Complete 3D description of dynamic behaviour of enzyme mimics: role of various structural elements in catalysis and interactions with bio-target

Dr Elena Bichenkova

This project will investigate the fundamental mechanisms underlying the action of chemical ribonucleases, a particular class of enzyme mimics that can be fabricated by chemical fusion of two inactive precursors. This produces a novel, biologically active chimeric molecule capable of recognising and cleaving physiologically significant RNA.

These biocatalytic hybrids imitating recognition and catalytic domains of natural enzymes might be useful as models to investigate fundamental principles of biomolecular catalysis. This should provide improved understanding of vital biological mechanisms and facilitate predictive, integrative and systems approaches in bioscience, applicable at the level of both individual molecules and complex bio-systems.

Little is known about biological rules behind the catalytic activity of these artificial enzymes. Traditional spectroscopic approaches have proven unsuccessful in providing solutions due to their incompatibility with the high structural flexibility of these biomimetics and repetitive nature of their building blocks, which greatly complicates decoding experimental information.

This collaborative project aims to resolve these issues by using unique proprietary NMR technology recently invented by our industrial partner, Conformetrix Ltd, and deliberately designed to explore the dynamic 3D-shape of such highly flexible molecules. A synergetic combination of isotopic labelling of selected artificial enzymes with this advanced technology will allow us to investigate their structural and dynamic properties and thus identify the role of different structural elements in bio-catalysis. By providing a complete 3D description of the dynamic behaviour of these enzyme mimics, we hope to overcome the limitations of traditional spectroscopic techniques and reveal biological mechanisms underlying their recognition and catalytic capabilities.

Training will be carried out at the interface of chemistry, biochemistry, structural and chemical biology, biophysics, computer modelling and bioinformatics. The opportunity for placement at Conformetrix will provide access to their unique technology, and offer expert insight in commercial aspects such as marketing, IP and licensing.

This 4-year full-time studentship provides full support for tuition fees, annual minimum tax-free stipend of £13,726 and a conference/travel allowance. The project is due to commence October 2013 and is open to UK/EU* nationals only due to the nature of the funding.

The PhD will provide an ideal platform to progress onto a future career within academic or industrial settings involving pharmaceutical sciences, medicinal chemistry, nanoscience or biotechnology.

Applicants should hold a minimum upper-second honours degree (or equivalent) in chemistry with previous experience in peptide and oligonucleotide synthesis, organic chemistry, analytical and spectroscopic techniques. They must also be capable of working at the interface between chemistry, biology and nanotechnology. Experience in computational chemistry would be highly beneficial.

Please direct applications in the following format to Dr Elena Bichenkova (elena.bichenkova@manchester.ac.uk), via the apply button below:                   

• 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 your research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Bichenkova. Applications are invited up to and including Friday 12 April 2013.

*Applicants must be UK/EU nationals who have resided in the UK since at least 1 September 2010 in order to qualify for full funding.

http://www.pharmacy.manchester.ac.uk/staff/ElenaBichenkova

http://www.pharmacy.manchester.ac.uk/

http://www.conformetrix.com/

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