Postdoctoral Research Assistant in Gene Therapy

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Oxford_Logo_Square_Blue.jpgPostdoctoral Research Assistant in Gene Therapy Nuffield Division of Clinical Laboratory Sciences, RDM, John Radcliffe Hospital, Oxford

Grade 7: Salary in the range £31,076 - £32,958 p.a.

We are seeking an enthusiastic Postdoctoral Research Assistant in gene therapy to work with the Gene Medicine Research Group, directed by Associate Professors Deborah Gill and Steve Hyde.

The successful applicant will be keen to participate in translational research and have responsibility for investigating lentiviral gene delivery to the airways for expression of monoclonal antibodies, particularly broadly neutralising antibodies to protect against influenza. The project will involve the design and production of lentiviral vectors, and delivery to a range of animal models of influenza challenge.

You will hold, or be nearing completion, of a PhD (DPhil) in gene therapy, or a closely related field. Relevant laboratory experience in recombinant virus and mammalian cell culture, lentiviral production and molecular cloning is essential. Specialist knowledge in monoclonal antibodies, influenza or other respiratory infections would be desirable. A Home Office Licence with experience in gene delivery in vivo would be an advantage. The position is full-time, fixed-term for 36 months and funded by the Wellcome Trust.

Candidates are encouraged to discuss their needs and preferences for work arrangements at interview.

For further details, including a job description and person specification, please see below. Applications are particularly welcome from women and black and ethnic minority candidates, who are under-represented in research posts in Oxford.

The closing date for applications is 12.00 noon on 14 June 2017.

Overview of the role

Background:

Influenza A is a major worldwide health risk causing >500,000 deaths each year. Neither prior infections, nor current vaccinations, provide lasting protection from seasonal epidemics. The seasonal vaccine must be continually reformulated in an attempt to keep pace with the viral evolution and, in addition, suffers from reduced efficacy in the elderly and immunosuppressed, groups that constitute the majority of seasonal influenza deaths. Importantly, available vaccines also fail to provide protection when highly diverged viral strains emerge to initiate human pandemics. We have exploited the recent ability to clone monoclonal antibodies (mAbs) that neutralise widely diverse strains of influenza from single human B cells to use passive immunity to protect against a wide range of strains of influenza.

Our Aim:

We plan is to utilize our lentiviral platform to provide long-lasting passive immunity. Using recombinant lentiviral vector, which is pseudotyped for efficient targeting of the airways (rSIV.F/HN), we aim to express mAbs from the lung. In collaboration with Professor Alain Townsend (University of Oxford), who provides access to novel human mAbs targeting influenza, we will use animal models of influenza challenge to demonstrate protection against infection. We anticipate that rSIV.F/HN vector- dependent long-term passive immunity could be valuable in two settings: (i) acute treatment of high-risk, immune-compromised individuals suffering from seasonal flu; and (ii) rapid and widespread protection of high-risk essential personnel (such as first responders and other health care workers) during forecast pandemics of highly pathogenic flu. The Position: Applicants are invited for a Postdoctoral Research Assistant position at the Oxford University Radcliffe Department of Medicine (NDCLS) to participate in this new collaborative project. The position is available for 36 months.

Key Tasks:

The successful applicant will lead: (a) Design and testing of lentiviral vector genomes incorporating multiple vector configurations to express candidate mAb sequences; (b) Production and testing of high purity lentiviral vectors; (c) Evaluation of mAb expression in animal models of influenza challenge; (d) Assessment and selection of lead candidate for future translation.

Responsibilities:

  • To participate in the Gene Medicine Research Group programme to investigate the use of lentiviral gene delivery to the lung for disease treatment.
  • To specifically focus on meeting the research project objectives to assess the expression of monoclonal antibodies against influenza in the lung.
  • To perform research, using techniques required for vector design and construction, including, large-scale vector expression and testing in animal models.
  • To investigate and establish new methodologies for evaluation of immunity to influenza challenge.
  • To assist laboratory supervision and training of new students and junior research assistants in lab methods.
  • To analyse and report the results of work undertaken to the team and collaborators.
  • To perform any comparable duties that may be required for the smooth running of the laboratory including being responsible, with others, for the biological safety of the laboratory.

Communication:

  • To communicate with Profs Deborah Gill and Steve Hyde and other members of the group as required, to ensure they are kept fully up to date with scientific progress.
  • To help prepare data for scientific papers and reports and verbal presentations at meeting and conferences. To maintain confidentiality regarding research data.

 


Friday, May 19th 2017

 

Light microscope image of a human airway liquid interface cultures. Dark patches are mucous.

 

Large scale lentivirus production in suspension culture.

 

Human airway liquid interface cultures transduced with a lentivirus expressing Luciferase.

 

A CFTR Western blot, to confirm protein production in cell culture.

 

A pellet of E.coli containing a plasmid expressing a pink fluorescent protein.

 

A frozen vial of GL67A (left) and a frozen vial of pGM169 plasmid DNA (right)

 

E.coli from a large scale industrial production of our clinical trial plasmid pGM169.

 

Pellets of DNA following precipitation.