CSM hosts a guest scientist from Brazil

http://www2.bioqmed.ufrj.br/ldn/matthias.htmlIn May 2015, the Department of Physiology and Medical Physics and CSM was pleased to host a guest scientist from the Instituto de Bioquímica Médica from the Universidade Federal do Rio de Janeiro in Brazil. Supported by RCSI through SFI/ISCA funding Prof. Gralle worked with Dr. Koenig in conjunction with Dr. Duessman and Prof. Prehn on the implementation of models for localised application of toxins relevant in Alzheimer’s disease and analysed their impact on sub cellular structures (05/05/2015-17/05/2015).

Congratulations to Dr Alice O’Farrell

Congratulations to Dr Alice O’Farrell (Physiology & Medical Physics & Centre for Systems Medicine) who was awarded the 2015 Royal Academy of Medicine in Ireland (RAMI) Barcroft Medal at the Annual Meeting of the Biomedical Sciences Section, which was held at RCSI on June 18th. The Award was made for Alice’s presentation entitled “Cardiac Metabolic Pathway Remodelling in Response to Sunitinib Malate: Potential Role for Positron Emission Tomography in the Cardio-Oncology Setting”.

Congratulations to Dr. Amanda Tivinan

Congratulations to Dr. Amanda Tivinan who has been made Patron of the West Wicklow Cancer Support Group, in addition to setting up the IBTRI (Irish Brain Tumour Research Initiative) a platform for BT researchers throughout Ireland to liaise and collaborate, with future fund raising potential to benefit research here in RCSI.

Her recent publication was published in the Frontiers in Neuroscience journal http://journal.frontiersin.org/article/10.3389/fnins.2015.00218/abstract

The Centre for Systems Medicine welcomes: Dr. Michael Courtney Turku Centre for Biotechnology, Finland.

Lecture entitled “NOS1AP, an adaptor protein linked to neurological diseases, reveals a novel signalling paradigm”

Venue: Albert L.T. 4pm 11th June 2015

Michael Courtney leads a research group focused on neuronal signaling mechanisms and is currently based at the Turku Centre for Biotechnology, Turku, Finland.

Research: After early investigations of the roles of
JNK signalling in neuronal death and development his group focused on
identifying targetable mechanisms by which NMDA receptor signaling influences
neuronal cell fate via activation of the p38MAPK pathway. One of the major NMDA
receptor pathways regulating p38MAPK involves the ternary complex of NMDA
receptor, PSD95 and nNOS. The lab demonstrated that PSD95/nNOS-dependent
pathways could be inhibited by nNOS-derived peptides, resulting in
neuroprotection. They showed that NMDA receptor activity leads to recruitment
of NOS1AP to nNOS and demonstrated that NOS1AP is required for NMDA-evoked
stress-activated MAPK responses and downstream excitotoxic consequences. They
developed a selective inhibitor peptide of the interaction between NOS1AP and
nNOS, with neuroprotective properties in cell cultures and in vivo (in a
preclinical model of perinatal asphyxia). More recently they identified that
interaction of nNOS with NOS1AP involves an unexpectedly complex interplay
between two distinct interaction sites. Each site is potentially druggable,
thereby providing increased opportunities for therapeutic intervention. This is
of potential interest considering that the NR-PSD95-nNOS complex and
potentially the recruitment of NOS1AP may be involved in some of the most
common causes of death and disability from stroke to neuropathic pain,
depression and anxiety disorders, while NOS1AP has been genetically linked to
schizophrenia, post-traumatic stress disorder, sudden cardiac death and long QT
syndromes. http://www.btk.fi/research/affiliated-groups/courtney-michael-neuronal-signal-pathways

All welcome to attend,

Jochen Prehn


Title: Sox2, more than a transcription factor Speaker: Dr. Pengyan Xia

Dr. Pengyan Xia

Sox2, more than a transcription factor

Date: Thursday 30thApril 2015

Dear Colleagues,

The Centre for Systems Medicine is pleased to announce another speaker of our seminar series, Dr Pengyan Xia.

Dr Xia’s research is focussed on
studying development and differentiation of the haematopoietic system, in
particular in self-renewal of haematopoietic stem cells (HSCs) and anti-microbe
activity of white blood cells that derived from HSCs. Specifically, his
research is focussed on signalling platforms that regulate the
self-renewal of HSCs (Xia et al, J Exp Med 2014) as well as extracellular
DNA triggered innate immunity in neutrophils (Xia et al, Nat Immunol 2015).

You are all very welcome to attend, please register at:csm@rcsi.ie


Markus Rehm

Centre for Systems Medicine, Department of Physiology and Medical Physics

Royal College of Surgeons in Ireland

Funded by the International Strategic Cooperation
Award (ISCA) Grant Number SFI/13/ISCA/2845 China

MEL-PLEX Worshop Wednesday 6th May 2015

Innovative Approaches in Translational Melanoma Research

MEL-PLEX is a Marie Skłodoswska-Curie
Innovative Training Network funded by Horizon 2020 aiming to train a new
generation of researchers that can navigate confidently between clinical,
academic and private sector environments. As part of its training programme,
MEL-PLEX will hold a training course which will consist of workshop to provide
an overview of the current status of malignant melanoma management and the
field of translational cancer systems biology and systems medicine, followed by
a Transferable Skills course to introduce the new PhD students to basic topics
in scientific research.

The main topics addressed

  • Melanoma
    pathology and treatment
  • Melanoma
    proliferation and migration
  • Kinase
    cascades in melanoma
  • Cell
    death modalities in melanoma
  • Biomarker
    identification and validation
  • Targeted
    drugs and drug development
  • Innovative
    experimental models
  • Applied
    Systems Biology
  • Systems
    Medicine strategies

The workshop entitled “Innovative
Approaches in Translational Melanoma Research” is an open event. Deadline for
registration is April 24th 2015.

For more information and free
registration please contact: melplexETN@rcsi.ie

Venue: Cheyne Lecture Theatre, RCSI, 9am
Wednesday 6th May 2015

Seminar: “Systems pharmacology and pharmacokinetic/pharmacodynamic modelling Oncology”

The Centre for
Systems Medicine is delighted to announce
distinguished  speakers to its 2015 seminar series:

Prof. Donald Mager
, Associate Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York (UB) 
Bio: -http://pharmsci.buffalo.edu/CEPKPD/faculty/MAGER.HTML


Prof.Robert Straubinger, Professor of Pharmaceutical
at University at Buffalo School of Pharmacy.

Bio: -http://pharmsci.buffalo.edu/CEPKPD/faculty/STRB.HTML

Houston Lecture Theatre, RCSI, 4.30 Pm Tuesday 10th March 2015


Congratulations to Dr. Lorna Flanaghan on winning a poster prize at the The Irish Association for Cancer Research 2015 meeting


L.Flanagan, S.Curry, M. Meyer, J. Fay, O. Bacon, E.W. Kay, D.A. McNamara, and J.H.M. Prehn

‘’We examined the role of executioner caspases in tissue regeneration following chemotherapy.Exploiting and antagonising this paracrine role of executioner caspases may be an interesting, novel approach for the treatment of tumours characterised by
resistance and relapse. Our data highlight that inhibition of Caspase-3, or
antagonising downstream effectors of Caspase-3 paracrine signalling, may
represent a novel approach to halt, or at least impede, tumour cell repopulation
following chemotherapy’




A systems biological analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.

The protease caspase-9 is activated on the apoptosome, a multi-protein signal transduction platform that assembles in response to mitochondria-dependent apoptosis initiation. Despite extensive molecular research, the assembly of the holo-apoptosome and the process of caspase-9 activation remain incompletely understood. Here we therefore integrated quantitative data on the molecular interactions and proteolytic processes during apoptosome formation and apoptosis execution, and conducted mathematical simulations to investigate the resulting biochemical signalling, quantitatively and kinetically.

Interestingly, when implementing the homo-dimerisation of procaspase-9 as a prerequisite for activation, the calculated kinetics of apoptosis execution and the efficacy of caspase-3 activation failed to replicate experimental data. In contrast, assuming a scenario in which procaspase-9 is activated allosterically upon binding to the apoptosome backbone, the mathematical simulations quantitatively and kinetically reproduced all experimental data. These data included a XIAP threshold concentration at which apoptosis execution is suppressed in HeLa cervical cancer cells, half-times of procaspase-9 processing, as well as the molecular timer function of the apoptosome.

Our study therefore provides novel mechanistic insight into apoptosome-dependent apoptosis execution and suggests that caspase-9 is activated allosterically by binding to the apoptosome backbone. Our findings challenge the currently prevailing dogma that all initiator procaspases require homo-dimerisation for activation.

J Biol Chem. 2014 Aug 8. pii: jbc.M114.590034. [Epub ahead of print]

A systems biological analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.

Würstle ML(1), Rehm M(2).

Author information:

(1)Royal College of Surgeons in Ireland, Ireland.

(2)Royal College of Surgeons in Ireland, Ireland mrehm@rcsi.ie