Multiple Sclerosis Research Network – 30th May 2018

In honour of World MS Day on the 30 May 2018; the Molecular and Cellular Department in the Royal College of Surgeons Ireland along with Trinity College Dublin, MS Society Ireland and Novartis have joined together to create an MS Research Network event.

The event will comprise of three parts; the first is a World MS Day Fundraiser located in the main foyer of RCSI between 8.30 – 10 am, please come and support the #bringinguscloser campaign. The second is a Researcher Forum for scientists working on MS in Ireland, with the aim to establish an official researcher network to enhance collaboration, visibility, and congeniality. The third is a Public Event to launch the most recent MS Society report and inform the public of the importance and relevance of MS research that is conducted in Ireland.

All are welcome to these events (see below details). To register for the day event, email Harriet Doig at harrietd@ms-society.ie, to register for the evening event, email Emma Kinnane at emma.kinnane@novartis.com.

Written and organised by Claire McCoy

World MS Day Fundraiser – Royal College of Surgeons, Main Foyer. 8.30 – 10am

Researcher Forum – Royal College of Surgeons in Ireland, Tutorial Room 2/3
12.00 Meet and Greet (lunch is provided)
12.30 Harriet Doig (MS Society Ireland). ‘The value of a research network in Ireland’
12.40 Claire McCoy (RCSI). ‘The importance of microRNA-155 in Multiple Sclerosis and my contribution to an MS research network’
13.10 Eric Downer (Trinity College Dublin). ‘Exploring Exercise & Cannabinoids as Therapeutic Targets in MS’
13.40 Una Fitzgerald (NUIG). ‘My research and how I can contribute to an MS research network’

14.15 Tea Break

14.45 Jill Moffat (Queen’s University Belfast). ‘The Northern Ireland MS network – challenges and opportunities’
15.00 Denise Fitzgerald (Queen’s University Belfast) ‘My Research and how the Northern Ireland MS network benefits it’
15.30 Mary Fitzsimons (Beaumont Hospital). ‘How to build an MS electronic patient record, lessons from the epilepsy lighthouse project’
15.45 Alexis Donnelly (Patient advocate). ‘How patients can help build MS research’

Public Event – Trinity Biomedical Sciences Institute, Trinity College Dublin
18.00 MS Society Report Launch
18.20 Clinician – Orla Hardiman (Beaumont Hospital and Trinity College Dublin)
18.40 Researcher – Claire McCoy (RCSI)
19.00 Patient Advocate – Joan Jordan (Patient Advocate)

Development of Novel Treatments for Sepsis

MCT Research Talks

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.

Prof. Steve Kerrigan’s research team

Funded by: Science Foundation Ireland, Enterprise Ireland, Irish Research Council, British Heart Foundation, Health Research Board, Wellcome Trust

Daffodil Day Spinathon

On Friday, March 23rd, MCT and the Department of Physiology hosted a Spinathon for Daffodil Day, the Irish Cancer Society’s biggest fundraising day of the year. The aim of the Spinathon was to cycle the same distance as the Ring of Kerry, a total of 170 km on each bike. A number of willing participants took part on the day, including Sudipto, Lisa, George and Tony from MCT. A total of €1966 between the JustGiving.ie fundraising page and bucket collections on the day.

Final Year Royal College of Surgeons PhD Student Lisa Dwane from Clondalkin who is conducting research into hormone driven breast cancer with some daffodils for Daffodil Day and her colleagues (from left) Post Doctoral Researchers Dr Gillian Moore from Baldoyle and Dr. Brian Mooney from Bray Co. Wicklow and Dr. Stephanie Annett from Lisburn Co Antrim.
Pic Steve Humphreys
22nd March 2018

Well done to everyone involved!

World Haemophilia Day 2018

Haemophilia is a genetic blood disorder that affects one in 5,500 people in Ireland. This disorder impairs body’s ability to make blood clots and stop bleeding.

Last Tuesday the 17th of April was World Haemophilia Day 2018, the Irish Haemophilia Society (IHS) celebrated both World Haemophilia day and there 50th anniversary with multiple events around the country.

The day began with myself (in the middle of the pic) and Brian O’Mahony (the CEO of the IHS) appearing on Ireland AM to speak about the development of Haemophilia care in Ireland over the last 50 years.

The celebrations continued with the revealing of a street art project reflecting the personal experience of patients and nurses from St James’s Hospital. The visual, commissioned by the Irish Haemophilia Society in partnership with Roche, was developed by artist Shane O’Malley and unveiled on Machen street and in St. James’s Hospital to coincide with World Haemophilia Week.

Brian O’Mahony and Dr. Michelle Lavin spoke at the Shire office about personalised treatment as well as the challenges that still need to be addressed to further our understanding of Haemophilia.

The Day concluded with the “light it up red” light show, a long list of landmarks including RCSI, Edinburgh castle and the convention Centre were among landmarks worldwide which were lit up red for the night.

Reported by Seamus McDonald

https://www.facebook.com/irishhaemophiliasociety/

 

A new strategy to study neuroblastoma

MCT Research Talks

Neuroblastoma is a cancer of the nervous system that primarily affects children aged 5 and younger. Although neuroblastoma accounts for only 5% of childhood cancers, it is responsible for approximately 15% of childhood cancer deaths. For children with high-risk neuroblastoma – children in which cancer has spread significantly – the outlook is extremely poor. Approximately 1 in 5 of these children will not respond to treatment, and of those that do, 50% will develop drug resistance leading, in many cases, to death.

Dr Olga Piskareva, an NCRC supported scientist and Honorary Lecturer at RCSI, has recently published a study describing a new way to grow cancer cells in the lab. Traditionally, researchers grow cancer cells in the flasks on the flat surface. This is not the way cells grow in the human body. Dr Piskareva in collaboration with Dr Curtin and Prof O’Brien has designed a new way to grow cancer cells that recreate their growth in 3 dimensions as in the human or mice body. They used special cotton wool like sponges as a new home for cancer cells and populated them with cancer cells. At the next step, they gave cells the drug at the different amount and checked what happened. In this system, cells responded only to the drug at doses used in the clinic or mice models.

This new strategy to grow cells on sponges should help to understand cancer cell behaviour better and accelerate the discovery and development of new effective drugs for neuroblastoma and other cancers. This, in turn, will make the outlook for little patients better and improve their quality of life.

Dr Olga Piskareva and her research group

More details about our research can be found in Dr Piskareva’s blog!

Reported by Olga Piskareva

MCT Success at RCSI Research Day 2018

Dear All,
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.
 Well done all. A fantastic achievement for MCT.
 Best wishes,
Tracy

MCT at RCSI Research Day 2018

Five MCT researchers were selected to give oral presentations at RCSI Research Day 2018 – Wednesday 7th March

Category: Early Career Investigators (Post-doctoral Fellows):

Mariana Patricia Cervantes Silva: Those mitochondria have got rhythms! Mitochondrial activity and antigen processing in dendritic cells is dependent on the molecular clock protein BMAL1

Stephanie Annett: The role of FKBPL in LPS induced endothelial barrier dysfunction.

Category: All Postgraduates (Thesis in 3)

Rebecca L Watkin: S. aureus induced miR330-3p expression triggers abnormal permeability in an ex-vivo 2D model of sepsis.

Orla Fox: Uncoupling Activated Protein C Functions by Inhibition of PostTranslational Beta-Hydroxylation.

Edmund Gilbert: The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland

Well done!!!

President Higgins Presents SFI Future Research Leaders Award to Dr Claire McCoy

On 25th January 2018 – President of Ireland, Michael D. Higgins, honoured Dr Claire McCoy with the SFI President of Ireland Future Research Leaders Award at a special ceremony in Áras an Uachtaráin in Dublin. Claire was among one of five recipients for this prestigious award and receives a total of €1.5m, which will support a team of 4 researchers; Dr Jennifer Dowling (Senior Post-Doctoral Researcher and hon. Lecturer), Dr Elizabeth John (Research Assistant), Ms Remsha Afzal (PhD student) and Mr Conor Duffy (PhD student).

Congratulating the awardees at the event in Áras an Uachtaráin President Michael D. Higgins said, “I am delighted to receive the wonderful scientists who have been granted SFI Future Research Leaders Awards. This award celebrates their scientific achievements and significant dedication. Their work is evidence of the ongoing world-class research being carried out in Ireland, positioning us as a global leader for scientific excellence.”

Congratulating the awardees, Prof Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, said “The President of Ireland Future Research Leaders Award is designed to attract to Ireland outstanding new and emerging research talent. In supporting these talented and innovative individuals, we are delighted to recognise early career researchers who have already displayed exceptional leadership potential at the frontiers of knowledge. The development of leadership skills in these researchers early in their careers is vital to ensure research and innovation in Ireland continues to progress. Our investment highlights the importance that Science Foundation Ireland places on supporting all stages of academic careers, and on the attraction and retention of star researchers.”

The research of Dr Claire McCoy is based in the Molecular and Cellular Therapeutics Department at the Royal College of Surgeons Ireland. Her research is focused on significantly advancing current therapeutic strategies for the treatment of multiple sclerosis (MS), where Ireland has the highest global incidence. Speaking of her award, she said “Obtaining this SFI Future Research Leaders award is the highlight of my career to-date. Not only does it enable me to lead a growing research team, it will also significantly contribute to the cutting-edge research being conducted at RCSI. Most importantly, it helps to place Ireland at the forefront of multiple sclerosis research worldwide.”

Pictured (l-r): Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland; President Michael D. Higgins; Dr Claire McCoy (MCT dept, RCSI), Dr Francis O’Keeffe (Claire’s Husband)

Reported by SFI communications and Dr Claire McCoy

The Irish DNA Atlas

The Irish DNA Atlas, a study of Irish genetic history and diversity led by researchers at the Royal College of Surgeons in Ireland (RCSI) and the Genealogical Society of Ireland (GSI), has recently published in findings into the genetics of Ireland in the Nature Publishing journal Scientific Reports (The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within Ireland). The Irish DNA Atlas is a cohort of individuals with four generations of ancestry from specific regions in Ireland, recruitment is organised and managed by Seamus O’Reilly at the GSI. Mr O’Reilly helps potential recruits finish, or double-check, family history and pedigree charts for the recruitment process, and mails out sample kits and paperwork for their return to RCSI.
The researchers, led by Professor Gianpiero Cavalleri at RCSI, have found; i) different groups of Irish individuals, clustered by genetic similarity alone; ii) the genetic differences between these groups are incredibly small, iii) members of each of these groups share ancestries from similar regions in Ireland (see image below); iv) a migration event(s) is observed in the north of the island of Ireland that dates somewhere in the 17th and 18th centuries and is from Britain; v) a number of genetic barriers within in Ireland, notably; in the north, and between Leinster and Munster; and finally vi) a significant level of Norwegian-like genetic ancestry throughout Ireland is observed for the first time and this is associated with a genetic migration into Ireland around the turn of the first millennium.
Using the Irish DNA Atlas in conjunction with a dataset of British individuals with regional ancestry (the People of the British Isles Study) the project was able to clusters 2,103 individuals from Ireland and Britain based on genetic similarity as 30 distinct genetic groups (see image 1 for clusters within Ireland). People within the same group are more genetically similar to each other than they are to individuals in other groups. When each Irish individual is colour coded by the group and is placed on a map based on where their great-grandparents were born, we generate a map shown below. Shown to the left are the geographic spread of the identified clusters and on the right a map of Irish kingdoms that represent proto-Provinces circa 800AD.


Analysing the Atlas, the broadest groups within Ireland are either; nearly 100% made up of Irish/Northern Irish individuals (i.e. from the island of Ireland), or are a mix between Irish and mainland British individuals. In the case of the latter, this suggests that those (Irish and mainland British) individuals have shared Irish and British genetic ancestry. The Irish individuals within these mixed groups are mainly from the north of Ireland (predominantly those who are blue crosses in the image above), and the British members are predominantly from the north of England and the south-west of Scotland.
These groups/clusters of near 100% Irish membership are interpreted as mainly ‘Gaelic’ Irish, and the genetic differences between these groups are incredibly small. The groups/clusters are grouped geographically and most are remarkably faithful to the boundaries of the Provinces in Ireland (shown on the left map). We compare these clusters and kingdoms from around 800AD in the above image for illustrative purposes. The reflection between the genetic and historical groups suggests that these Provinces and the kingdoms they represent have subtly impacted the genetic landscape of Ireland. Of particular note is within Co. Clare, which has historically been both parts of Munster and Connacht. Individuals with ancestry from Co. Clare reflect this by showing a mix of genetic groups found within both Munster and Connacht.
In addition to identifying different genetic groups within Ireland, the research sought to investigate whether previous migrations into Ireland had a detectable genetic impact on the genetics within Ireland. Having already identified groups of Irish individuals mainly in the north of Ireland who appeared to a mixture of Irish and British genetics, the researchers tested whether this could be due to a specific event creating these mixed groups. They estimated that these mixed groups are from a number of admixture events in the past, dating around the 17th and 18th centuries.
As well as migrations from Britain, the researchers asked whether evidence of migrations from wider afield, i.e. from continental Europe, could be found. A surprisingly larger amount of Scandinavian – specifically Norwegian – looking ancestry in all our Irish clusters was detected (see below image). This image shows along the horizontal axis each of the 30 genetic groups identified in Ireland and Britain. Along the vertical axis is the average proportion of the genome that’s the closest similarity is found in each of the 10 reference European populations. Ireland and Wales share a lot of French-like ancestry, but Ireland shows a lot of Norwegian-like ancestry compared to England or Wales. In fact, in this Norwegian respect, Ireland shows a similarity to Orkney.

This similar pattern of elevated Norwegian-like in Ireland and Orkney is interesting as Orkney is a region with strong evidence of Norwegian Viking genetic migration and mixture. Therefore the researchers investigated whether this Norwegian ancestry in Ireland was due to a mixture event dating from the time of the Viking activities in Ireland. They dated the ancestry to sometime around 1000 AD, which agrees with a ‘Viking Hypothesis’. This result was perhaps the most surprising using the Irish DNA Atlas, as previous work with Y-chromosomes found no evidence of Norse genetics within Ireland. However now, with whole-genome data, the extent of Norwegian mixture within Ireland is able to be shown.
This research has been funded through a Career Development Award from Science Foundation Ireland. RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2018) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI is a signatory of the Athena SWAN Charter.

Reported by Edmund Gilbert

Characterising Signalling Pathways In Cystic Fibrosis

MCT Research Talks

Cystic Fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. CF is caused by mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene which encodes a chloride channel responsible for helping conduct chloride and other ions across epithelial membranes. Loss of functional CFTR channel disrupts ionic homeostasis resulting in mucus production that clogs the lungs and results in a vicious cycle of chronic infection/inflammation. There are almost 2,000 different variants in the CFTR gene and 70 % of CF patients contain a mutation at position 508, which results in the loss of Phe508 and disruption of the folding pathway of CFTR. ΔF508 CFTR is a trafficking mutant that is retained in the endoplasmic reticulum (ER) and unable to reach the plasma membrane and function correctly as a chloride channel. The Coppinger research lab is focused on understanding the basic mechanisms of CF disease with a focus on the ΔF508 mutation and translating these findings into diagnostics/therapies. We are particularly interested in two areas of research 1. Using basic science technologies to identify novel signalling pathways in CF to discover new CFTR corrector therapies in ΔF508 CF models. We have recently discovered the PI3K/Akt/mTOR signalling pathway to be dysregulated in CF models and a possible therapeutic avenue worth further exploration in CF. Additionally, we are interested in 2. Investigating how diminished ΔF508 CFTR activity leads to heightened inflammatory cell recruitment and CF airway pathogenesis. Exosomes are nanovesicles (40–100 nm) actively secreted by cells and are crucial mediators of intercellular communications. We hypothesised that exosomes may be released from ΔF508 CF patient bronchial cells/fluids and play a role in regulating immune cell function. Preliminary data has confirmed this hypothesis and also indicated exosomal signatures may possibly serve as markers of disease progression in CF. These studies are in collaboration between several groups at the National Children’s Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital University College Dublin, Cystic Fibrosis Unit, St Vincent’s Hospital.

Judith Coppinger and her team: Mark Ward and Zivile Useckaite