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Three year PhD Studentship in MRC Human Genetics Unit, Edinburgh

Three year PhD Studentship in MRC Human Genetics Unit, Edinburgh - Drosophila Forum

Three year PhD Studentship in MRC Human Genetics Unit, Edinburgh - Drosophila melanogaster Forum. Discuss and post questions about FlyBase, Drosophila cloning, fruit fly gene crosses expression and analysis.


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Old 08-13-2008, 01:07 PM
Liam Keegan
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Default Three year PhD Studentship in MRC Human Genetics Unit, Edinburgh




Dept/School Human Genetics Unit, Medical Research Council
Project Title Drosophila Screen for Regulators of RNA editing
Project Supervisor(s) Dr L Keegan, Dr M O’Connell
Application Deadline 22 August 2008

The MRC Human Genetics Unit is offering a three year PhD studentship
funded by the Scottish Motor Neurone Disease Association working under
the supervision of Dr Liam Keegan. This excellent opportunity would suit
a student finishing an MSc project on Drosophila or a student graduating
with a good training in Genetics and Developmental Biology and some
experience of working with Drosophila or another efficient model organism.

The project is based in lab studying RNA editing. This is a step in RNA
processing that affects the expression levels and the amino acid
sequences of vertebrate glutamate receptors. Loss of RNA editing has
been reported in motor neurones of ALS patients (Kawahara (2004) Nature
427, 801). and following ischaemia in central neurons (Peng (2006)
Neuron 49, 719). Glutamate is the major excitatory neurotransmitter in
vertebrate CNS and loss of the edited forms of vertebrate glutamate
receptors is expected to promote neuron death by allowing excessive
calcium influx.

Vertebrates have multiple genes encoding the relevant RNA editing
enzymes, called ADARs, whereas the fruit fly Drosophila has a single
Adar gene. The project will take advantage of Drosophila to carry out a
genetic screen for proteins that interact with and regulate the activity
of these RNA editing enzymes. As in vertebrates flies mutant for the
Adar gene lose RNA editing in a range of target transcripts encoding ion
channel subunits. The flies have locomotion defects from birth, reduced
viability and show age-dependent neurodegeneration. All phenotypes are
rescued by expression of either Drosophila or human ADARs.

Adenosine to inosine RNA editing targets stretches of double stranded
RNA which may be either short hairpins within pre-mRNAs or long
stretches of dsRNA formed by transposable elements or by antisense
pairing of complementary transcripts. Site-specific editing within
pre-mRNAs affects RNA splicing and recodes open reading frames to
produce ion channel variants. Non-specific editing within long dsRNAs
antagonizes the RNA interference that is triggered by these dsRNAs. The
screen will potentially contribute to understanding both these roles of
ADARs.

The screen will identify regulators of ADAR activity in the fly by
looking for modifiers of viability in Adar loss of function mutants that
have reduced viability already or by looking for suppressors of
lethality caused by early overexpression of ADAR (Keegan (2005) Embo J
24, 2183). The screen uses a standard, efficient method in Drosophila
that begins with looking for effects of larger heterozygous deficiencies
and then refining the effects down to specific genes. The objective is
to identify regulators that are conserved and likely to be informative
about the regulation of editing in vertebrate neurons and to focus on
the roles of these in regulation of ADAR activity and in neuroprotection.

Kawahara (2004) Nature 427, 801
Peng (2006) Neuron 49, 719
Keegan (2005) Embo J 24, 2183

Lab information is available at:
[Only registered users see links. ]
[Only registered users see links. ]

Funding Notes
This 3 year PhD studentship will be funded by the Scottish Motor Neurone
Disease Association and we ask potential applicants to note that while
there are eligibility criteria for this studentship, we encourage all
qualified EU students to apply.
Further information regarding eligibility can be found on
[Only registered users see links. ]
The studentship offers an attractive stipend and a comprehensive
transferable skills training programme.

Applicants should submit a covering letter explaining why you are
interested in applying. Applications should include a full up-to-date
C.V. (include vacation address), and names and addresses of two academic
referees, sent by 22 August 2008 to: [Only registered users see links. ] or
Studentships, MRC Human Genetics Unit, Western General Hospital, Crewe
Road, Edinburgh EH4 2XU.

--
Dr. Liam Keegan Tel No. ++ 44 (0)131 467 8417

MRC Human Genetics Unit Fax No. ++ 44 (0)131 467 4856

Western General Hospital
Crewe Road

Edinburgh EH4 2XU

UK

[Only registered users see links. ]

[Only registered users see links. ]

[Only registered users see links. ]


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