MCT Hosts Intergenerational Day Lab Tour

On Thursday 4 October, the Equality, Diversity and Inclusion (EDI) unit welcomed almost 30 family members of staff to RCSI St Stephen’s Green campus for the first-ever RCSI Intergenerational Day. Throughout the day, the guests had the opportunity to learn about a variety of activities at RCSI. MCT hosted a lab tour where guests were introduced to several MCT Principal Investigators who discussed their work and demonstrated how their research is carried out. Four stations focusing on the themes of Breast Cancer, Novel Cancer Therapies, Multiple Sclerosis and Circadian Rhythm and its Impact on Health were featured, led by Dr Sudipto Das, Dr Maria Morgan, Prof Tracy Robson, Dr Claire McCoy and Dr Annie Curtis. Guests were guided around the labs by the MCT Operations Team John O’Brien, Olwen Foley, Anne Grady, Mary Ledwith and Seamus McDonald. Scientists Stephanie Annett; Gillian Moore; Conor Duffy; Chiara DeSanti; Mariana  Cervantes Silva, Richard Carroll and George Timmons also volunteered on the day.
Prof Gianpiero Cavalleri contributed to the day’s activities with a talk on the Irish DNA Atlas. The MCT research projects presented were a hit with our audience evident by the number of attendees, their level of engagement and thoughtful questions. Guests included relatives of MCT staff including Mr Joseph Tighe father of Orna and Mrs McDonald & Curtis – mothers of Seamus and Annie respectively. Julia Morrow of the EDI unit commented that ‘between the MCT lab visit and Gianpiero’s talk, more than one guest commented they wish they could go back and have a more science-oriented career!’ It’s never too late we say!
Written by Maria Morgan

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.

A new mechanism by which the body clock controls the inflammatory response from macrophages

The Curtis lab from MCT in partnership with the O’Neill lab at Trinity College have revealed insights into how the body clock controls the inflammatory response, which may open up new therapeutic options to treat excess inflammation in conditions such as asthma, arthritis and cardiovascular disease. By understanding how the body clock controls the inflammatory response, we may be able to target these conditions at certain times of the day to have the most benefit. These findings may also shed light on why individuals who experience body clock disruption such as shift workers are more susceptible to these inflammatory conditions.
The body clock, the timing mechanism in each cell in the body, allows the body to anticipate and respond to the 24-hour external environment. Inflammation is normally a protective process that enables the body to clear infection or damage, however, if left unchecked can lead to disease. The new study published in the Proceedings of the National Academy of Sciences (PNAS), a leading international multidisciplinary scientific journal.
Dr Annie Curtis, Research Lecturer in the Department of Molecular and Cellular Therapeutics at RCSI and senior author, explained that: “Macrophages are key immune cells in our bodies which produce this inflammatory response when we are injured or ill. What has become clear in recent years is that these cells react differently depending on the time of day that they face an infection or damage, or when we disrupt the body clock within these cells”.

Some members of the Curtis lab involved in this project: Dr. Richie Carroll (far left), Dr. Annie Curti,  Dr. Mariana Cervantes, George Timmons (far right)

Dr. Jamie Early, the first author on the study, said: “We have made a number of discoveries into the impact of the body clock in macrophages on inflammatory diseases such as asthma and multiple sclerosis. However, the underlying molecular mechanisms by which the body clock precisely controls the inflammatory response were still unclear. Our study shows that the central clock protein, BMAL1 regulates levels of the antioxidant response protein NRF2 to control the inflammatory response from macrophages.
“The findings although at a preliminary stage, offers new insights into the behaviour of inflammatory conditions such as arthritis and cardiovascular disease which are known to be altered by the body clock”, added Dr Early.
Funded by Science Foundation Ireland, the research was undertaken in collaboration between RCSI, Trinity College Dublin and the Broad Institute in Boston, USA.

Here is the  link to the paper titled ” Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2

Annie Curtis

Mechanobiology – the ‘dark matter’ of cancer and immunity

MCT research seminar

The way we act very much depends on our surroundings; not the least on the weather conditions. In a similar way, cells in our body very much depend on what is going on around them. It has been known for a long time that the specific niches in which cells reside impact on the cellular phenotype. While most researchers have looked at chemical signals – either released into the environment or reflecting the composition of the extracellular matrix – it is becoming increasingly clear that also physical properties, such as stiffness and topography, are sensed by a wide variety of cells and influences their decisions.

It is our pleasure to welcome Prof Viola Vogel this Monday at RCSI for the MCT research seminar.

July 16th, 4.00 pm, Albert Lecture Theatre “How does the mechanobiology of extracellular matrix steer cancer progression?

Prof Vogel and her laboratory at ETH Zurich have pioneered the field of mechanobiology. Her earlier work focused on how proteins act as mechanochemical switches to transduce mechanical signals from the ECM into the cell. More recent work addresses the importance of tissue strain in the development of tumours. Prof Vogel will also share her latest results on how physical constraints affect decision making of macrophages.

Anyone who is interested in getting a different viewing angle on cancer and immunity is heartily invited! To steer your personal decision making towards attending the talk, refreshments will be served from 3.30 pm on in the Atrium.

Ingmar Schoen

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

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!!!

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