BBSRC Industrial CASE PhD Studentship 2013
PhD in Biochemistry
The University of Manchester -School of Pharmacy & Pharmaceutical Sciences
Complete 3D description of dynamic behaviour of enzyme mimics to support predictive, systems-driven medicine
Medicinal Chemistry
Dr Elena Bichenkova
This fully-funded studentship investigates the fundamental mechanisms underlying the action of chemical ribonucleases. The eventual aim is to provide improved understanding of vital biological mechanisms and facilitate predictive, systems-approaches in bioscience, applicable at the level of both individual molecules and complex bio-systems.
The project incorporates a training placement at Conformetrix Ltd, a leading company in optimising drug discovery and design to help the pharmaceutical sector generate more efficient and safer medicinal products.
Chemical ribonucleases are 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. 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.
The PhD will seek to resolve these issues by using unique proprietary NMR technology recently invented by Conformetrix, 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 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 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 biology, biophysics, computer modelling and bioinformatics. The opportunity for placement at Conformetrix provides access to their unique technology, and offers 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 or a related area. Previous experience in peptide and oligonucleotide synthesis, organic chemistry, analytical and spectroscopic techniques and computational chemistry would be an advantage.
Please direct applications in the following format to Dr Elena Bichenkova (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 Monday 6 May 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
