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Luminescent Molecular Probes to Facilitate Drug Discovery

  • Full or part time
  • Application Deadline
    Friday, February 14, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

Application details:
Reference number: SJB/CM/2020
Start date of studentship: 1 October 2020
Closing date of advert: 14 February 2020
Interview date: 1 March 2020

Primary supervisor: Dr Stephen Butler
Many drugs act by inhibiting enzyme activity. To increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical companies have robust assays to measure enzyme activity accurately. The aim of this project is to develop molecular probes that bind reversibly to specific biological anions (e.g. ADP), which are produced during pharmaceutically important enzyme reactions. Upon binding the anion, the probe will provide a luminescent signal that enables precise measurement of enzyme activity in real-time. This will provide a vital step towards the accurate determination of enzyme kinetics, enabling better selection and validation of drug candidates at an early stage in drug discovery, reducing effort pursuing compounds destined to fail at the more lengthy and costly phases of drug development. The student will gain excellent training in organic synthesis, study of host-guest interactions, bioassay development and cellular imaging.
Loughborough University is a top-ten rated university in England for research intensity (REF2014). In choosing Loughborough for your research, you’ll work alongside academics who are leaders in their field. You will benefit from comprehensive support from our Doctoral College, including tailored careers advice, to help you succeed in your research and future career.
Loughborough University has a flexible working and maternity/parental leave policy (https://www.lboro.ac.uk/services/hr/leave-absence/family-leave/) and is a Stonewall Diversity Champion providing a supportive and inclusive environment for the LGBT+ community. The University is also a member of the Race Equality Charter, which aims to improve the representation, progression and success of minority ethnic staff and students. The School of Science is a recipient of the Athena SWAN bronze award for gender equality.
Find out more: http://www.lboro.ac.uk/study/postgraduate/supporting-you/research/

Full Project Detail:
Enzymes that utilise polyphosphate anions (e.g. ATP) represent major targets in cancer drug discovery. Many drugs act by inhibiting enzyme activity, therefore, to increase confidence in the selection of lead drug compounds it is crucial that pharmaceutical companies have robust assays to measure enzyme activity accurately. Current assays require expensive and unstable antibodies, which prevent real-time analysis of enzyme activity.
This project will develop molecular probes that bind to specific polyphosphate anions (e.g. ADP), which are produced during pharmaceutically important enzyme reactions. Upon binding the anion, the probe will provide a luminescent signal that precisely measures enzyme activity in real-time. This will provide a vital step towards the accurate determination of enzyme kinetics, enabling better selection of drug candidates at an early stage in drug discovery, reducing effort in pursuing compounds destined to fail at more costly development phases. The student will have the possibility to spend time working in the laboratories of collaborators (UK, France), to test the probes in biological assays.
This project spans the areas of synthetic organic, supramolecular and biological chemistry. The student will gain excellent training in organic synthesis, study of host-guest interactions, bioassay development and cellular imaging. They will be supported by postdoctoral researchers within the Butler Group, and will be very well trained for roles in industry. Pharmaceutical and biotechnology companies increasingly require scientists with combined synthetic and bioanalytical skills. Therefore, there are many potential employability options for the student, in addition to postdoctoral opportunities in this highly active research field.

Find out more:
https://butler-researchgroup.wixsite.com/welcome
https://www.lboro.ac.uk/science/study/postgraduate-research/studentships/
Entry requirements:
Applicants should have, or expect to achieve, at least a 2:1 Honours degree in Chemistry. A relevant Master’s degree and/or experience in organic chemistry or chemical biology will be an advantage.

Funding information:
This studentship will be awarded on a competitive basis to applicants who have applied to this project and/or any of the advertised projects prioritised for funding by the School of Science.
The 3-year studentship provides a tax-free stipend of £15,009 (2019 rate) per annum for the duration of the studentship, plus tuition fees at the UK/EU rate. This studentship is only available to those who are eligible to pay UK/EU fees.
Contact details:
Dr Stephen Butler

+44 (0)1509 222577

How to apply:

All applications should be made online at http://www.lboro.ac.uk/study/apply/research/. Under programme name, select Chemistry.

Quote reference number: SJB/CM/2020

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