Version 2
Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
PhD Project Template



Use one form per project
Please complete & submit to international@nuigalway.ie as soon as possible, and by 27/11/2012
In your email, begin the subject line with [SWB] (be sure to use square brackets) to ensure that
your email is filed correctly. Emails will be automatically filed
PI name & contact details:
Dr. Eva Szegezdi
School:
School of Natural Sciences
Has project been agreed with head (or
nominee) of proposed registration school?
Research Centre / group affiliation:
Apoptosis Research Centre/TRAIL Research Group
Research group / centre website:
www.apoptosis.ie
PI website / link to CV:
http://www.apoptosis.ie/szegezdi.html
Brief summary of PI research / research group / centre activity (2 or 3 lines max):
If you are already involved in relevant scholarly activities relating to Brazil, please mention them here.
The aim of the Apoptosis Research Centre is to create a focused, interactive and dynamic research
environment, where researchers can come together to understand the complex pathways leading to
cell death and can apply this knowledge to the discovery of novel therapies for the treatment of a
wide ranges of diseases.
Title & brief description of PhD project (suitable for publication on web):
Development of novel drugs for activating death receptor-mediated killing of tumours
Cytokines of the Tumour Necrosis Factor (TNF) family, especially the so called death ligands (TNF,
TRAIL, FasL) are being considered for treating cancer since their discovery. Their utility is however
hampered because of either toxic side effects (for TNF and FasL) or low potency due to the NF-kBmediated inflammatory response they also induce (TRAIL, TNF). Activation of NF-kB drives the
expression of anti-apoptotic genes and secretion of cytokines and chemokines promoting tumour drug
resistance, invasiveness and metastasis. The final biological response (cell death or inflammation) is
determined by the complement of the adaptor proteins recruited to the activated death receptor.
Our laboratory, as well as other groups, have found that inhibition of NF-kB or the deficiency of the
adaptor protein, TRAF2, involved in TRAIL-mediated NF-kB activation, can sensitise tumour cells to
TRAIL-induced apoptosis. Based on these results the purpose of the current proposal is to develop
Version 2
Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
inhibitors that can disrupt the recruitment of TRAF2 to the TRAILR-DISC to uncouple TRAILmediated inflammatory signalling from cell death signalling. Recent discoveries on the mechanism of
signal transduction by the founding member of the family, TNF and the development of new
formulations of recombinant TNF reopened the opportunity to use TNF for cancer therapy. These
results indicate that disruption of the TRADD-TRAF2 interaction can have a major influence on
TNF-mediated tumour cell eradication as well. The will examine this possibility and determine
whether blocking the recruitment of TRAF2 to the TNFR-DISC can prevent TNF-mediated
inflammatory and proliferative signalling and promote TNF-mediated cell death. For the studies, cell
lines engineered to express TRADD-binding deficient TRAF2 or TRAF2-binding deficient TRADD
will be utilised. These studies will assess whether TRADD-TRAF2 interaction inhibitors have a
broad therapeutic potential and provide important data to for the development of the identified
inhibitors into lead molecules.
Unique selling points of PhD project in NUI Galway:
The graduate student studying this project will gain a broad spectrum of scientific experience in the
fields of: molecular and cell biology, drug design, bioinformatics with an insight to
commercialisation to pursue a future translational or industry-linked research career.
The student will join a structured PhD training programme with an opportunity to attend specialised
classes such as molecular and clinical cancer biology, journal clubs, statistics and scientific writing to
prepare postgraduate students for their careers ahead. The structured PhD training involved annual
appraisal and mentoring to support the career development of the student.
The student will regularly attend international conferences to broaden their knowledge and meet with
the leaders of the scientific community.
The graduate student will also gain experience in a wide range of state-of-the-art technologies,
including computational drug design, protein structural studies, flow cytometry, live confocal
microscopy, as well as most standard molecular and cell biology techniques.
The candidate will join the Apoptosis Research Centre where 7 renowned research groups with a
broad range of international collaborations and industry connections collaborate.
Name & contact details for project queries, if different from PI named above:
Please indicate the graduates of which disciplines that should apply:
Biochemistry,
Chemistry
Genetics
Molecular biology
Pharmacology
Cell Biology
Medicine
and related disciplines
Version 2
Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
Ciência sem Fronteiras / Science Without Borders Priority Area:
Please indicate the specific programme priority area under which the proposed PhD project fits- choose only
one (tick box):
Engineering and other technological areas
Pure and Natural Sciences (e.g. mathematics, physics, chemistry)/Physical Sciences (Mathematics,
Physics, Chemistry, Biology and Geosciences)
Health and Biomedical Sciences / Clinical, Pré-clinical and Health Sciences
X
Information and Communication Technologies (ICTs), Computing
Aerospace
Pharmaceuticals
Sustainable Agricultural Production
Oil, Gas and Coal
Renewable Energy
Minerals, Minerals Technology
Biotechnology
Nanotechnology and New Materials
Technologies for Prevention and Mitigation of Natural Disasters
Bioprospecting and Biodiversity
Marine Sciences
Creative Industry
New technologies in constructive engineering
Please indicate which of the following applies to this project (referring to Science Without Borders
arrangements):
Suitable only as a Full PhD (Y/N):
Available to candidates seeking a Sandwich PhD arrangement (Y/N):
Suitable for either/Don’t know: __Y___