Common Gut Bacterium Associated with Colorectal Cancer

HRB-funded research in the Centre for Systems Medicine could lead to a new biomarker for colorectal cancer.

New evidence that a common gut bacterium is involved in colorectal cancer has been published by researchers in the Centre for Systems Medicine, RCSI (first author is Dr Lorna Flanagan and study PI is Dr David Hughes). The manuscript* is currently available online in the European Journal of Clinical Microbiology & Infectious Diseases.

The HRB funded research found a significantly increased presence of a common microbe Fusobacterium nucleatum (Fn) in tissue and stool samples of patients with colorectal cancers and colorectal adenomas. Additionally Fn infection levels were related with adenoma progression from early to advanced stages and the transition from an adenoma to cancer, highlighting the potential of Fn detection as a possible indicator of colorectal cancers. The research further found that cancer patients with low bacterial levels had significantly longer survival times than patients with moderate and high levels of the bacterium.

The research suggests that screening for Fn levels may be used as a new colorectal cancer detection method or to further inform existing screening strategies. Efforts to combat Fn infection could be considered for colorectal cancer patients with high levels of the bacterium to improve the survival prospects for these patients. Fn levels may be used to classify adenomas that may have a higher risk of disease progression to colorectal cancers with implications for increasing follow-up and at the possible use of anti-microbial treatments. Potentially, any impact of Fn infection on adenoma development and progression to more serious stages will be considerable, because 95% of all colorectal cancers arise from adenomas, but only a small number of them become cancerous. Currently, there are no reliable predictive markers of whether an adenoma will advance to cancer.

Seminar by Prof. Borner on use of viruses and funghi in apoptosis research

The Centre for Systems Medicine is pleased to announce another speaker to our seminar series,

Prof Dr Christoph Borner

Professor in Medical Cell Research, Institute of Molecular Medicine,
Albert Ludwigs University Freiburg, Germany

Use of viruses and funghi to uncover novel apoptosis signaling pathways

The primary interest of his laboratory is the elucidation of the function of multidomain anti- and pro-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL, Mcl-1, Bax and Bak), the characterization of components of caspase-independent and RNA-virus (SFV)-induced apoptosis signaling, and the mathematical modelling of apoptotic and mitogenic FasL signaling pathways in primary hepatocytes.

Find more details on his homepage.

Recent publications:

  • A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus-Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis. El Maadidi S, Faletti L, Berg B, Wenzl C, Wieland K, Chen ZJ, Maurer U, Borner C. J Immunol. 2014 Jan 3.
  • Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK. Geissler A, Haun F, Frank DO, Wieland K, Simon MM, Idzko M, Davis RJ, Maurer U, Borner C. Cell Death Differ. 2013 Oct;20(10):1317-29. doi: 10.1038/cdd.2013.78. Epub 2013 Jul 5.
  • TNFα-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation. Huai J, Vögtle FN, Jöckel L, Li Y, Kiefer T, Ricci JE, Borner C. J Cell Sci. 2013 Sep 1;126(Pt 17):4015-25. doi: 10.1242/jcs.129999. Epub 2013 Jun 20.
  • Non-canonical function of Bax in stress-induced nuclear protein redistribution. Lindenboim L, Ferrando-May E, Borner C, Stein R. Cell Mol Life Sci. 2013 Aug;70(16):3013-27.

The talk is open to everyone and will be held in Houston Lecture Theater, RCSI on 28th of January 2014 at 1:30 pm.

Seminar by Lou Philipson: New Insights into Insulin Secretion

The Centre for Systems Medicine is pleased to announce another speaker to our seminar series,

Prof. Lou Philipson,
Professor of Medicine, Director, Kovler Diabetes Center, The University of Chicago

New Insights into Insulin Secretion

Louis Philipson, MD, PhD, is an endocrinologist and a leading world authority on diabetes mellitus. His clinical interests include type 1 diabetes, complicated type 2 diabetes, monogenic diabetes and hypoglycemia.

Recognized for unmatched expertise in the treatment of diabetes that is difficult to manage, Dr. Philipson’s multisciplinary team frequently accepts referrals and provides consultations. Under his leadership, Kovler Diabetes Center has been recognized as a one of only seven National Institutes of Health (NIH) Diabetes Research and Training Centers in the U.S.

For more than 25 years, Dr. Philipson has tirelessly explored the biophysical, molecular and genetic aspects of insulin secretion, and the genetics of diabetes. He and his colleagues discovered rare insulin gene mutations that produce beta cell ER stress and, in turn, cause neonatal diabetes.

In addition, Dr. Philipson and his colleagues are among the nation’s leading experts on monogenic diabetes, following more than 100 patients diagnosed with neonatal diabetes and many others with maturity onset diabetes of the young (MODY) type diabetes. He also serves as co-director of the Human Islet Transplantation project at the University of Chicago.

Dr. Philipson has served as principal investigator on numerous research projects. His work is widely published in biomedical journals, including the Proceedings of the National Academy of Sciences, Science, Nature, Diabetes, American Journal of Physiology and the Journal of Biological Chemistry.

http://www.uchospitals.edu/physicians/louis-philipson.html

The talk is open to everyone and will be held in Houston Lecture Theater, RCSI on the 16th of January 201 at 4:30 pm.

Irish Cancer Society Research Fellowship awarded to Amanda Tivnan

Congratulations to Dr. Amanda Tivnan from the Centre for Systems Medicine, Royal College of Surgeons in Ireland. She is awarded a Research Fellowship by the Irish Cancer Society.

AmandaTivnan receives Irish Cancer Society Research Award

Dr Amanda Tivnan with Professor John Fitzpatrick, Head of Research, Irish Cancer Society, Mr Dermot Breen, Tesco, and Ray D’Arcy, Broadcaster at Today FM receiving the Irish Cancer Society Research Fellowship Award Certificate

Dr. Amanda Tivnan at the Irish Cancer Society Research Fellows and Scholars Awards Ceremony in Dublin at which six new cancer research grants were awarded, said, “Although any form of brain cancer is serious, diagnosis of a patient with glioblastoma multiforme (GBM) currently holds the worst outcome, with an average survival of only 12-15 months. It is a highly aggressive brain cancer due to increased numbers of ‘pumps’, called transporters, on the cancer cells surface that rapidly remove the chemotherapy from the cell, not allowing it enough time to act and kill the brain cancer.”

“My research aims at targeting these pumps, so allowing the chemotherapy a longer time within the cancer cells and hopefully increasing its killing abilities. It will also focus on developing novel technologies to remove these pumps from the cancer cells, and then reassessing the response of these glioblastoma cells to chemotherapy, providing us with hope for patient survival in the future.”

Speaking at the Ceremony, Prof. John Fitzpatrick, Head of Research, Irish Cancer Society said, “The Irish Cancer Society’s vision for cancer research is based on achieving world-class discoveries across all cancer types to improve outcomes for the thousands of patients that are diagnosed each year in Ireland. We are extremely proud to announce our next round of Fellows and Scholars that will join the battle against cancer by applying their great knowledge and skills- to finding new ways to improve patient outcomes.”

“Over the past 50 years, the Irish Cancer Society has contributed €33 million to advance high-quality cancer research in Ireland. This funding has gone towards research grants, such as the Scholarship and Fellowship programmes, and the country’s first Collaborative Cancer Research Centre BREAST-PREDICT, which aims to predict the best treatment options for breast cancer patients. None of this would have been made possible without the general public’s ongoing support and commitment to fundraising for cancer research.” The Society’s Fellows and Scholars are also supported by the Tesco Charity of the Year Partnership 2010-2011 and the Movember Foundation.

Women race to pay tribute to friend who died of brain cancer and raise almost €30K for Irish Cancer Society research grants

An inspiring group of 47 women self-titled the Rainbow Runners raced to the finish line at the Flora Women’s Mini Marathon this year to pay tribute to their dear friend Gayle Warnock, who died from an inoperable brain tumour in 2012 aged 38, and raised almost €30K for Irish Cancer Society Research.

Caroline Reay said the women had chosen the Irish Cancer Society “as Gayle wanted to run the marathon herself, and donate the money to the Society to encourage new research discoveries that might one day benefit thousands of patients battling cancer in Ireland.” Their contribution will go towards the Irish Cancer Society’s total €33 million investment in cancer research over the past 50 years, making them Ireland’s largest voluntary funder of cancer research.

The Society’s Research Fellows and Scholars awards are designed to foster home-grown cancer research talent in Ireland and to ensure new research projects are commenced in a range of cancers including brain tumours, colorectal, oesophageal, prostate and breast cancers. The research projects span a wide range of research areas and will investigate a number of potentially important topics, such as novel technologies that could increase the length of time that chemotherapy can act inside cancer cells, novel targets to develop drugs against and broadening treatment options.

Workshop on light sheet fluorescence microscopy was full success

CSM successfully hosted the first Irish/UK light sheet fluorescence microscopy workshop organized by Dr Emmanuel G. Reynaud (UDC) and Dr Heiko Dussmann (RCSI). Lectures given by Malte Wachsmuth (21st Nov 2013), Bill Chaudry, Chris Power, Ellen Barker, and Emmanuel Reynaud drew a clear picture in the morning sessions (25th Nov 2013) of the new dimensions of imaging possibilities, which were then demonstrated in the hands on training sessions in the afternoon.

Thank you to the speakers agreeing to offer presentations for download:

Here are some impressions of the event:

Seminar: Fiona Ginty, GE Global Research Centre

Dr. Fiona Ginty

Principal Scientist, Life Sciences and Molecular Diagnostics, General Electric Global Research Center

Tumor heterogeneity revealed using high-order in situ multiplexing

The Centre for Systems Medicine is pleased to announce a seminar by Dr. Fiona Ginty from General Electric Global Research Center, Niskayuna, NY.

Abstract: Protein analysis in formalin-fixed, paraffin-embedded tissues is typically limited to 1-2 markers per tissue slide using chromogenic stains, or up to four markers using immunofluorescence. The increasing demands on tissue for predictive and prognostic biomarker testing presents significant challenges for pathologists and oncologists to ensure that the most important markers are selected for patient care. Coupled with this, tumor and cellular heterogeneity may confound genomic results. To address these challenges, GE scientists have developed a multiplexed immunofluorescence technology that allows measurement of up to 60 markers at single cell level in a 5 um FFPE tissue section (MultiOmyx™). DNA FISH analysis may also be conducted on the same sample, following multiplexed protein analysis. Image processing and visualization tools allow interactive assessment cellular biomarkers in context of tumor histology and microenvironment.  In addition to sparing precious sample, multiplexed analysis allows quantitation and visualization of extensive biomarker heterogeneity within the tumor, stroma, blood vessels and other cellular features. This platform will provide new opportunities for redefining and understanding biological mechanisms for basic and drug discovery research.

Please see also the publication Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue PNAS 2013 110 (29) 11982-11987; published ahead of print July 1, 2013

The talk is free and open to everyone and will be held in Houston Lecture Theater, RCSI on the 16th of December 2013 at 4 pm.

This seminar is supported by the RCSI seed fund program.

Seminar: Real-Time Near Infrared Fluorescence Imaging

Prof. Donal O’Shea

Head of the Department of Pharmaceutical and Medicinal Chemistry,
Royal College of Surgeons in Ireland

Real-Time Near Infrared Fluorescence Imaging – from chemistry to mice and the potential for beyond

Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for the investigation of fundamental biological processes.  It also offers huge future potential for human imaging coupled to therapeutic procedures such as fluorescence guided surgery. We have recently developed a new class of near infrared (NIR) fluorophore from which excellent in vitro and in vivo imaging probes can be developed.1 But in spite of the advantages offered by longer wavelength NIR emissions a common limitation with fluorescence imaging is the difficulty in discriminating non-specific fluorescence from fluorescence localized at a specific region of interest. This can restrict imaging to individual time points at which non-specific background fluorescence has been minimized.  It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events as this would permit imaging of such events in real time without background interference. Two approaches (one molecular and one nanoparticle based) to achieve this using cellular endocytosis as the NIR-fluorescence switching trigger will be described.2  Both approaches permit continuous real-time imaging of the cellular uptake, trafficking and efflux processes as extracellular fluorophore is non-fluorescent. The principles behind the NIR-fluorescence off/on switching will be explained and illustrated in vitro and in vivo. In addition, a theranostics approach using the combination of NIR fluorescence imaging and photodynamic therapy will also be shown.3

Please feel welcome to attend on the 6th of December 2013 at 9:10 am. The talk will be held in Cheyne Lecture Theatre at RCSI, St. Stephen’s Green.

1.         (a) Tasior, M.; O’Shea, D.F. Bioconjugate Chem. 2010, 21, 1130. (b) Wu Dan, O’Shea D.F. Org. Lett. 2013, 15, 3392.

2.         (a) Palma, A.; Alvarez, L.A.; Frimannsson, D.O.; Grossi, M.; Quinn, S.J.; O’Shea, D.F. J. Am. Chem. Soc. 2011, 133, 19618. (b) http://www.youtube.com/watch?v=FjipbGTf8w4.

3.         O’Connor, A. E.; McGee, M. M.; Likar, Y.; Ponomarev, V.; Callanan, J. J.; O’Shea, D. F.; Byrne, A. T.; Gallagher, W. M. Intern. J. Cancer, 2012, 130, 705.

 

Workshop: Light sheet fluorescence microscopy

Date: Monday 25th of November
Venue: Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin 2
Organisers: Dr Emmanuel G. Reynaud (UCD), Dr Heiko Dussmann (RCSI), Dr Chris Power (Zeiss)

Light sheet microscopy is an emerging technology that enables long term imaging of large biological specimen with minimal photo damage. It opens new avenues to study cell biological and developmental processes with unprecedented resolution in space and time and facilitates systems biology approaches by quantitative imaging of entire living systems. The life science research community is eager to use light sheet microscopy inspired by the many spectacular proof of principle papers, but is less aware of the technological and computational challenges associated with the light sheet microscopy paradigm.

Schedule: Monday 25th of November
Morning (9-12 am): Open to all

Introduction: Dr Emmanuel G. Reynaud (UCD), Dr Heiko Dussmann (RCSI)

  • Dr Bill Chaudhry, Newcastle University:Introduction to Light Sheet Microscopy
  • Dr Chris Power, Carl Zeiss UK: Zeiss Light Sheet Z-1
  • Ellen Baker, Hamamatsu: “Cameras fro Light Sheet Microscopy”
  • Dr Emmanuel G. Reynaud, University College Dublin: Challenges in Light Sheet Microscopy

Lunch-time:  3 quick introductions to the Zeiss Lightsheet Z-1

Afternoon (1pm- 5pm): three groups of 5 persons.

  • Session 1: Sample preparation, Dr Emmanuel G. Reynaud
  • Session 2: Light Sheet Z.1, Dr Chris Power and Dr Heiko Dussmann
  • Session 3: How to build a light sheet microscope, Dr Bill Chaudhry
  • Last session: Data management, Dr Chris Power and Dr Emmanuel G. Reynaud

Evening (5pm- 7pm): Discussion and Q&A

Registration:
Send application requests to microimaging@rcsi.ie with a short description of your research/needs for 3D microscopy.

Fees:
A small fee (20€) will apply to cover room rental and consumables. A 50% discount will apply for MSI and RMS members.

Further training options:
Demonstrations: Besides the workshop, there will be demo time slots available during the week after the 25th of November, if you are interested please contact Dr Chris Power (via email Chris.Power@zeiss.com) and include a brief description of your potential own sample you want to image.

Training sessions: We will run two additional training sessions depending on numbers and requests.
Date: 21st of November 1.30 pm-5 pm

  • Session: Cell Biology and Tissue Engineering (10 persons max.)
  • Dr Malte Wachsmuth, EMBL: “Observing single molecules with a light-sheet microscopeTalk free for all, more details here

Date: 2nd of December 1.30 pm-5 pm

  • Session: Extra class


Accommodation:

Hotels in close proximity: St. Stephen’s Green Hotel, Travelodge and Albany House
We might be able to arrange for corporate rates, please contact us for more information.

Low-Budget: Avalon House is a hostel just down the road from the conference venue. Rooms range from single bedrooms to large dorms. Prices start from 12 EUR; if it happens to be your birthday, you might get a bed for free!

Sponsors:

Download flyer here

Seminar: light sheet microscopy

Dr. Malte Wachsmuth

Cell Biology & Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

Observing single molecules with a light-sheet microscope

As part of the workshop on light sheet fluorescence microscopy, the Centre for Systems Medicine is pleased to announce a seminar about this thriving imaging technique. Dr. Wachsmuth performed his PhD research at the Division Biophysics of Macromolecules, German Cancer Research Center (DKFZ) in 2002 and gained several years of expertise in imaging techniques working for Leica Microsystems, University of Heidelberg, and as group leader of the Cell Biophysics Group, Institut Pasteur Korea, Seoul, South Korea. Since 2007 he is scientist in the Cell Biology & Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg.

In his current research, Dr. Wachsmuth and his team focus on extending and integrating imaging modalities, building new instrumentation for visual biochemistry and the structure and dynamics of the cell nucleus.

More information can be found on his research homepage.

The talk is free and open to everyone and will be held in Newman Study, RCSI on the 21st of November 2013 at 2 pm.

More information about the workshop is available here.

A tool for predicting drug-specific cell death responses in melanoma

Markus Rehm and his team published a new study in the Journal “Cell Death and Differentiation” (Cell Death Differ. 2013 Nov;20(11):1521-1531). In this study, they were successful in predicting the best treatment option for individual melanoma cell lines by using a novel systems modelling approach. The elimination of cancer cells by a process called Apoptosis is a mainstay of anti-cancer chemotherapies. Markus Rehm and his team used quantitative data of proteins that regulate this cell death mechanism together with information on their interactions and regulatory functions to predict the treatment outcome for individual cell lines to different apoptosis-inducing drugs. Using these information they were able to select the best treatment option in up to 91% of the cases. Additionally, the investigators could identify optimal co-treatment strategies to overcome resistance in melanoma cells. Their novel approach may contribute to the development of personalized cancer treatments in the future.

The systems model was co-developed and implemented by Dr Maximilian Würstle, a postdoctoral researcher in the group of Dr Rehm. A poster designed by Dr Würstle won the “best poster” price at the European Cell Death Organisation annual conference in Paris in late September. Oral presentations of the study results were given in guest seminars and conference talks in recent months (Dermatology Clinics, University of Dresden; Mount Sinai School of Medicine, New York; 3U Cancer Conference, Dublin; CSHL Cell Death meeting, Cold Spring Harbor).