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 Lab Safari Activities

On November 14th, we welcomed almost 50 secondary school students at our Department for Lab Safari. The event was designed to encourage young people to consider a career in Science, Technology, Engineering, Maths and Medicine through hands-on experience and demonstrations prepared by our researchers. We developed 6 different workstations focused on Cancer biology and biomarkers, Drug Discovery, Multiple Sclerosis, Human Genetics and Immunology/Body clock

Tracy Robson

The event was opened by Prof. Tracy Robson, Head of MCT, sharing her career path in research and lessons that she learnt. Dr Avril Hutch, Head of RSCI Equality and Diversity Unit, also spoke about stereotypes in STEMM careers and having an awareness of unconscious bias.

Caragh Stapleton

Human Genetics
Our workstation was led by Caragh Stapleton, Katherine Benson and Edmund Gilbert, centered around human genetics. Our activity set out to teach participants about inherited traits and demonstrate how variation in our DNA influences our physical attributes. We investigated a number of traits including PTC taster (using PTC taste strips), colour blindness, widows peak, tongue rolling, attached earlobes, bent little finger, eye colour and red hair. Each participant noted whether or not they had the given trait and we then discussed the hypotheses of the genetic variants influencing the different traits.

Olga Piskareva and John Nolan

Cancer Biomarkers
Our workstation was led by Olga Piskareva and John Nolan. We explained the concept of biomarkers and the importance of discovering novel biomarkers for neuroblastoma, a childhood malignancy. Various chromosomal aberrations can be biomarkers of neuroblastoma aggressiveness. One of the strongest predictors of rapid neuroblastoma progression is MYCN status. We selected several neuroblastoma cell lines with known MYCN status providing a good illustration of biomarker’s quantity. Using immunodetection, we visualised the differences in the MYCN presence.

Mariana Patricia Cervantes Silva

Immunology/Body Clock
Our workstation was led by Annie Curtis, Mariana Patricia Cervantes Silva, George Timmons and Cathy Wyse. The theme of our activity was on the body clock and immune function. We discussed with the students why they get jet lag and what that has to do with their body clock. Students then moved to the first station where they got a chance to add colouring to macrophages, so we had red, yellow, blue and green macrophages and were able to look at their coloured macrophages under a microscope. Then they moved to the next station where they got to see the master clock which resides in the hypothalamus of the brain under a microscope. Finally, we displayed some images of activated macrophages and explained their function.

Stephanie Annett

Cancer Cell Biology
Our workstation lead by Sudipto Das, Gillian Moore and Stephanie Annett, focused on showcasing the various laboratory-based approaches applied regularly to identify and investigate novel gene or protein-based biomarkers of cancer progression. Within our workstation, we highlighted three key areas including how samples following biopsy from a cancer patient are used to construct tissue microarrays which are used for assessing the importance of a certain protein in cancer. This was followed by demonstrating a particular tissue culture-based method used to study anti-cancer properties of drugs and finally displaying an array of microscopic images of blood vessels developing in a given tumour.

Conor Duffy

Multiple Sclerosis
Our workstation was led by Claire McCoy, Remsha Afzal and Conor Duffy. The research focus at our lab safari station was Multiple Sclerosis (MS). We explained how the causes of MS are unknown, but that it is characterised by an influx of immune cells into the brain and spinal cord. Our research aims to investigate one type of immune cell called the macrophage. We aim to understand the damage macrophages cause in MS and if we can reverse this to provide an alternative tool for MS therapeutics. We really enjoyed explaining our research at the Lab Safari, where we showed students how MS impacts on brain function and showed them examples of activated macrophages under the microscope.

Padraig Norton

Drug Discovery
Our workstation was led by Dermot Cox and Padraig Norton. Students were given a brief history of drug discovery. Then they were introduced to the basic concepts of how a drug binds to its target and the different ways in which a drug can bind. Students were then shown a demonstration of molecular docking on a computer whereby a small molecule, or drug candidate, was virtually docked into a target binding site using the software.

Tracy Robson and Anne Grady

The event was led by Dr Maria Morgan, Anne Grady, Prof. Tracy Robson, Dr Olga Piskareva and John O’Brien. Guides on the evening included Olwen Foley, Camille Hurley, Mary Ledwith, Seamus McDonald and Shane O’Grady.

Irish Association For Cancer Research Meeting 2017

Irish Association for Cancer Research – Annual Meeting takes place at Newpark Hotel, Kilkenny on Thursday 23 and Friday 24 February 2017.

MCT cancer researchers secured oral presentations at different sessions. Prof Ray Stallings is a guest speaker at the Plenary Session focused on challenges in childhood cancers. He will be discussing ‘Modulation of neuroblastoma phenotype with epigenetically regulated miRNAs’.

Stephanie Annett will be giving a talk ‘FKBPL as a novel prognostic biomarker and therapeutic agent in high-grade serous ovarian cancer’ at Proffered Paper Session on Thursday morning. Two Irish Cancer Society funded PhD students will be discussing their findings at the Irish Cancer Society Scholar and Fellow Presentation session. Louise Walsh – ‘RNA sequencing identifies bromodomain proteins as a therapeutic strategy for invasive lobular carcinoma’ and Brian Mooney – ‘Expression of the cocaine- and amphetamine-regulated transcript recruits BAF chromatin remodelling complexes to the estrogen receptor’.

Good luck to our presenters!

Olga Piskareva

 

 

miR-155, a master regulator of the immune response

MCT Research Talks – 13th February 2017

Dr. Claire McCoy

Background

I have recently arrived as a Lecturer in Biochemistry/Immunology within the Molecular and Cellular Therapeutics Department at RSCI. I am a dedicated and passionate Biochemist/Immunologist who obtained a BA (Mod) in Biochemistry from Trinity College Dublin in 2001.

Dr Claire McCoy

In 2006, I completed my PhD at the University of Dundee, Scotland after which I conducted my postdoctoral training in innate immunology with Prof Luke O’Neill. In 2010, I received a Marie Curie Mobility Fellowship where I gained scientific independence and re-located to the Hudson Institute of Medical Research in Melbourne, Australia. In 2014, I was awarded an Australian NHMRC project grant enabling me to lead an independent research team, conducting my research specifically on the regulation of microRNAs in innate immune cells, with a particular focus on inflammatory diseases such as Multiple Sclerosis.

Specific Research
My lab aims to understand how microRNAs regulate inflammation in disease. Our particular focus is how the pro-inflammatory microRNA, miR-155, plays a fundamental role in one immune cell subset called the macrophage. Macrophages are the sentinel cells of our immune system and quickly respond to infection to clear invading microbes. However, in chronic inflammatory diseases and autoimmunity, the presence of macrophages largely contributes to the damage, tissue destruction and symptoms associated with these diseases. Our research has shown that miR-155 is a key driver of this response. My lab aims to identify the molecular and functional mechanisms that underpin inflammatory macrophages, with the aim that miR-155 inhibition will lead to real therapeutic potential.
Multiple Sclerosis (MS) is a progressive degenerative disease where the prevalence in Ireland far exceeds the global average. Disease onset occurs between 20-40 years, an age critically affecting working and family life. To this day, there is no known cause and no cure for MS. Although, the early disease can be managed by current drug therapies, there is no treatment at the later progressive stages of disease, and no known treatments to repair the damage caused to the central nervous system. My research aims to uncover the role of macrophages in MS, and the contribution of miR-155 in this effect.

Awards
Claire McCoy is the recipient of a prestigious Marie Curie International fellowship and an Investigator Project Grant from the National Health and Medical Research Council (NHMRC), Australia. Altogether my research has attracted €800K in both national and international funding. I have published >21 highly cited and seminal publications in Nature Reviews Immunology, Nucleic Acids Research, Journal of Leukocyte Biology and Journal of Biological Chemistry. I am book editor for Springer Science, USA, as well as peer reviewer for international journals and funding agencies.

I will be talking about my research at 12pm TR4, Monday 13th Feb. The title of my talk will be ‘miR-155, a master regulator of the immune response’.

ALL WELCOME!

Dr. Claire McCoy

Lecturer in Biochemistry/Immunology,
Royal College of Surgeons in Ireland,
123 St Stephens Green,
Dublin 2,
Ireland.
Tel: 01-4025017
Email: clairemccoy@rcsi.ie

Targeting drug resistance in neuroblastoma

MCT Research Talks 5th December 2016  rcsi-logo

Cancer Genetics Group

Neuroblastoma is a childhood cancer caused by the abnormal growth and development of neural crest cells (1). The disease commonly affects children age 5 years or younger. Approximately 50% of children have cancer cells that have migrated to distant sites in the body and formed tumour masses at the time of diagnosis. The main challenge in treating neuroblastoma is to combat tumour metastasis and development of resistance to multiple chemotherapeutic drugs. Despite major advances in available therapies, children with drug resistant and/or recurrent neuroblastoma have a dismal outlook with 5 year survival rates of less than 20%.

Research of Prof. Stallings lab is focused on elucidating the molecular events that contribute to the development and progression of neuroblastoma (2).  A major area of research involves the identification and functional analysis of microRNAs that contribute to chemotherapy resistance in neuroblastoma, along with the development of microRNA-mediated therapeutics.

The main research projects were presented at the Departmental meeting on December, 5th.

Microscopic examination of drug resistant neuroblastoma cells KellyCis83. Cells look healthy and can be kept for another 2-3 days to form a more dense population.
Microscopic examination of drug resistant neuroblastoma cells KellyCis83. Cells look healthy and can be kept for another 2-3 days to form a more dense population.

The first talk by Olga Piskareva has explored how current concepts of development of drug resistant, tumour microenvironment and cell-to-cell communication can be applied to reconstruct relapsed or drug resistant neuroblastoma microenvironment using 3D tumour models.

TEM analysis of exosome fractions. Vesicle sizes range from 30 to 200nm in Kellycis83 (A) and Kelly (B) neuroblastoma cells. (C) EVs which appear larger than the 100 nm upper limit for exosomes (D) Close up of the dried exosome preps identify the typical bowl shaped morphology associated with TEM images of exosomes. (3)
TEM analysis of exosome (EV) fractions. Vesicle sizes range from 30 to 200nm in Kellycis83 (A) and Kelly (B) neuroblastoma cells. (C) EVs which appear larger than the 100 nm upper limit for exosomes (D) Close up of the dried exosome preps identify the typical bowl shaped morphology associated with TEM images of exosomes (3).

The second talk was presented by Ciara Fallon. Ciara is our StAR PhD student. She has selected the project ‘Exosome mediated drug resistance in high-risk neuroblastoma’ as her first choice.  At the moment she is doing her lab placement in Cancer Genetics group as a part of the RCSI StAR PhD Programme. Built upon results of the former BioAt PhD Student Ross Conlon (3), Ciara’s project is focused on the validation of exosomal miR-548d-5p as a regulator of cell viability and proliferation in cisplatin sensitive and resistant neuroblastoma cell lines.

Finally, the last, but not least was a talk by John Nolan. His talk entitled “MiRNA-124-3p Reduces Cell Viability in Cisplatin Resistant Neuroblastoma Cell Models” was focused on the results submitted to the Royal College of Surgeons for the Degree of Doctor of Philosophy. His studies cover the development of cross resistance to other drugs, investigation of common altered proteins and signaling pathways in cisplatin resistant neuroblastoma cell lines and validation of miRNA that can target these proteins and stop cell proliferation. Part of the results was published last year in Cancer Letters (4).

The work carried out in Prof. Stallings lab is supported through the research grant to Prof. Ray Stallings and PhD fellowship to John Nolan by National Children’s Research Centre, Crumlin Hospital. ncrc

References:

  1. Davidoff, A. M. Neuroblastoma. 2012 Semin. Pediatr. Surg. 21, 2–14.
  2. Piskareva, O., Stallings, R. Neuroblastoma. In: Epigenetic Cancer Therapy edited by Grey S., Elsevier 2015.
  3. Conlon, R., Analysis of microRNA bearing exosomes in models of drug resistant neuroblastoma. PhD Thesis. Dublin: Royal College of Surgeons in Ireland; 2015.
  4. Piskareva, O., Harvey, H., Nolan, J., Conlon, R., Alcock. L., Buckley, P., Dowling, P., O’Sullivan, F., Bray, I., Stallings, T.L. The development of cisplatin resistance in neuroblastoma is accompanied by epithelial to mesenchymal transition in vitro. 2015 Cancer Letters, 364:142-55.

Reported by Olga Piskareva