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Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
PhD Project Template
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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:
School:
Dr. Michael P. Carty
Michael.carty@nuigalway.ie
School of Natural Sciences, Biochemistry, NUI Galway
Has project been agreed with head (or
nominee) of proposed registration
school?
yes
Research Centre / group
affiliation:
Research group / centre
website:
Centre for Chromosome Biology
DNA Damage Response laboratory, Centre for Chromosome
Biology
http://www.chromosome.ie/researchers/carty/
PI website / link to CV
http://www.nuigalway.ie/biochemistry/staff/carty/index.html
Brief summary of PI research / research group / centre activity (2 or 3 lines max):
The main aim of the DNA Damage Response group led by Dr. Carty is to elucidate the molecular
basis of the response of human primary cells and cancer cells to DNA damaging agents, including
carcinogens such as UV radiation, and cancer therapeutics, in particular platinum-based drugs and
ionizing radiation.
Title & brief description of PhD project (suitable for publication on web):
The role of long-wavelength ultraviolet A (UVA) radiation in melanoma development.
Basal and squamous cell carcinoma are the most common forms of skin cancer, melanoma arising
from pigment-producing melanocytes is the most dangerous form of this disease and accounts for
the majority of skin cancer-related deaths. Exposure to ultraviolet (UV) radiation is a major risk
factor for skin cancer development. The UV spectrum is divided into UVC (200-280nm), UVB (280320nm) and UVA (320-400nm). Depletion of the ozone layer has increased the level of DNA
damaging shorter wavelength UV radiation reaching the earth’s surface. However, 90% of the
incident UV radiation is in the long wavelength UVA range. There is strong evidence that exposure
to long-wavelength UVA radiation is particularly associated with melanoma development, in part
because UVA radiation can reach melanocytes located in the epidermal layer of the skin. While the
relationship between UVB radiation-induced DNA damage and skin cancer development is relatively
well understood, the molecular basis of the link between UVA exposure and melanoma
development is still not clear. It is important to understand the effects of UVA radiation on the
main target cell, the primary melanocyte that ultimately give rise to melanoma.
To investigate this process, we have developed cell culture systems in which to investigate the
effects of UVA radiation on normal human epithelial melanocytes (NHEM), and have shown that
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Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
UVA activates key DNA damage responses and the cell cycle checkpoint protein Chk1 in NHEM.
The role of DNA damage-activated signalling by the checkpoint kinase Chk1 in modulating the
response of primary melanocytes to UVA will be investigated using small molecule inhibitors of
Chk1, and siRNA approaches, and biochemical approaches to identify substrates of Chk1 in NHEM.
To identify key pathways that modulate the initial response of normal melanocytes to UVA
radiation, qPCR-based analysis of UVA-induced gene expression, and proteomics-based screening
will be used. Selected genes will be chosen for further study using cellular, genomic and
biochemical approaches, to determine the role of key NHEM genes in regulating cell proliferation,
apoptosis, genome stability and cell transformation in response to UVA radiation.
The status of key pathways in melanoma cell lines and in melanoma tissues will also be investigated.
This research focuses on an important area at the interface of environmental change and health,
and builds on our ongoing research into the effects of ultraviolet radiation on human cells (1-3).
This research will provide training in cell biology, genomics, proteomics and cancer biology, and will
provide molecular targets that may be of value in developing novel therapies and diagnostics for
melanoma.
See related references
1.
2.
3.
Glynn et al., DNA Repair 5, 491-504 (2006)
Flanagan et al. Int. J. Mol. Med. 19, 589-596 (2007)
Cruet-Hennequart et al. Subcell. Biochem. 50, 189-209 (2010) Review
Unique selling points of PhD project in NUI Galway:
State-of-the-art facilities are available in Biochemistry, the Centre for Chromosome Biology,
including cell culture facilities, dedicated long wavelength UVA-irradiation facilities, flow cytometry,
fluorescence microscopy with live cell imaging, and systems for gene and protein analysis. Highlevel training in the use of all equipment, procedures and data analysis will be provided.
Students will be part of the structured PhD programme in Biochemistry in the School of Natural
Sciences, focused on Biochemistry. As part of this programme, in addition to the research thesis,
students take a series of focused modules aimed at developing core professional skills and
knowledge in areas relevant to future career development.
The DNA Damage Response group has a strong record of graduating PhD students, and in research
publication.
This is a highly interdisciplinary project carried out in the DNA Damage Response laboratory as part
of the Centre for Chromosome Biology, a network of 11 research groups with high-level expertise in
all aspects of chromosome biology. Students will have opportunities to present their results in the
weekly seminar series of the Centre for Chromosome Biology where feedback from faculty and
researchers directly working in the field provides an invaluable learning experience. Biochemistry
and the Centre for Chromosome Biology host a strong seminar programme, where invited national
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and international research leaders present their latest results.
Interactions with colleagues in the Environment and Health group of the Martin Ryan Institute at
NUI Galway will also be developed. There are ongoing links with international centres, including the
Beatson Institute, Glasgow, Scotland, in the investigation of UVA responses in mouse melanocytes.
Name & contact details for project queries, if different from PI named above:
Please indicate the graduates of which disciplines that should apply:
Biochemistry, Biotechnology, Molecular Biology, Cell Biology
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): _ n (collaboration could also be considered)
Available to candidates seeking a Sandwich PhD arrangement (Y/N): __y___
Suitable for either/Don’t know: ___y__