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

Our Educator’s Vision – The White Coat Ceremony

Did you ever wonder what was the significance of the white coat ceremony and what impact it can have on students and faculty who attend?

Dr. Orna Tighe, Dr. Judith Strawbridge, Dr. Alice McGarvey and Prof Hannah McGee explain the evolution of this ceremony at RCSI on the blog of Journal of Interprofessional Care. They touch on the history of the white coat ceremony, it’s associated symbolism, how this ceremony became a tradition in RCSI and has now developed into a unique interprofessional White Coat ceremony, offering an opportunity for multidisciplinary healthcare professionals to develop interprofessional socialization at an early point in their education. The philosophy and the value of this ceremony in RCSI are discussed.

Have a look at some messages from the story and read the original here.

“We recognized that the ceremony needed to be more than just bringing students together and consequently it was developed to ensure that student voice was central, while emphasizing institutional support for interprofessional collaboration”…

“In summary, our experience suggests that the initial power of the white coat metaphor has evolved within RCSI to deliver what is a novel inspirational Interprofessional Ceremony in the very first week of the students’ programs”

 

 

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/

 

Congratulations to ‘Drs’ Shane O’Grady and Brian Mooney

Dear all,

Please join me in offering congratulations to ‘DrsShane O’Grady and Brian Mooney who successfully defended their PhD thesis yesterday:

Shane’s: Investigation of the functional roles of calcium channels, inflammatory cytokines and tumour micro-environmental factors in a human in vitro model of breast cancer calcification
Supervisor: Maria Morgan
Brian’s: The role of the anorectic neuropeptide CART in breast cancer. Supervisor: Darran O’Connor

 

 

Well done to all.

Tracy

Tracy Robson

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!!!

MCT Research at the 54th Irish Association for Cancer Research Meeting 2018

Many MCTers presented their research at the 54th Irish Association for Cancer Research Meeting on February 22-23, 2018. The annual IACR meetings bring together the Irish cancer research community and distinguished international speakers. 260 attendees registered for the meeting with 150 abstracts accepted for oral and poster presentations. Notably, the IACR meeting committee creatively shapes the way this conference run. This year, the most dynamic session – Oral Poster Presentations (Prof. John Fitzpatrick Medal, 5 min talk+1 min Q&A) was set for the lay audience with the judging panel consisting of patients, patient advocates and researchers. Very interesting experience, have to say. Two MCT research studies were selected for this session: Olga Piskareva presented the collaborative project between her team and Prof Fergal O’Brien (TERG) “3D Tissue-Engineered Cell Model Of Neuroblastoma For Evaluating Cytotoxic and miRNA-Targeted Therapeutics” and O’Connor’s collaborative project on “RNA Sequencing Identifies BRD3 As A Novel Therapeutic Target In Invasive Lobular Carcinoma Breast Cancer” was presented by Kathryn Haley. Darran O’Connor himself was an invited plenary speaker. He talked about “The Power Of 1: What Can We Learn From Molecular Case Studies?” at the plenary session Emerging Techniques In Biomarker Discovery, Drug Development And Patient Stratification. MCT had a spot at the Proffered Paper Session with John Nolan presented the first data of the NCRC funded project “Modulation of Drug Resistance in High-Risk Neuroblastoma Through Exosomal miRNA”. Many other MCTers had Posters. For Shane O’Grady and Lisa Dwane, it was the last conference in the PhD status and for Olga Piskareva – in her role of Honorary Treasurer f0r the IACR!

Well done to all!

The 55th Irish Association for Cancer Research Meeting will be taking place in Belfast.

Reported by Olga Piskareva

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