Download Nociceptin mediated microvascular inflammation during sepsis

The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Neuroscience
ROLE OF MITOCHONDRIA IN C9ORF72-RELATED ALS/MND
Supervisor: Kurt De Vos, Andy Grierson
Project:
Expansions of a noncoding GGGGCC hexanucleotide repeat in the C9ORF72 gene
are the most common genetic defect found to date in ALS and frontotemporal
dementia (FTD). How these expansions cause disease is not known, but may involve
both loss-of-function (C9ORF72 haploinsufficiency), and gain-of-function (repeatassociated non-ATG (RAN) translation, RNA toxicity) mechanisms.
Mitochondria play a central role in the pathogenesis of familial and sporadic
amyotrophic lateral sclerosis (ALS) / motor neuron disease (MND). Mitochondria are
the main source of oxidative stress; mitochondria determine excitotoxicity because
they are the key calcium-buffering organelles in motor neurons; mitochondria
regulate protein homeostasis, and mitochondrial dysfunction causes ER stress; last
but not least mitochondria produce most energy (ATP) required to maintain
neuronal function and diminished ATP synthesis and mislocalisation of mitochondria
kills neurons.
In this project you will quantify mitochondrial function in loss- and gain-of-function
models
of
C9ORF72-related
ALS
as
well
as
in
patient-derived
cells
to
comprehensively test the role of mitochondria in C9ORF72-related ALS and to
identify novel therapeutic avenues.
This project is funded by an MNDA Prize Studentship (www.mndassociation.org).
The studentship provides full support for tuition fees (at UK/EU levels) and a tax-free
annual stipend (£16,000-£17,000). Start date is October 2014.
Entry Requirements:
Candidates must have a first or upper second class honors degree or significant
research experience.
Enquiries:
Interested
candidates
should
in
the
first
instance
contact
Kurt
De
Vos
([email protected]).
How to apply:
Please complete a University Postgraduate Research Application form and attach at
least two references to your application. To complete the application form please
visit: www.shef.ac.uk/postgraduate/research/apply.
Please clearly state the prospective main supervisor in the respective box and select
‘Neuroscience’ as the department.
Website: http://www.shef.ac.uk/neuroscience
Closing date: 3rd February 2014