Reference number: CM/SJB-Un1/2020
Start date of studentship: 1st October 2020
Closing date of advert: 22th August 2020
Primary supervisor: Dr Stephen Butler
Secondary Supervisor: Dr Benjamin Buckley
The aim of this PhD project is to develop molecular probes that react rapidly with specific reactive oxygen and nitrogen species (RONS, e.g. peroxynitrite), producing a luminescent signal that enables precise measurement of the concentration of the target species. This will provide a better understanding of the roles in RONS in cell biology and the mechanisms of transport of RONS into cells. Crucially, this could facilitate the development of more effective therapies and devices, tailored to delivering specific levels of RONS to targeted sites within cells and enabling safe doses of treatment to be determined.
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Full Project Detail
Peroxynitrite (ONOO−) is a powerful and short-lived oxidant formed in vivo, which can react with most biomolecules directly. Elevated intracellular levels of ONOO− can lead to significant damage to lipids, proteins and DNA and has been implicated in several diseases including Alzheimer’s and Parkinson’s disease. To fully understand the roles of ONOO− in cell biology and disease, improved methods for the selective detection and real-time analysis of ONOO− are needed. Existing molecular probes suffer from short-lived fluorescence read-outs, which can be difficult to distinguish from the background fluorescence of biomolecules, and insufficient selectivity between reactive species (e.g. NO, hydroxyl radicals), precluding accurate measurements of ONOO–.
This project will develop a water-soluble, luminescent probe capable of rapid and sensitive detection of peroxynitrite in human serum, living cells and biological matrices. We will utilise the long luminescence lifetime of the probe to record time-resolved measurements of ONOO–, in different cell types, using a standard microplate reader. This will provide a better understanding of the roles of RONS in cell biology and the mechanisms of transport of RONS into cells. Crucially, this could facilitate the development of more effective therapies and devices, tailored to delivering specific levels of RONS to targeted sites within cells. The student will have the possibility to spend time working in the laboratories of collaborators (UK and Germany), to test the probes in biological and cellular assays.
The student will gain excellent training in a range of techniques including organic synthesis, photophysical analysis of luminescent probes, 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
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.
Dr Stephen Butler [email protected]
How to apply
All applications should be made online at https://www.lboro.ac.uk/study/postgraduate/apply/research-applications/
Under school/department name, select 'Chemistry'.
Please quote reference CM/SJB-Un1/2020. The deadline for applications is 22 August 2020.