Circadian Immunometabolism. What it is and why your immune system will not thank you for eating curry chips at 2am after the disco

MCT Research Seminar

The Curtis Clock laboratory has a real interest in metabolism, which is a really broad term and means different things to different people. We are interested in how different fuels (sugars , fats, proteins) are metabolised (broken down) within immune cells, and if this has an impact on how that immune cell functions. The key metabolic organelle within a cell is the mitochondria, that is where the breakdown parts of these fuels end up and are converted to energy (ATP). We are a Clock lab, so our raison d’etre (so to speak) is to unravel how different fuels are metabolised within immune cells at different times of day and how the mitochondria work at different times of day, and how that impacts the response of the immune cell at that time of day. This is what we now term “Circadian Immunometabolism”. This leads me on nicely to our title, before the age of electricity, our forefathers never ate in the middle of the night, we believe that our immune system becomes dysfunctional when it has to deal with food during a time when we now believe our immune system is undergoing repair and restoration. So to begin to get at these big questions, Mariana and George have two exciting projects ongoing. Mariana, who is a postdoc in the laboratory, will show how our mitochondria are changing over the course of the day in dendritic cells (these are cells of the innate immune system and are the ones that feed information to our adaptive immune system) (see Fig. 1). The title of her talk is

“Those mitochondria have got rhythms! Mitochondrial activity and antigen processing in dendritic cells is dependent on the molecular clock protein BMAL1”.

George, a PhD student in the lab, is dissecting down into the cells to figure out how the electron transport chain (the side of action for ATP synthesis) is controlled by the clock. The title of his talk is

“Metabolic pathways in a macrophage lacking a molecular clock”

Mitochondria have a very important role in cellular metabolism, their morphology is completely different during the day (elongated) (yellow) or during the night (fragmented) (blue) nucleus (gray)

Annie Curtis

More details of what we do can be found here: www.Curtisclocklab.com

Harnessing FKBPL to target cancer and vascular disease

Pathological blood vessel formation (angiogenesis), or the inability of endothelial cells to perform their physiological function (endothelial dysfunction), are defining features of disease. The endothelium actively controls vessel integrity, vascular growth and remodelling, tissue growth and metabolism, immune responses, cell adhesion, angiogenesis, haemostasis and vascular permeability.  It is, therefore, a vital and largely unexploited target for novel therapies.

Prof Tracy Robson’s team have identified and characterised a novel anti-angiogenic protein, FK506 binding protein like – FKBPL, significantly advancing our understanding of the anti-angiogenic process, in particular, how tumours recruit blood vessels to support their growth. This led to a collaborative study with Almac Discovery to develop therapeutic peptides based on FKBPL’s active domain to explore their potential in cancer by targeting the ability of tumours to recruit blood vessels to grow, invade and metastasise beyond the site of the primary tumour.  The team are also testing the ability of these peptides to sensitise tumours to current therapies and to target cancer stem cells that lead to the onset of resistance and/or recurrent disease.   Importantly, these studies led to a ‘first in man’ phase I clinical in cancer patients where the clinical candidate drug, ALM201, was very well tolerated over a wide range of doses.  Prof Robson’s team (Dr Stephanie Annett and Dr Gillian Moore) will discuss this data together with new data suggesting a strong role for FKBPL in vascular endothelial dysfunction and possible implications therefore in other diseases associated with vascular disease.

Graham Cotton, Tim Harrison, Tracy Robson, Gillian Moore, Seamus Browne and Stephanie Annett (left to right)

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

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