Post-doc position announcement

Nobody nobody at hgmp.mrc.ac.uk
Tue Apr 27 04:07:46 EST 2004


Please note, the application deadline for this position in Chris 
Hawes' lab at Oxford-Brookes University is fast approaching.  Get at 
least an informal application via email in by the 29th and it can be 
considered.



Salary: =A3 23737-=A325894



Closing date: 29th April 2004



A three-year postdoctoral research assistantship is now available to 
work as part of a large European Consortium working on the production 
of recombinant pharmaceuticals in plants.  The prime aim of the 
project is to build on previous proof of concept studies and to take 
at least one therapeutic monoclonal antibody through to clinical 
trials. Initially a range of target molecules directed at four 
diseases (HIV, tuberculosis, rabies and diabetes) will be worked on 
by the consortium.  The programme is divided in the six workpackages 
as follows:



1.	Indication areas and target molecules
2.	Risk assessment, biosafety and communication
3.	Plant production platforms
4.	Enabling technologies and expression strategies
5.	Scale-up, processing, regulatory affairs and quality control
6.	Clinical trials



The Oxford Group will be working on workpackage 4, which is 
specifically aimed at optimising the expression and production of 
proteins in nuclear transformed plants.  The majority of the work to 
be concentrated on optimising the performance of the secretory 
pathway. Specific objectives of the workpackage are:

1.	Thorough systematic analysis of subcellular localisation and 
stability of target proteins.
2.	Differential proteomic analysis of transgenic plants 
expressing the target proteins, to identify changes in the abundance 
of known and novel endogenous proteins involved in the synthesis, 
structural maturation and trafficking of the introduced targets. Key 
factors involved in response to heterologous protein expression will 
thus be identified. This will provide a toolkit that can be used to 
maximise accumulation of all targets.
3.	Generation of plants overexpressing known chaperones and 
folding catalysts, and intracellular trafficking and sorting 
determinants. These plants will be crossed with plants expressing the 
target molecules.
4.	Targeting of proteins with low intracellular stability to 
alternative sub-cellular compartments.
5.	Assessment of highly expressed proteins for their 
post-translational modifications, namely glycosylation and 
proteolytic maturation/degradation. If proteolytic 
maturation/degradation. appears to affect the yield of biologically 
active molecules we will devise approaches to overcome the problem 
(i.e., knocking out proteases and targeting to alternative 
subcellular locations).
6.	The modifying enzymes of the Golgi complex will be 
"humanized" by genetic engineering, to overcome possible problems of 
antigenicity and allergenicity of the recombinant pharmaceuticals due 
to plant-specific Golgi-mediated modifications of glycans.
7.	Construction of a plant virus-based system for inducible 
expression and high yield of the target proteins



The Brookes group will be responsible for much of the microscopy 
involved in the project and as such experience in both light and 
electron microscopy is essential. Initially the research assistant 
will be responsible for immunolocation studies at both fluorescence 
and EM levels of the target proteins in tobacco plants and in plants 
that have had key components of the secretory pathway, such as 
endoplasmic reticulum chaperones, modified to increase protein 
production levels. Fluorescent protein technology will also be used 
track the fate of expressed proteins in vivo and as such some 
experience in the production of GFP constructs will be an advantage. 
At Oxford we have produced a range of fluorescent protein constructs 
targeted to the various organelles of the secretory pathway and have 
a range of plants expressing these constructs.



The Oxford Brookes Plant Cell Biology group is particularly well 
equipped for both electron microscopy and confocal microscopy with 
all the associated preparative equipment such as a high-pressure 
freezing, freeze-substitution facility. The postdoc. will be working 
in a group currently comprising 4 postdoctoral research assistants, 
two PhD students and three technicians all mostly working on aspect 
of the higher plant secretory pathway.  As this is a collaborative 
programme there will be the opportunity to work closely with other 
groups both in the UK, especially at Warwick University and within 
Europe.



Application forms available from:



<http://www.brookes.ac.uk/vacancy/>http://www.brookes.ac.uk/vacancy/



or



Human Resources,

Wheatley Campus
Oxford
OX33 1HX, UK



=46urther details on the laboratory can be found at: 
<http://www.brookes.ac.uk/bms/gfp>http://www.brookes.ac.uk/bms/gfp 
and for any queries regarding the post contact Chris Hawes - 
<mailto:chawes at brookes.ac.uk>chawes at brookes.ac.uk



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C. John Runions, Ph.D.
School of Biological and Molecular Sciences
Oxford Brookes University
Oxford, UK
OX3 0BP

email: <mailto:jrunions at brookes.ac.uk>jrunions at brookes.ac.uk
phone: +44 (0) 1865 483 964

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