Please find below details of a PhD. studentship which is available in
my group with a start date of September 2006.
I would be delighted if people could pass this on to any prospective
candidates, and pin it up on relevant notice boards.
Many thanks
Perdita
EPSRC/RSC Funded PhD. Studentship at the School of Chemistry,
University of Edinburgh in the group of Dr. Perdita Barran
Start Date September 2006
‘To Develop and Evaluate Ion Mobility as a Proteomic Tool’
The goal of this studentship is to evaluate Ion Mobility Mass
Spectrometry as a proteomic device; both to augment ‘standard’ MS based
analyses of digested proteins, and also to provide detailed information
on the intrinsic interactions which govern the structure(s) of
proteins. The candidate will posses or be about to obtain a degree in
Chemistry, Chemical Physics, Physics or Biochemistry. They will join an
extremely active research group; further details can be found here:
http://homepages.ed.ac.uk/pbarran/PBRG/. Research will be conducted in
an interdisciplinary environment which will involve extensive
collaboration with other research groups. In the course of this PhD
project, the candidate will be trained in biological mass spectrometry
and LC based techniques, protein handling, Molecular Dynamics, and have
access to an extensive range of Biophysical instrumentation and
methodologies.
The studentship is available to all who fulfil the standard eligibility
requirements of the UK research councils.
We have recently implemented the technique of gas-phase Ion Mobility
[1,2] on a Quadrapole Time of Flight Mass Spectrometer with the
principle aim of studying the structures of biologically relevant
molecules. [3, 4]. One of the most exciting challenges of this new
technology is its use as a secondary separation device after HPLC
analysis and prior to mass separation. Use of the instrumentation in
this fashion gives rise to 3 dimensional data sets which comprise LC
elution times, drift times and mass spectra. We will employ digested
proteins obtained from C. elegans and compare results to those obtained
via LC-MS/MS.
This project will also examine the structures of a family of
antimicrobial peptides known as b-Defensins. These cationic,
amphipathic peptides, 30-45 amino acids in length, with exceptionally
low sequence homology, save for 5 or 6 cysteines. Their activity is
presumed related to a disulphide bridging pattern, which in turn
contributes to a common b-sheet motif. We have examined several novel
b-defensins using mass spectrometry, and in preliminary investigations
focused on a recently discovered defensin which contains only 5
cysteine residues (defr1) [5]. Defr1 was found to be a covalently bound
dimer, due to an inter-molecular disulphide bond between the ‘spare’
cysteine on each monomer residue. Peptide mass mapping revealed several
different internal disulphide connectivity’s, and indeed it elutes
under a weak LC gradient as a very broad peak, due to a mixture of
differently connected isoforms. Using our LC-IMS-MS device we will be
able to examine the mobility’s of the defr1 isomers and other
rationally designed defensins, and assess their different
conformations. Other defensins for example the 6 cysteine defr1
analogue, have been shown to form dimers by mass spectrometry [5] and
the mode of action of defensin’s is linked to their aggregation
tendency. In this project Ion Mobility will allow us to interrogate
structural changes in these and higher order aggregates and this
‘bottom up’ approach will provide insights into the structure-activity
relationships of this important class of proteins.
For further details contact Dr. Perdita Barran [log in to unmask]
To apply please fill in an application form available here:
http://www.chem.ed.ac.uk/postgrad/postgrad_contact.html
1.Wyttenbach, T.; Bowers, M. T., Gas-phase conformations: The ion
mobility/ion chromatography method. In Modern Mass Spectrometry, Topics
In Current Chemistry, 2003; Vol. 225, pp 207-232.
2.Creaser C.S., G. J. R., Bramwell C.J., Noreen S., Hill C.A., Thomas
C.L.P., Analyst 2004, 129, (11), 984 -994.
3.Barran, P. E.; Polfer, N. C.; Campopiano, D. J.; Clarke, D. J.;
Langridge-Smith, P. R. R.; Langley, R. J.; Govan, J. R. W.; Maxwell,
A.; Dorin, J. R.; Millar, R. P.; Bowers, M. T., Is it biologically
relevant to measure the structures of small peptides in the gas-phase?
International Journal Of Mass Spectrometry 2005, 240, (3), 273-284.
4.Barran, P. E.; Roeseke, R. W.; Pawson, A. J.; Sellar, R.; Bowers, M.
T.; Morgan, K.; Lu, Z. L.; Tsuda, M.; Kusakabe, T.; Millar, R. P.,
Evolution of constrained gonadotropin-releasing hormone ligand
conformation and receptor selectivity. Journal Of Biological Chemistry
2005, 280, (46), 38569-38575.
5.Campopiano, D. J.; Clarke, D. J.; Polfer, N. C.; Barran, P. E.;
Langley, R. J.; Govan, J. R. W.; Maxwell, A.; Dorin, J. R.,
Structure-activity relationships in defensin dimers - A novel link
between beta-defensin tertiary structure and antimicrobial activity.
Journal Of Biological Chemistry 2004, 279, (47), 48671-48679.
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=============================================
Dr. Perdita Barran
EPSRC Advanced Research Fellow
The School of Chemistry
The University of Edinburgh
Joseph Black Building
King's Buildings
Edinburgh EH9 3JJ
UK
t: +44 (0) 131 650 7533 (office)
t: +44 (0) 131 651 3037 (lab/SIRCAMS)
f: +44 (0) 131 650 7533
w: www.chem.ed.ac.uk/staff/barran.html
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