Regenerative inflammation in the CNS: Innate and adaptive immune mechanisms in myelin repair

MCT Research Seminars – October, 8th 2018

Dr Dombrowski’s research focuses on immune mechanisms in tissue damage and repair. Tissue damage can occur in infectious (e.g. bacteria, virus, fungi) or sterile settings (e.g. trauma, autoimmune attack). The Dombrowski group is primarily interested in the underlying immunological mechanisms that direct tissue repair and regeneration with the goal to identify novel therapeutic targets for immune-mediated diseases such as Multiple Sclerosis (MS).
Despite driving pathology in many diseases, the immune system is required for tissue regeneration. Innate immune receptors sense disruption of tissue homeostasis initiating a regenerative immune response that leads to the repair of the damaged tissue. Our central goal is to elucidate the mechanisms of regenerative inflammation, in particular, the role of the innate immune system in myelin regeneration in MS.
In MS the myelin sheath that covers nerve fibres is damaged due to an autoimmune attack against proteins in the myelin sheath. As a result, the nerve fibres die leading to a loss of function, which can result in paralysis and other neurodegenerative symptoms. There is no cure for MS to date and there are no therapies that can restore damaged myelin in order to prevent nerve loss.
Current projects of the group investigate the function of inflammasomes during myelin damage and regeneration in the central nervous system (CNS) and the effects of IL-1 cytokines on oligodendrocyte progenitor cells, stem cell-like cells in the CNS that produce myelin. Other projects in the group investigate the role of inflammasomes in regenerative inflammation after infectious tissue damage and the role of e-cigarette vapour as an inflammasome activator. Dr Dombrowski has published her work in high-impact journals (e.g. Nature Neuroscience 2017) and her research has been recognized in prestigious awards including an Early Career Fellowship from The Leverhulme Trust and the invitation to the 64th Lindau Nobel Laureate Meeting for Physiology and Medicine as one of ten UK representatives.

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)

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

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

A great week for Body Clock Research in MCT RCSI

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:

Siliconrepablic.com

EurekAlert

RTE

Written by Annie Curtis