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:
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.
While RCSI is an institution with a long-standing international perspective on education in the health sciences, it has as a strategic goal the further extension of its international activities, particularly in relation to research collaborations. RCSI is doing so through several mechanisms, which include Science Foundation Ireland International Strategic Collaboration Awards (ISCAs), namely ISCA-Brazil, ISCA-China and ISCA-Japan, awards from the Japan Society for the Promotion of Science (JSPS), the EU Erasmus+ programme, and via joint programmes with individual institutions. Over the past several years, I’ve been pleased to contribute to these developments and continue to do so in my new role as Professor Emeritus.
In October-November 2016, I spent three weeks in Japan under a JSPS Invitation Fellowship. From a base at Hoshi Pharmaceutical University, Tokyo, I also visited and gave seminars at Nihon University at its Tokyo and Matsudo campuses, Nagoya University, and Takeda Pharmaceutical Company, Fujisawa. Even after many previous visits to Japan, it’s difficult to describe the enduring professional and personal pleasures of interacting and fostering collaborations with Japanese academics/scientists and enjoying their beautiful country and so hospitable a culture and society. In addition to ongoing research collaborations with Prof. Hiroko Ikeda and her colleagues, this summer will see the second exchange of RCSI and Hoshi University students to participate in the International Research Summer School, directed in RCSI by Dr. Sarah O’Neill (MCT), whereby up to four students from each Institution travel to the other to undertake a 2-month research project. Additionally, later this year Dr. Sudipto Das (MCT) will travel to Hoshi University under a JSPS Postdoctoral Fellowship to further extend collaborative research studies. We hope that such interactions will grow over the years to come.
In February-March 2017, I spent three weeks in China under a joint appointment as a Professor of Pharmacology in the College of Pharmaceutical Sciences at Soochow University, approximately 100 km west of Shanghai. China is a country that is now pursuing a ‘twin-track’ approach of “… internal restructuring of its economy combined with exposure to global trade winds and investment”. While this presents some similarities but many fascinating contrasts with academe in both Japan and Ireland, interacting and fostering collaborations with Chinese academics/scientists also brings many professional and personal pleasures. While there, I gave three undergraduate lectures on mental health, met with postgraduate students and postdoctoral researchers, and facilitated the visits of Prof. Tracy Robson & Dr. Darran O’Connor (MCT), Prof. Jochen Prehn (Physiology & Medical Physics) and Prof. Brian Kirby (School of Pharmacy) to Soochow University and the subsequent reciprocal visits of Profs. Xinliang Mao and Xinchen Teng to RCSI. In addition to ongoing research collaborations with Prof. Xuechu Zhen, this summer will see the third exchange of RCSI and Soochow University students to participate in the International Research Summer School, whereby, as with Hoshi University, up to four students from each Institution travel to the other to undertake a 2-month research project. Dr. Darren Griffith (Pharmaceutical & Medicinal Chemistry) will be the next RCSI colleague to visit Soochow University and we hope that such interactions, like those with Hoshi University, will grow over the years to come.
It is difficult to think of a greater contrast than my recent visit, April 2017 under Erasmus+ funding, to Novosibirsk State University and the Institute of Physiology and Fundamental Medicine. Novosibirsk is Russia’s third-largest city and is located in Siberia, approximately 2,800 km east of Moscow. The University and Research Institutes are located in Akademgorodok [Akadem = academic, gorod = town, ok = small, hence Akademgorodok = small academic town], the purpose-built educational and scientific centre of Siberia constructed in the late 1950s approximately 30 km south of the city of Novosibirsk. In April, there was still some snow on the ground and the nearby Ob river was still frozen and will remain so until the end of May. During my stay there, the weather ranged from one blizzard and one (in their terms) ‘regular’ fall of snow through to warm, sunny periods with a temperature of 20C; Prof. Marc Devocelle (Pharmaceutical & Medicinal Chemistry) and I were reluctant to travel to Novosibirsk until April, to avoid the harsh Siberian winter, a meteorological objective that was only partially successful. This academic centre has both original and new buildings, with good teaching and research facilities. Under the kind offices of Profs. Vladimir Pustylnyaki and Michele Debrenne, Novosibirsk State University, I gave three undergraduate lectures on the neuroscience of mental health, and under the auspices of Dr. Tatiana Lipina, Institute of Physiology and Fundamental Medicine gave a postgraduate seminar.
Meetings with them and several other colleagues explored the potential for future research collaborations. After what we regarded as a good meeting, one colleague reached into a cupboard for a bottle of vodka and poured us each a generous measure; he hoped this would induce ’emotional warmth’ commensurate with what he regarded as the positivity of the meeting. After this had been imbibed, he then poured a second generous measure of vodka, to reinforce these positive sentiments. Clearly, RCSI needs to reconsider its policies in this regard with a view to appropriately realigning its practices to these new international standards. As I write this in the second week of May, Prof. Konstantin Volcho, Dr. Ekaterina Semenova and Dr. Artyom Rogachev are currently making reciprocal visits to RCSI under Erasmus+ funding and we hope that such interactions, like those with Hoshi and Soochow Universities, will grow over the years to come.
To paraphrase: ‘The future is bright, the future is East’.
Irish Association for Cancer Research – Annual Meeting takes place at Newpark Hotel, Kilkenny on Thursday 23 and Friday 24 February 2017.
MCT cancer researchers secured oral presentations at different sessions. Prof Ray Stallings is a guest speaker at the Plenary Session focused on challenges in childhood cancers. He will be discussing ‘Modulation of neuroblastoma phenotype with epigenetically regulated miRNAs’.
Stephanie Annett will be giving a talk ‘FKBPL as a novel prognostic biomarker and therapeutic agent in high-grade serous ovarian cancer’ at Proffered Paper Session on Thursday morning. Two Irish Cancer Society funded PhD students will be discussing their findings at the Irish Cancer Society Scholar and Fellow Presentation session. Louise Walsh – ‘RNA sequencing identifies bromodomain proteins as a therapeutic strategy for invasive lobular carcinoma’ and Brian Mooney – ‘Expression of the cocaine- and amphetamine-regulated transcript recruits BAF chromatin remodelling complexes to the estrogen receptor’.
Dr Campbell aims to elucidate and address questions associated with dysfunctional vasculature within neural tissues. Recently published in Nature Medicine, Dr Campbell made a significant discovery uncovering the role of the NLRP3 inflammasome in the development of one of the most common forms of central retinal blindness, AMD. His lab is now pursuing a range of novel therapeutic solutions for the treatment of AMD and recently reported on the translational potential of human IL-18 as an immunotherapy.
Dr Campbell interests also focus on the blood-brain barrier, where he recently reported for the first time on the auto-regulated diffusion of amyloid-β in Alzheimer’s disease. More recently, he has identified molecular mechanisms underlying the development of chronic traumatic encephalopathy (CTE) to concussive injuries in athletes and military personnel. He spearheads a project involving the use of RNA interference (RNAi) to modulate levels of distinct tight junction proteins at the blood-brain barrier. This led to a novel form of patented technology that was termed “Neural Barrier Modulation” which could have broad applications for a range of neurological conditions.
Dr Campbell is the recipient of Ireland’s most prestigious prize for young researchers, the “President of Ireland Young Researcher Award (PIYRA)“, in addition to the international Genentech/ARVO fellowship. He will be speaking today on ‘the cerebrovascular nature of neurological disorders’ at 12 pm in Tutorial Room 2/3. Lunch will be provided for all after the talk.
Written by Dr Claire McCoy, Lecturer in Biochemistry, MCT, RCSI.