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PI name & contact details:
School:
Has project been agreed with head (or nominee) of proposed registration school?
Research Centre / group affiliation:
Research group / centre website:
Centre for Chromosome Biology / Genome Stability
Laboratory http://www.chromosome.ie
http://www.chromosome.ie/researchers/lowndes PI website / link to CV:
Brief summary of PI research / research group / centre activity:
If you are already involved in relevant scholarly activities relating to Brazil, please mention them here.
Professor Lowndes’ research career spans two decades in leading research laboratories in the USA,
UK and Ireland. He was appointed to the Chair of Biochemistry at the National University of Ireland
Galway in 2001 where he leads the Genome Stability Laboratory. His group investigates mechanisms of sensing and responding to DNA damage using yeast, DT40 and human cells. His leadership of the
Centre of Chromosome Biology ( www.chromosome.ie/ ) has been pivotal in positioning NUIG at the forefront of Irish cancer biology. In 2003, Professor Lowndes was elected to the membership of the
European Molecular Biology Organisation, one of 5 EMBO members in Ireland.
Title & brief description of PhD project (suitable for publication on web):
A conditional approach to probing ATR function during DNA synthesis :
The overarching aim of this project is to further our understanding of the role of the ATR kinase, a central regulator of the DNA damage response, in the control of DNA replication and maintenance of normal genome stability. Our study will elucidate the essential role of
ATR during normal cellular proliferation and upon replication stress and to identify potential new targets for cancer treatment.
Hypothesis and specific aims :
Our general hypothesis is that ATR maintains genome stability by facilitating both the recruitment and regulation of multiple proteins at sites of DNA synthesis. Our more specific hypotheses are:
1) During normal cell cycles ATR performs a specific role during late S phase
2) ATR functions in faithful transmission of epigenetic marks
3) Absence of ATR causes accumulating genomic damage leading to cell death
Experimental Plan: Using an already generated novel conditional null ATR cell line we will carry out:
1) Analysis of cell cycle progression using live cell microscopy and DNA combing
2) Combine a new methodology for purifying newly replicated DNA with SILAC-assisted quantitative proteomics to define the ATR-dependent proteome of newly replicated DNA
This work will illuminate the regulation and mechanism of action of the ATR kinase. Results obtained will be published in leading internationally peer review journals and new factors identified will be assessed for ther potential as new cancer therapeutic targets.
Unique selling points of PhD project in NUI Galway:
1) The PI is an internationally leading researcher in genome stability studies
2) Excellent multidisciplinary laboratory facilities (note, in July 2013 the host laboratory will relocate to the new BioScience Building at NUIG , see http://www.guf.ie/index.php/priority-

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projects/project_detail/biosciences-research-building1/ )
3) Strong collaborative links with international leaders in the field within Europe and the
USA.
4) Excellent track record in the field
5) Strong funding record, including national (SFI/HRB), international (EU) and philantrophic
(O’Sullivan Biomedical Trust) agencies
6) Strong strategic focus on Biomedical Science
7) Strong technical background in: a.
Genetics (use of gene targeting for either ablating gene function or acquisition of new functions) b.
Biochemistry (protein functions & interaction, quantitiative proteomics)
8) c.
Cell Biology (fixed and live cell microscopy) d.
Advanced specialist techniques (DNA combing, isolation of proteins on nascent
DNA, elutriation, stable isotope labelling with amino acids in cell culture or SILAC)
Nearby Brazilian community (see: http://euscreen.eu/play.jsp?id=EUS_346071ABF1C64166BF02025C40B29ED8 )
Please indicate the graduates of which disciplines that should apply:
Biochemistry, Biotechnology, Biomedical Science, Cell Biology, Genetics, Pharmacology,
Physiology, or any other comparable discipline of Molecular Biology
Ciência sem Fronteiras / Science Without Borders Priority Area:
Please indicate the specific programme priority area under which the proposed PhD project fits- only one :
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
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
X
New technologies in constructive engineering
Please indicate which of the following applies to this project (referring to Science Without Borders):
Suitable only as a Full PhD (Y/N): _
_
Available to candidates seeking a Sandwich PhD arrangement (Y/N): _
_