Dr Elaine Bignell

In this fully-funded 4-year BBSRC ICASE project, we will use genetically engineered microbes to synthesise designer drugs active against fungal diseases of man and poultry.

We will use genetically engineered yeast cells to synthesise biologically useful molecules called peptide aptamers (PAs). PAs are designer proteins composed of short amino acid chains, encased within a protein scaffold. A unique property of PAs is their ability to fold into highly diverse 3D structures which are capable of binding very specifically to other proteins.

The construction of libraries of randomised aptamer sequences creates a source of molecules having a plethora of unique conformations, and able to recognise individual combinations of charge, shape and hydrophobicity. In an era of antibiotic resistance access to such a diverse array of molecular structures provides an invaluable source of new drugs. The challenge with PAs has been efficient delivery into fungal cells, but by using nanoparticle-based drug delivery, developed at Blueberry Therapeutics, we can overcome this limitation.

PAs have several advantages over chemically-based medicines. As they bind very specifically to other proteins, PAs are likely to cause fewer side-effects than standard pharmaceuticals. The metabolism of peptide aptamers also yields naturally occurring amino acids, thereby limiting toxic side-effects. These attributes are highly appealing from a therapeutic viewpoint and our intention to mine them represents a new way of working on drug discovery.

The study will be conducted with the Manchester Fungal Infection Group (MFIG) and Blueberry Therapeutics. MFIG forms one of the foremost global centres for fungal diseases research and hosts a significant number of early career researchers. A placement at Blueberry will be incorporated to provide research experience in a commercial environment.

Extensive training will be provided in genetic engineering of model and pathogenic fungi, molecular fluorescence imaging in living fungal cells, high throughput screening for protein-interactions and generation of nanoparticle formulations of antifungal drugs. Such skills-sets will equip the successful candidate to progress into a postdoctoral career in a variety of clinical and biomedical areas.

The 4-year full-time BBSRC ICASE studentship provides full support for UK/EU tuition fees and an annual minimum tax-free stipend at RCUK rates (currently £13, 863). The project is due to commence October 2015 and is open to UK/EU* nationals only due to the nature of the funding.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in a biological/medical science or related area. A Masters degree in a similar discipline would be beneficial as would previous experience of some of the techniques referenced above.

Please direct applications in the following format to Dr Elaine Bignell (elaine.bignell<στο>imanchester.ac.uk):            

•       Academic CV

•       Official academic transcripts

•       Contact details for two suitable referees

•       A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Bignell.

*Applicants must be UK/EU nationals who have resided in the UK since at least 1 September 2012 in order to qualify for full funding.

http://www.inflammation-repair.manchester.ac.uk/mfig/

http://www.inflammation-repair.manchester.ac.uk/staff/ElaineBignell

http://www.blueberrytherapeutics.com/

http://www.mhs.manchester.ac.uk/postgraduate/