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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:
Dr. Heinz Peter Nasheuer,
Biochemistry,
National University of Ireland, Galway
University Road
Galway
Ireland
Email: h.nasheuer@nuigalway.ie
phone: +353-91-49 2430
fax: +353-91-49 5504
School:
School of Natural Sciences
Has project been agreed with head (or
nominee) of proposed registration school?
Research Centre / group affiliation:
Research group / centre website:
PI website / link to CV:
Centre for Chromosome Biology;
Cell Cycle Control Group
http://www.chromosome.ie/researchers/nasheuer/
http://www.chromosome.ie/researchers/nasheuer/
Brief summary of PI research / research group / centre activity (2 or 3 lines max):
The research group has three major topics of interest:
 Cell cycle-dependent regulation and mechanisms of human DNA replication and repair pathways
 Protein-protein interaction studies in living cells using advanced microscopy techniques
 Systems biology of protein-protein interactions in living cells
Title & brief description of PhD project (suitable for publication on web):
Complex formation, mobility and concentration of DNA replication and DNA repair proteins in
the cell cycle and after DNA damage
The high fidelity and the tight regulation of DNA replication and DNA repair processes in the cell
cycle and after DNA damage is essential for the stability of the human genome. Failures of these
processes will yield mutations of chromosomal DNA or changes in the numbers of chromosomes in
human cells both are hallmarks of cancer. A number of multiprotein complexes are involved in all
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Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
DNA replication and DNA repair processes and have to precisely cooperate to avoid chromosomal
aberations. To analyze the formation and transport of these protein complexes in living cells is at
forefront of modern biomedical sciences. Fluorescence correlation spectroscopy is a proven technique
to measure mobility of fluorescent molecules in vivo by analyzing the temporal fluorescence
fluctuations arising from molecules diffusing through a very small femto-liter detection volume. The
small detection volume may be obtained by the use of confocal optics. Typical concentrations of
fluorescently tagged molecules in fluorescence correlation spectroscopy are in the nanomolar range,
corresponding to one or a few molecules simultaneously present in the observation volume.
Fluorescence correlation spectroscopy also allows to quantify the number of fluorescence molecules
and their concentration in human cells on a millisecond time scale as previously performed by the
Galway group.
To analyze replication and repair proteins human cells will be transfected with plasmids to express
these proteins fused to green or red fluorescent proteins. Co-expressing green and red fluorescent
proteins fused to different replication and repair proteins allows to determine the complex formation
of these proteins in a quantitative manner using fluorescence cross-correlation spectroscopy. To
analyze these protein complexes in vivo the cells will be synchronized in the cell cycle or treated with
DNA damaging agents following procedures established in the Galway group. Then the mobility and
the complex formation of the DNA replication and repair proteins fused to autofluorescent proteins
will be determined in cells progressing through the cell cycle and after DNA damage using
fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy, which are
both established in the Galway group. These studies will allow the quantitative analysis of cell cycle
and DNA repair processes monitoring the assembly and disassembly of key protein complexes in a
single cell and a single nucleus with a high time resolution, which cannot be performed with any
other technique. These studies will give new insights into the complex organization of DNA
replication and DNA repair of human cells with a high resolution of time and space.
Unique selling points of PhD project in NUI Galway:
The student will gain experience in multiple areas of cell cycle control and advanced microscopy
learning state-of-the-art biophysical, biochemical and cell biological techniques including
fluorescence correlation spectroscopy, fluorescence cross-correlation spectroscopy, fluorescence
recovery after photobleaching, and fluorescence-lifetime imaging microscopy.
The project supervisor is a member of the Centre for Chromosome Biology (CCB) at NUI Galway in
Ireland and has years-long experience in advanced microscopy. The project supervisor closely
cooperates with research groups at NUI Galway and with international laboratories to advance the
knowledge in the mechanisms of genome instability. CCB comprises a highly interactive network of
researchers who are interested in topics focusing the biology of genomes.
http://www.chromosome.ie/
The Centre currently consist of 11 groups with more than 90 researchers and support staff. Their
interests are focused on all molecular aspects underlying chromosome replication, segregation,
repair, evolution, chromatin regulation and transcription. To investigate chromosome biology
processes involved the Centre has available a range of technologies available at the molecular,
cellular and organismal level.
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Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
Name & contact details for project queries, if different from PI named above:
as above
Please indicate the graduates of which disciplines that should apply:
Graduates with a background molecular gentics/biology, biochemistry, cell biology, biophysics or
related disciplines should apply.
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):
Y