Timely Announcement for Nobel Prize

 

Last Monday while in Amsterdam with my Mam and two sisters, a friend of mine sent a text to let me know that the 2017 Nobel Laureates in Physiology and Medicine were Hall, Rosbash and Young.  They were awarded the Nobel for their work in identifying the key genes that create circadian or body clock rhythms in the fruit fly. My feet literally were stuck to the ground, it was thrilling to know that these gentlemen would get the recognition that they so deserve, but also what this will mean for the field of science that I am so passionate about. The body clock is the molecular timekeeping system that exists in practically every organism on the earth and in every cell in our body. Simply put, it allows the cell to tell what time of day it is. Why is that important? We live on a spinning planet and because of the earth’s rotation to the sun, all life on earth has been subjected to daily periods of light and heat, dark and cold. The body clock allows us to anticipate and respond to these 24-hour predictable environmental changes and synchronises our physiology to it. For example, the body clock increases cortisol levels in the body ahead of awakening, this helps us to become active once we wake. The body clock also increases expression of digestive enzymes in the intestinal tract during daylight hours (this is why curry chips at 3am is never a great idea!).

Back in the 80’s Hall, Rosbash and Young independently isolated a gene called Period, they showed how the gene encodes a protein PER that builds up in cells at night and degrades during the day. This daily rise and fall of PER essentially allow the cell to track time of day. How thrilling it must have been for them to observe this daily change in the mRNA levels of Period gene (Figure 1- black line), all that is changing along the x-axis is the time of day.

So what does this mean three decades later? We have made great strides in understanding how the molecular clock works. We now know that the clock keeps time by a series of transcriptional-translational feedback loops. We also know that the clock controls 40% of all coding genes within the body. The body clock controls all aspects of our physiology from metabolism to immunity.

Many diseases, such as osteoarthritis and cardiovascular disease, are highly time of day dependent. Moreover, it appears that disruption of our body clocks, caused by our non-stop 24/7 lifestyle and exposure to artificial light at all times of day, is partly responsible for the increase in chronic inflammatory diseases. Unfortunately, most cell culture systems are not synchronized with the time of day, and this, in my opinion, is one of the main reasons that many researchers unknowingly neglect this field. Finally, we are making great strides in attempting to time specific treatments to the right time of day, an area called chronotherapy. Therefore, it is my hope that this increased awareness of the body clock will bring more researchers into this fascinating field. If we don’t fully understand how our body clock controls physiology and disease we will certainly be left in the dark.

Annie Curtis is a Research Lecturer and runs the Immune Clock laboratory at MCT and is fascinated by all things body clock related.

 

Congratulations!

Dear all,

Please join me in sending congratulations to the following staff: Sudipto Das and Jennifer Dowling on their appointment as Honorary Lecturer[s] within MCT, recently approved by Academic Council.

Sudipto Das on the award of best poster presentation in the Post-doctoral researcher category for poster titled “Using next-genera-on sequencing strategies to guide precision oncology in cases with atypical clinical presentation” at the Irish Society for Human Genetics Annual Conference held at Croke Park, Dublin on 15th Sep, 2017.

Jamie Early, student with Annie Curtis, for the best short talk at the Irish Society for Immunology Annual meeting. The title of talk: The circadian clock protein BMAL1 regulates inflammation in macrophages via the NRF2 antioxidant defense pathway”.

And finally to ‘Dr’ Rana Bakhidar PhD, who successfully defended her thesis last week. The title of her thesis is ‘Nanoparticles Used in Drug Delivery and Targeting: Understanding the relationships between Nanoparticle Quality And Interaction With Platelets’. Supervisor: Dr. Sarah O’Neill and Co-supervisor, Dr Zeibun Ramtoola, School of Pharmacy,

Well done to all!
Best wishes,

Tracy

Tracy Robson
Professor & Head of Molecular & Cellular Therapeutics (MCT)

Irish Centre for Vascular Biology Achievements

Bayer announced awards of $2 Million in Hemophilia Research and Patient-care Grants to 16 People at The International Society on Thrombosis and Haemostasis 2017, held in Berlin in July.

Congratulations to Dr. Roger Preston, Irish Centre for Vascular Biology[ICVB], (MCT) who was awarded a prestigious Special Project Award (€200,000) from the Bayer Haemophilia Award Programme to develop novel pro-hemostatic agents for the enhanced treatment of patients with haemophilia.

There was a strong representation from MCT at the ISTH Congress including Professor Dermot Kenny, Professor James O’Donnell, Dr. Roger Preston and their respective teams, and Dr. Dermot Cox, President, SSC* 2018. [*SSC:The Scientific and Standardization Committee].

Orla Willis Fox, Phd student with Dr. Roger Preston (ICVB/MCT), was awarded an ISTH Young Investigator Award for submitting one of the highest ranked abstracts. Her abstract title was ‘Inhibition of Activated Protein C Aspartyl Beta-hydroxylation Restricts Anticoagulant Function but Enhances Cytoprotective Signaling Activity’.

Professor James O’Donnell, ICVB/MCT presented an invited state-of-the-art lecture on his landmark studies on VWF and Cerebral Malaria,Dr. Michelle Lavin, ICVB/MCT on LOVIC [The Low Von Willebrand factor Ireland Cohort (LoVIC)] study, Dr. Sonia Agulia, ICVB/MCT on The Role of Sialylation in low VWF levels andSoracha Ward, ICVB/MCT gave a presentation on VWF Clearance.

Professor James O’Donnell at the International Society on Thrombosis and Haemostasis Congress, Berlin

Additionally, there was significant interest among the attendees in the ISTH SSC 2018 Annual Meeting which will be held in Dublin 2018;  Dr. Dermot Cox, President, SSC 2018 anticipates a record attendance of 3,000 delegates for the Dublin meeting. Olwen Foley , (MCT) managed the Irish stand.

ICVB/MCT

Dr Annie Curtis wins L’Oréal-UNESCO Fellowship For Women in Science

Our congratulations to Dr Annie Curtis with L’Oréal-UNESCO Fellowship For Women in Science Award! Well done!

She was awarded a prestigious L’Oréal-UNESCO For Women in Science 2017 Fellowship at a ceremony held at the Royal Society in London on May 5th.

She was one of five winners of these fellowships and the only Irish winner this year. The fellowship will support her research into understanding the precise mechanisms by which the body clock restrains inflammation from a key immune cell called the macrophage.

Professor Tracy Robson said: “This is a fantastic achievement and I am proud to congratulate Dr Annie Curtis on this highly competitive award for which there were nearly 300 applicants. It is a great testament to her research within the recently established Immuno-Clock Lab. Annie will be an excellent ambassador for Women in Science and this award reflects the world-class research ongoing at RCSI. Indeed the only Irish winners of these For Women in Science fellowships now reside within this institution.”

Recipients of L’Oréal-UNESCO For Women in Science 2017 Fellowship. Courtesy of RCSI Communications Department

The recipients of L’Oréal-UNESCO For Women in Science 2017 Fellowship:

  • Dr Annie Curtis, Royal College of Surgeons in Ireland, the human body clock and inflammation
  • Dr Radha Boya, University of Manchester, Nanoscience
  • Dr Manju Kurian, UCL Great Ormond Street, Neurology
  • Dr Bethan Psaila, University of Oxford, Haematology
  • Dr Priya Subramanian, University of Leeds, Mathematics

RCSI Communications Department

 

Japan Society for Promotion of Science – Short-term post-doctoral fellowship

Following a workshop conducted at Hoshi University, Tokyo, Japan organized through the ISCA-Japan initiative funded by SFI in October, 2015 a successful collaborative initiative was established between Dr. Sudipto Das (MCT, RCSI) and Prof. Hiroko Ikeda (Department of Neurophysiology, Hoshi University) to investigate the role of epigenetic modifications like DNA methylation in driving a neuronal dysfunction phenotype associated with Diabetes mellitus (DM). Moving this collaboration forward with support from his collaborators at Hoshi University Dr. Sudipto Das has recently received a prestigious short-term post-doctoral fellowship to further his work at Hoshi University from the Japan Society for Promotion of Science (JSPS), which would essentially cover travel, subsistence and a research consumable allowance of 562,000 Japanese Yen. As a part of this fellowship, Dr. Das will travel to Japan for a period of 1.5 months in January 2018. The successful completion of the proposed project as a part of this proposal will for the first time allow the scientific community to understand as to how epigenetic modifications like DNA methylation impact on neurological dysfunction in endocrine

The successful completion of the proposed project as a part of this proposal will for the first time allow the scientific community to understand as to how epigenetic modifications like DNA methylation impact on neurological dysfunction in endocrine related disorders such as DM, thus opening up avenues to utilize this modification to potentially predict such conditions in DM patients.

Sudipto Das

MCT Awards at Research Day 2017

Dear all,

MCT was well represented in the award ceremony at the recent Research Day; our congratulations go to the following:

Dr Mark McCormack, for receiving prizes in the RCSI Author Citations Prizes in two categories – the 2011 Most Highly Cited RCSI Senior Authored Paper and the 2011-2015 Most Highly Cited RCSI Senior Authored Paper with International Collaboration – for his paper entitled “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans” published in the New England Journal of Medicine.

Dr Cathy Wyse, as part of Dr Annie Curtis’s group, was presented a prize for the front cover illustration of the RCSI Research Day abstract book, for a striking image of glial cells at the junction between the brain and pituitary gland.

Tony McHale, PhD student at the School of Pharmacy, & MCT, and the Irish Centre for Vascular Biology, RCSI received the prize for the best postgraduate oral presentation, for his talk on the topic of “First in Class Potential Novel Drug for the Treatment of Sepsis Caused by Urinary Tract Infections”.

Medical student Jack Donohue [RSS student], was awarded the Dr Harry O’Flanagan Prize for Excellence in Undergraduate Research for the best undergraduate oral presentation for a project carried out as part of the RCSI Research Summer School entitled “Sanger Confirmation of Suspected Epilepsy-Related Pathogenic Variants Identified Through Next-Generation Sequencing”.

Very well done to all!

Tracy Robson

Kay McKeon

8 February 2017

An informal, private reception was held in the College for Kay McKeon on Wednesday, 8th February, to mark her retirement and contribution to RCSI after 39 years.

Kay joined Clinical Pharmacology in 1978 and with Prof. Kevin O’Malley was responsible for commissioning the then ‘new’ laboratories. She continued to play a fundamental role in developing Clinical Pharmacology’s laboratories and building the department’s reputation through the 1980s and 1990s into RCSI’s premier research department.

She played a central role in assisting Kevin O’Malley’s successor, Prof. Des Fitzgerald, in securing RCSI’s first large HEA-PRTLI and SFI grants, working long hours with the intricate details and logistics for such applications.

During this period, Kay was seconded to oversee the development of the RCSI Centre for Human Proteomics, before returning to base and seeing in another period of change on the departure of Prof. Fitzgerald and formation of Molecular & Cellular Therapeutics (MCT) from the Departments of Biochemistry and Clinical Pharmacology under Profs. David Croke and John Waddington as HODs; she played a key role in the management of MCT as a member of it’s Executive.

At a more personal level, Kay was someone who carried out her responsibilities in a genuinely supportive and politically astute manner; many appreciated her sensitivity, in assisting all ‘new staff’ settle in and in maintained balance and stability in overseeing laboratories with up to 100 staff.

Yet in addition to this, Kay also found the time to contribute more broadly to RCSI, particularly its philanthropic activities, for example, the Old Folks Christmas Lunch for those living in the vicinity of the College and related activities; an all-too-rare rare combination of professionalism and altruism.

An important part of what Clinical Pharmacology and MCT has achieved serves as her legacy to the College, in making MCT what it is today and the entity that Prof. Tracy Robson has recently inherited.

Hebrews 6 (10 … 19): ‘For God would not be so unjust as to forget all that you did for love of his name, when you rendered service to his people, as you still do … It is like an anchor for our lives, an anchor safe and sure’.

Kay has been an ‘anchor safe and sure’ across four decades. We thank you, Kay, for everything you’ve done for Clinical Pharmacology, MCT, RCSI and the community at large and wish you well for the future.

A pharmacogenomic exploration of adverse drug reactions in epilepsy (PGXOME)

For most people with epilepsy, long term treatment with anti-epileptic drugs (AEDs) are necessary to prevent the seizure, and 40% do not respond to the first line of AED, leading to an often lifelong odyssey of trial and error towards effective treatment that is often not found. Epilepsy is primarily treated using AEDs, but these are associated with a considerable risk for adverse drug reactions (ADRs), some of which have been shown to have a genetic predisposition. For example, the genetic variant HLA-A*3101 is a common risk factor for rash and severe blistering skin reactions with the drug carbamazepine (Tegretol) in Europeans. However there are few other predictors of some more common ADRs.

Dr. Mark McCormack

The EpiPGX Consortium was established to identify genetic biomarkers of epilepsy treatment response from patient centres across Europe. The EpiPGX Consortium has generated genetic profiles on over 8000 patients with matching detailed drug response and medical histories. In order to investigate the links between genetic profiles and ADRs in epilepsy, Dr. Mark McCormack will travel to UMC Utrecht, the Netherlands for one year on a  Marie-Skłodowska-Curie Fellowship from the European Commission.

The aim of this fellowship is to identify clinically useful genetic variants to predict adverse reactions to AEDs. This will help optimize personalized treatment, limit the trial and error approach of AED choice, and thus improve medication safety and quality of life in epilepsy.

MCT student, Lisa Dwane, talks about her research and recent achievements

cropped-RCSI-logo-1.jpgFollowing completion of my Pharmacology degree in UCD, I began a PhD in breast cancer research under the supervision of Dr. Darran O’Connor, a career I have always been very determined to follow. My research is focused on endocrine-driven breast cancer and understanding the molecular mechanisms that drive this subtype of cancer. Currently, half of breast cancer patients that receive anti-endocrine therapies will relapse, so there is an urgent need for the identification of novel therapeutic targets. Our research is focused on the deubiquitinating enzyme USP11, which we believe plays a key role in driving endocrine-driven breast cancer. When we silence USP11 in vitro, we see a reduction in estrogen receptor activity and cell viability. During the final year of my PhD, I hope to elucidate the mechanism by which USP11 plays this role, and determine the prognostic relevance of USP11 in breast cancer. This could potentially lead to a better understanding of endocrine-driven breast cancer and with further validation, USP11 may represent a novel therapeutic target.

Lisa Dwane presents her research at the Irish Cancer Society’s Researcher of the Year Award. december, 1st, 2016. TCD
Lisa Dwane presents her research at the Irish Cancer Society’s Researcher of the Year Award. December, 1st, 2016. TCD

As a pharmacologist, I was thrilled to win best oral presentation at the Irish Association of Pharmacologists Annual Meeting! The standard of talks throughout the day were excellent, with a wide range of topics explored. I was also a finalist for the Irish Cancer Society’s Researcher of the Year Award, which took place 1st December at Trinity College Dublin. The purpose of the evening was to communicate our research to a lay audience, which proved more difficult than expected! Although I didn’t take home the award it was a very enjoyable evening, and the experience was invaluable. As scientists it is important for us to share and communicate our research with the general public and this was a skill I gained from the night!

Winners and finalists for the Irish Cancer Society’s Researcher of the Year Award
Winners and finalists for the Irish Cancer Society’s Researcher of the Year Award