshi - - - - - - - - - 32 MPB83 by Mycobacterium tuberculosis TCD L. Carr, C. Brereton, E. Lavelle, S. Gordon - - - - - - - - 23- - The anti-inflammatory actions of noradrenergic agents UCC as a target to prevent neurodegeneration in Parkinson’s The effect of Isoellipticines on Leukaemia cells disease E.G. Russell, T.G. Cotter - - - - - - - - - - - - - 24- - J.D.Yssel, T.J. Connor, A. Harkin - - - - - - - - - - - 33- - TCD TCD γβ T cells, a novel T cell subset with a pathogenic role in Double stranded RNAs of different lengths have Il-17-mediated CNS autoimmunity divergent effects on innate immune activation in the periphery and the brain Th17 cells have the ability to survive and S.C. Edwards, K.H.G. Mills - - - - - - - - - - - - - 25 - - expand within inflamed environments, N. McGarry, K. Mitchell, C. Cunningham - - - - - - - - 34- - such as those found in rheumatic joints, NUIG due to their utilization of glycolysis Investigation into the regulation of p75NTR by NGF, and and increased expression of HIF-1α, its pro-survival signaling in breast cancer cells whereas Treg cells utilise oxidative R. Chakravarthy, J. Hillis, A. Gorman - - - - - - - - - 26 - - phosphorylation for their metabolism. Hypoxia and metabolism may be targeted to maintain a balance between pro and PRTLI Programme PhD anti-inflammatory T cells. PRTLI Programme PhD 1 PHD PROGRAMME IN MOLECULAR CELL BIOLOGY MOLECULAR AND CELLULAR MECHANISMS UNDERLYING INFLAMMATORY PROCESSES IGF-1R signalling is essential for mitochondrial CX3CL1 plays a role in memory-associated synaptic maintenance and function plasticity in the rat hippocampus UCC UCD A. Lyons, R. O’ Connor A. Wdowicz, G.K. Sheridan, D.J. O’Connell, K.J. Murphy ORAL ORAL ancer cells exhibit increased glycolytic rates and [1] Favre, C., et al. (2010). “Mitochondrial pyrimidine nucleotide carrier number of cytokines and chemokines act plasticity. Finally, we confirm that CX3CL1 activates glucose transport to facilitate adaptation to (PNC1) regulates mitochondrial biogenesis and the invasive as regulators of cognitive function under second messenger signalling molecules such as Akt in a phenotype of cancer cells.” Oncogene 29(27): 3964 -3976. the high energy demand imposed by increased