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. Karl McCullagh PhD,
[SWB] Karl.mccullagh@nuigalway.ie
Prof. Afshin Samali
[SWB] afshin.samali@nuigalway.ie
School:
School of Medicine and School of Natural Sciences
Has project been agreed with head (or
nominee) of proposed registration
school?
Research Centre / group
affiliation:
Dr Karl McCullagh’s Research group at the Regenerative
Medicine Institute (REMEDI) and Prof. Afshin Samali’s group in
Department of Biochemistry, both at the National University of
Ireland Galway.
Research group / centre website: http://www.remedi.ie/
http://www.apoptosis.ie
PI website / link to CV:
http://www.remedi.ie/people/dr-karl-mccullagh
http://www.nuigalway.ie/biochemistry/staff/samali/index.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.
Dr Karl McCullagh is an associated principal investigator at the Regenerative Medicine Institute
(REMEDI), NUI Galway. REMEDI is a relatively young state of the art biomedical research centre
established in 2004. The PI has extensive international experience working in North America, Italy
and UK, on signaling mechanisms regulating muscle adaptation to exercise/stress/injury. His
research group is now exploiting this to develop therapeutic interventions for neuromuscular
disease including muscular dystrophy.
Prof. Afshin Samali has extensive internationally recognized research experience in endoplasmic
reticulum stress. He is also Director of the Apoptosis Research Centre at NUI Galway and has
industrial links with; Ezose Sci Inc (USA), Connexios (India) and MannKind Corp. (USA) – all in the
area of ER stress.
Title & brief description of PhD project (suitable for publication on web):
Title: Targeting Endo/Sarcoplasmic Reticulum Stress as a novel therapy for muscle disorders.
Duchenne Muscular dystrophy (DMD) is the most common muscular dystrophy due to loss of the
sarcolemma localised protein dystrophin. Dystrophin is linked to several proteins including neuronal
nitric oxide synthase (nNOS), which is involved in intracellular signalling. In DMD and other muscular
dystrophies, nNOS is dislocated from the sarcolemma and is thought to contribute to the dystrophic
pathology. Recently, it was shown that increased cytoplasmic nNOS in muscles of mdx mice, a preclinical animal model of DMD, results in leakage of calcium from the endo/sarcoplasmic reticulum
Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
(ER/SR) due to nitrosylation of the SR ryanodine receptors. Whether dystrophic muscle is subject to
significant ER/SR stress and activation of the associated unfolded protein response (UPR) has not
been examined in great detail. Since ER stress is a novel therapeutic target for other diseases, we
intend to examine its therapeutic relevance in combating DMD. To this end, we have identified upregulation of ER stress genes in muscles of the mdx mice. We intend to characterize further the ER
stress / UPR activated pathways in muscles of mdx mice using standard gene expression analysis
and gene delivery of an ER stress activated reporter to muscles. An established ER stress/UPR
signature of gene activation will be examined at mRNA and protein levels in muscles across time
points covering the disease progression. Based on these findings pharmacological inhibition of
specific parts of the UPR pathway will be examined in the mdx mouse. Small molecule inhibitors
against UPR will be delivered chronically to the mdx mice before and after disease on-set followed
by muscle strength and cellular assessment of treated mice. This will be the first detailed
examination of ER stress in a pre-clinical animal model of DMD, and its potential as a novel
therapeutic target for treatment of muscle disorders.
Unique selling points of PhD project in NUI Galway:
NUI Galway projects should emphasise features that are not typically available in Brazil – specific equipment,
multi-disciplinarity, aspects of structured programme, links with industry, placements, links with other research
groups etc.
The project entails multidisplinary activities including cell culture, cell biology, viral and non-viral
gene transfer and working with genetic mouse models of disease. The infrastructure and support
staff can be found in the research centres involved;
http://www.remedi.ie/
http://ncbes.eurhost.net/
http://www.apoptosis.ie
Name & contact details for project queries, if different from PI named above:
Please indicate the graduates of which disciplines that should apply:
Graduates with a biological education preferably in one of the following; molecular biology,
biochemistry, physiology, biomedical sciences, biotechnology, or medicine.
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)
Health and Biomedical Sciences
Information and Communication Technologies (ICTs)
Aerospace
Pharmaceuticals
Oil, Gas and Coal
Renewable Energy
Universidade Nacional da Irlanda em Galway -- Ciência sem Fronteiras
Minerals
Biotechnology
Nanotechnology and New Materials
Technology of prevention and remediation of natural disasters
Biodiversity and Bioprospection
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____
Available to candidates seeking a Sandwich PhD arrangement (Y/N): __N___
Suitable for either/Don’t know: _Don’t know____