Generation of DNA sequence-specific anti-cancer drugs through closed loop evolution of aptamers

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Project description

PLEASE NOTE THIS IS A PROJECT FROM THE SCHOOL OF MEDICINE; APPLICATIONS NEED TO BE DIRECTED THERE.

The objective of this PhD project is to produce drugs carrying only the `on-target' effect of cytotoxic anti-cancer compounds.

The study aims at improving tools for bioprocessing to develop a closed loop algorithm modeling procedure to generate highest specificity binding between (DNA) aptamers and anti-cancer `drugs' that bind directly to DNA. The University of Manchester has developed a lead in the use of micro-arrays of aptamers for high throughput screening and rapid analysis of drug-aptamer partners with appropriate levels of specificity.

The procedure offers the potential for low cost and rapid development of new therapeutics whose binding selectivity is determined through the modeling of real-world binding specificity of heteroduplexes formed between drug-DNA associations. Short oligonucleotides are readily scaled-up and in high yield.

Intrinsically, aptameric micro-arrays provide insight into how a range of biological structures influence binding specificity. Sequences for aptamers are to be derived from human cancer cells and normal cells. Cisplatin and analogues will be tested for binding these aptamers. From models generated through these binding studies, novel analogues of cisplatin will be generated to possess specific DNA sequence (aptamer) binding where the DNA sequence is uniquely located or amplified in cancer cells; Ph+ cell lines and neuroblastoma cell lines will be tested respectively.

The main study will be based at the Manchester Interdisciplinary Biocentre and will access the only Combimatrix B3 DNA synthesizer in the UK. Extensive training in DNA synthesis and microarray techniques will be provided. Upon completion of the project, the candidate will be ideally placed to progress into a wide variety of post-doctoral research positions both in academia and industry.Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in bioinformatics, biochemistry or analytical chemistry. A Masters degree in a similar area as well as previous experience of computer programming and data analysis would be an advantage.

This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to provide evidence of their ability to provide self-arranged funding. Annual tuition fees for this project are currently:

UK/EU nationals: 6, 300 Pounds
Non-EU nationals: 17, 000 Pounds

Please direct applications in the following format to the project lead, Dr Philip Day (philip.j.day@manchester.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 your research experience to date
* Evidence of funding.

Any enquiries relating to the project and/or suitability should be directed to Dr Day at the address above.

Http://www.medicine.manchester.ac.uk/staff/90330

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