PhD Research Studentship The influence of baculovirus gene deletions on recombinant protein production

an industrial studentship with Oxford Expression Technologies Ltd

Supervisors: Prof Linda King (Oxford Brookes), Prof Robert Possee (NERC) and Dr Richard Hitchman (OET Ltd)

Eligibility:
Applicants should have a good Honours degree (2.1 or equivalent) and either have been educated to degree level through the medium of English or have TOEFL 600 (250) / IELTS 7 or equivalent

Starting in October 2007

Value p.a. £11,500 bursary, & fees

Closing Date: 21st May 2007
Interviews will be held on either June 6th, 7th or 8th

Project Description
Baculoviruses have long been used as vectors to produce recombinant proteins in insect cells and recently Oxford Expression Technologies have developed a novel system that enables multiple recombinant viruses to be produced in high throughput, robotic systems. However, the expression system still relies upon virus infection of insect cells are the requirement for protein
production in an infected and dying cell. Studies have shown that deleting some non-essential virus genes can have positive effects on protein production, for example, deletion of the chitinase gene enhances the production of secreted and membrane-targeted proteins. Deletion of cathepsin, a cysteine protease, enhances the quality and quantity of proteins susceptible to degradation by this class of protease. The purpose of this studentship will be to investigate the possibility that other virus gene deletions may have a positive, beneficial effect on recombinant protein production.

The sequence of the AcMNPV genome is known and indicates about 150 open reading frames of which it is predicted about 60% encode for genes essential for replication. The other 40% encode genes predicted to be non-essential for virus replication in cell culture and therefore are potential candidates for gene deletion. The Oxford labs have a well established mechanism for
creating gene deletions, using bacmid technology (where the virus genome is maintained as a replicon in bacterial cells). The MPhil phase of the project will be to identify candidate genes using bioinformatics, create a test virus expressing three reporter genes (expressing easily assayable cellular, membrane-targeted and secreted proteins) and systematically delete the candidate genes from this virus. It is envisaged that the PhD stage will involve testing gene expression using a variety of techniques – molecular, biochemical and cellular and choosing one or two candidate virus mutants for further detailed characterisation and possible exploitation through OET.

The student will benefit from a well established collaboration between the three Oxford partners, excellent facilities, an excellent PhD training programme offered by the School of Life Sciences and the chance to collaborate with a newly established University spin-out company.

An opportunity to develop teaching skills in higher education may be included in the training available with this studentship.

To discuss the project and for any other scientific queries contact Richard Hitchman. Email Dr Richard Hitchman

To apply for this project, applicants should quote the title of the studentship and include a letter of application, CV and the names and addresses of two academic referees (one of whom can also comment on the applicant’s potential for teaching)

Applications will only be accepted by post, and not by email, to:

Ms Angela Robinson
Research Administrator
School of Life Sciences
Oxford Brookes University
Headington
Oxford
OX3 0BP

Tel: +44 (0) 1865 483295

Email: Ms Angela Robinson