Imagine playing Marco Polo on the big football pitch?

Do you remember playing Marco Polo and trying to acoustically locate and tag the players? Imagine playing Marco Polo on the big football pitch when each player has their eyes closed and trying to locate a football. You would probably visualise the pitch in your head and try to create a virtual reality.
What if none of the players ever saw the pitch? Football? How could it be possible to play? Is it possible at all? I have never thought of that until recently. But, there are enthusiasts around who make the difference for blind people and let them enjoy football and the game. We are lucky to know one of them! It is our John O’Brien.

John has started the football coaching journey recently. He and Stephen Bolger (of our security team at Bilfinger) have been coaching the Irish National Blind Football team and are enrolled on the FAI (Football Association of Ireland) Coach Education Pathway. Under Stephen and John’s guidance, along with their fellow coaches, Ireland put in some great performances in the tournament and finished in sixth place – a great achievement for their first international tournament.

Adapted from the news by the RCSI Communication Department

Head of the MCT Department, Prof Tracy Robson says “It seems that as well as skilfully managing our MCT laboratories, John clearly has other hidden talents. It’s amazing that John is giving up his free time to coach the Irish National Football Team; a wonderful outreach activity. We are all very proud of you John…..”

You do not need to be millennials to create the world where everyone has a sense of purpose.

Come and ask John how he does it and what is next!

Olga Piskareva

Extending international collaboration: ‘the future is East’

 

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.

At the Monument to the laboratory mouse, a sculpture in front of the Institute of Cytology and Genetics of the Russian Academy of Sciences, to commemorate the use of mice in genetic research to understand mechanisms of disease and develop new drugs

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.

During a research seminar at the Institute of Physiology and Fundamental Medicine

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’.

John Waddington   

Dr Annie Curtis wins L’Oréal-UNESCO Fellowship For Women in Science

Our congratulations to Dr Annie Curtis with L’Oréal-UNESCO Fellowship For Women in Science Award! Well done!

She was awarded a prestigious L’Oréal-UNESCO For Women in Science 2017 Fellowship at a ceremony held at the Royal Society in London on May 5th.

She was one of five winners of these fellowships and the only Irish winner this year. The fellowship will support her research into understanding the precise mechanisms by which the body clock restrains inflammation from a key immune cell called the macrophage.

Professor Tracy Robson said: “This is a fantastic achievement and I am proud to congratulate Dr Annie Curtis on this highly competitive award for which there were nearly 300 applicants. It is a great testament to her research within the recently established Immuno-Clock Lab. Annie will be an excellent ambassador for Women in Science and this award reflects the world-class research ongoing at RCSI. Indeed the only Irish winners of these For Women in Science fellowships now reside within this institution.”

Recipients of L’Oréal-UNESCO For Women in Science 2017 Fellowship. Courtesy of RCSI Communications Department

The recipients of L’Oréal-UNESCO For Women in Science 2017 Fellowship:

  • Dr Annie Curtis, Royal College of Surgeons in Ireland, the human body clock and inflammation
  • Dr Radha Boya, University of Manchester, Nanoscience
  • Dr Manju Kurian, UCL Great Ormond Street, Neurology
  • Dr Bethan Psaila, University of Oxford, Haematology
  • Dr Priya Subramanian, University of Leeds, Mathematics

RCSI Communications Department

 

Teasing out the mechanisms of biofilm formation for the treatment of S. aureus infections on indwelling devices: the role of the surface protein SdrC

Antibiotic resistance has become a great challenge in the healthcare setting. In particular antibiotic resistant strains of Staphylococcus aureus pose further challenges. Methicillin resistant S. aureus (MRSA) is widespread in healthcare facilities and in the wider community and multi-drug resistant strains have been identified. S. aureus is normally present on the surface of the skin where it causes no harm. However, it can easily colonize open wounds causing infection. Systemic infections can result from these wound infections leading to severe problems such as sepsis and infective endocarditis. Infection after surgical implantation of devices, such as joint replacements, can result in the formation of biofilms coating the devices that are difficult to treat. Biofilms are an accumulation of bacteria on a surface which often persist as most antibiotics do not easily penetrate them. In biofilms, bacteria interact directly with the foreign surface, with host proteins coating the surface and can also accumulate through interactions directly with each other.

Thus, there are multiple mechanisms involved in biofilm formation. It is important to fully understand all the mechanisms of biofilm formation in order to be able to disrupt their formation and persistence. In our recent paper, we have characterized the direct binding interaction (cell-cell adhesion) through the S. aureus surface protein, serine-aspartate repeat protein C (SdrC). Our study also reveals the mechanism of interaction between SdrC and inert surfaces. Furthermore, we have demonstrated how a small peptide can be used to block these interactions preventing biofilm formation suggesting a possible approach that could be used to treat SdrC dependent S. aureus biofilms. This study is the result of a multi-disciplinary collaboration across research institutes in Ireland and Belgium with Dr. Brennan (RCSI) contributing to the molecular modelling, Prof. Joan Geoghegan, Prof. Timothy Foster and Leanne Hayes (Trinity College Dublin) leading the molecular biology and microbiological functional studies and researchers from University Catholique de Louvain characterizing the interactions quantitatively using atomic force microscopy.

Marian Brennan

More details can be found in “Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC”.

 

Decoding neuroblastoma microenvironment

MCT Research Talks – 24th April 2017

The main challenge in treating high-risk neuroblastoma is to combat tumour metastasis and development of resistance to multiple chemotherapeutic drugs. In the native tissue, cancer cells are surrounded by a three-dimensional (3D) microenvironment which provides biological and physical support and determines disease initiation, progression, patient prognosis and response to treatment. The conventional two-dimensional (2D) cell culture lacks this feature resulting in discrepancies between in vitro and in vivo results. Current neuroblastoma studies employ either 2D cell culture systems or murine models or alternatively a mix of both.

In collaboration with Dr Caroline Curtin and Prof Fergal O’Biren (TERG), we decided to bridge the gap between 2D culture and in vivo tumours in neuroblastoma research by developing a tissue-engineered cell culture model of neuroblastoma. This project is supported by a pilot grant from Neuroblastoma UK.

To understand what signalling pathways are activated in 2D, 3D and in vivo neuroblastoma models, we decided to look closer at the differences between conventional 2D neuroblastoma cells and their xenografts. This way we hope to find those targets that are activated in both tumour microenvironment and the 3D tissue engineered models. Ciara and Larissa have begun this search by profiling xenograft samples with a panel of antibodies. Ciara became particularly fascinated by the elevated levels of c-jun, TCF1 and LEF1 in cisplatin-resistant neuroblastoma xenografts suggesting that the development of cisplatin resistance in neuroblastoma may be accompanied by activation of the wnt/b-catenin pathway in vivo. Larissa identified that cisplatin-resistant neuroblastoma cells secrete chromogranin A (CgA) at levels higher that cisplatin-sensitive cells. CgA levels also correlated with increased vascularisation and volume of murine orthotopic neuroblastoma xenografts. Altogether it suggests that CgA can be used as a marker of neuroblastoma cell growth both in vitro and in vivo.

Olga Piskareva

Characterisation of Novel FCγRIIa Inhibitors

MCT Research Talks – 10th, April 2017

Research talks were presented by Sheila Zarros, Tatyana Devine, Afnan Ali and Padraig Norton. Tatyana and Sheila were talking about challenges in the characterisation of novel FCγRIIa inhibitors.

Fc receptors are a widely distributed family of receptors that mediate cellular responses to antibodies or immunoglobulins (Ig). The Fc gamma receptor II, FcgRII (also known as CD32) is a low-affinity receptor for Fc portion of immunoglobulin G (IgG) and has two isoforms FcgRIIa and b. Fcg RIIa is widely expressed by human innate immune cells and is the only Fc gamma receptor found on human platelets.

Our group and others have demonstrated the significance of this receptor in the activation of platelets by bacteria, suggesting that it could be an important target in the treatment of sepsis. Its implications in rheumatoid arthritis, cancer pathogenesis, allergic reactions and flu virus-induced thrombocytopenia were also demonstrated.

Our project is focused on characterisation of novel small molecule compounds designed for targeting FcgRIIa receptor’s IgG binding site to inhibit bacteria-induced platelet aggregation in primary human plasma and investigation of their interactions with the FcgRIIa using surface plasmon resonance technology.

Afnan Ali reported on the role of the Fc gamma Receptor IIa (FcγRIIa) in platelet activation. Platelets express the FcγRIIa and this receptor has been identified as a key receptor in bacterial activation of platelets leading to thrombocytopenia and platelet activation. The aim of this study was to identify drugs that could be re-purposed for the treatment of sepsis and immune-mediated thrombocytopenia. We identified 42 drugs predicted to inhibit binding of IgG1 to the FcγRIIa using virtual high throughput screening. This included 20 antibacterial agents, 3 anti-fungals, 3 antiviral agents, 7 antineoplastics and 3 immunosuppressives. A selection of drugs were tested for inhibition of platelet adhesion to IgG, S. aureus-induced platelet aggregation and assessed for platelet activation. This work has identified multiple drugs that have potential to be to be repositioned for thrombocytopenia, sepsis and autoimmune disorders, as well as providing a possible mechanism of action to explain the immunosuppressive effects of some anti-neoplastics and immunosuppressive drugs.

Japan Society for Promotion of Science – Short-term post-doctoral fellowship

Following a workshop conducted at Hoshi University, Tokyo, Japan organized through the ISCA-Japan initiative funded by SFI in October, 2015 a successful collaborative initiative was established between Dr. Sudipto Das (MCT, RCSI) and Prof. Hiroko Ikeda (Department of Neurophysiology, Hoshi University) to investigate the role of epigenetic modifications like DNA methylation in driving a neuronal dysfunction phenotype associated with Diabetes mellitus (DM). Moving this collaboration forward with support from his collaborators at Hoshi University Dr. Sudipto Das has recently received a prestigious short-term post-doctoral fellowship to further his work at Hoshi University from the Japan Society for Promotion of Science (JSPS), which would essentially cover travel, subsistence and a research consumable allowance of 562,000 Japanese Yen. As a part of this fellowship, Dr. Das will travel to Japan for a period of 1.5 months in January 2018. The successful completion of the proposed project as a part of this proposal will for the first time allow the scientific community to understand as to how epigenetic modifications like DNA methylation impact on neurological dysfunction in endocrine

The successful completion of the proposed project as a part of this proposal will for the first time allow the scientific community to understand as to how epigenetic modifications like DNA methylation impact on neurological dysfunction in endocrine related disorders such as DM, thus opening up avenues to utilize this modification to potentially predict such conditions in DM patients.

Sudipto Das

The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma

Asthma is of particular relevance to the area of circadian control of immunity, since it is a disease with very strong clinical evidence demonstrating regulation by circadian variation. Airway hypersensitivity and asthma attacks are more common at night in humans. The molecular basis for this is unknown and no model of asthma in animals with genetic distortion of the molecular clock exists.

Asthma is under strong circadian variation. Asthma symptoms worsen at night, particularly in the early hours of the morning. Lung function fluctuates in healthy individuals over 24 h period and these fluctuations are even more pronounced in asthmatics.

In this study, we showed that mice lacking the main clock transcription factor BMAL1 in myeloid cells have increased lung inflammation demonstrated by higher numbers of eosinophils and increased IL-5 (key pathogenic cytokine in asthma that recruits eosinophils).This suggests that Bmal1 is a potent negative regulator, in myeloid cells in the context of allergic asthma. Our findings might explain the increase in asthma incidents during the night in humans when BMAL1 expression is low.

Dr. Zbigniew Zaslona from TCD (pictured here) was the lead author on the study. Both Dr. Annie Curtis (MCT) and Prof. Luke O’Neill (TCD) were joint senior authors on the paper.

The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma.

Zaslona Z, Case S, Early JO, Lalor SJ, McLoughlin RM, Curtis AM*, O’Neill LA* – Both authors contributed equally to this study.

Am J Physiol Lung Cell Mol Physiol. 2017 Mar 23:ajplung.00072.2017. doi: 10.1152/ajplung.00072.2017. [Epub ahead of print]

Daffodil Day Bake sale – 24/03/2017

Daffodil day is marked on the annual calendar as one of the most significant days recognised for collecting donations from the Irish public to fund cancer research as well as various services provided by the Irish Cancer Society. Given the substantial amount of cancer researchers based in RCSI and in particular in MCT, a joint effort between the MCT and the Department of Physiology and Medical Physics was carried out to organise a “Bake sale” aimed to raise funds on this occasion. Dr. Sudipto Das (MCT) and Dr. Catriona Dowling (Physiology and Medical Physics) primarily organised the bake sale.

This year bake sale boasted a wide variety of baked goods prepared by various members of the staff including senior researchers and post-graduate students. One the main highlights of the bake sale was an auction for an exquisite chocolate biscuit cake with a daffodil theme baked by Ms. Ina Woods (Physiology and Medical Physics). The auction was successfully completed by selling the cake at the highest bid of 50 euro by Prof. Jochen Prehn. This year bake sale was a highly successful event, which effectively raised 800 euro with all proceeding going towards the Irish Cancer Society.

We thank everyone who made this fundraising event into an enjoyable and fruitful event.

 Reported by Sudipto Das