About the Project
This BBSRC CASE award is aimed at developing a better understanding of the role excipients play in drug delivery and bioavailability. The award is sponsored by Croda Pharmaceuticals, who are focussed on developing active pharmaceutical ingredients in conjunction with the formulations and excipients required to improve delivery and performance of the drugs. This project will develop our understanding of how excipients interact with biologically active pharmaceutical ingredients (from simple peptides to proteins and monoclonal antibodies) in formulations developed by the biopharmaceutical industry.
The project will focus on the use of biomolecular Mass Spectrometry (MS), together with a range of other biophysical techniques. Mass spectrometry is well-recognized throughout industry and academia as an essential tool in biomolecule characterization, providing unique insights into protein and peptide structure and conformation, particularly when used in conjunction with advanced separation techniques (e.g. Ion Mobility Spectrometry) and chemical labelling methodologies (e.g. Hydrogen/Deuterium Exchange (HDX), Fast Photochemical Oxidation of Proteins (FPOP) and chemical cross-linking).
The novelty of this project lies in applying these structural MS techniques, and developing new methods and technologies where appropriate, to map changes in protein conformation and stability resulting from the presence of excipients used in drug delivery systems.
The Mass Spectrometry Facility (Manager Dr James Ault) in the Faculty of Biological Sciences is well-equipped with state-of-the-art instrumentation to perform the techniques outlined above and the successful candidate will be provided will full training on all the equipment. The Faculty also boasts a further nine Research Facilities providing equipment and expertise to aid biophysical, structural and cellular characterization of these complex systems.
This research will be of importance in academia and in the medical and biopharmaceutical fields, and will provide the student with expertise in a broad base of biophysical and analytical skills to equip this person for a rewarding scientific career.
For further information see our University of Leeds web-sites:
http://www.astbury.leeds.ac.uk and
http://www.personal.leeds.ac.uk/~fbsmaspe/
in addition to the Croda web-sites:
https://www.croda.com/en-gb/products-and-markets/pharmaceuticals and
https://www.crodahealthcare.com/en-gb
or contact: [Email Address Removed]; [Email Address Removed]; [Email Address Removed] directly.
Funding Notes
This is a 4 year BBSRC CASE studentship with Croda Pharmaceuticals, managed under the White Rose Mechanistic Biology DTP. The successful applicant will receive the usual BBSRC fees and stipend, plus an additional stipend from Croda. The PhD will start in October 2018.
Applicants should have, or be expecting to receive, a 1st or 2.1 Hons degree in Chemistry, Biochemistry, or a related subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
Please see our website for more information: http://www.fbs.leeds.ac.uk/postgraduate/
References
Recent related publications using mass spectrometry to study protein conformation and function from Ashcroft, Sobott, and Ault:
1. Monitoring co-populated conformational states during protein folding events using electrospray ionisation - ion mobility spectrometry – mass spectrometry,
D. P. Smith, K. Giles, R. H. Bateman, S. E. Radford, A. E. Ashcroft,
J. Am. Soc. Mass Spectrom., 18, 2180-2190, 2007.
2. Screening and characterising small molecule inhibitors of amyloid formation using ion mobility spectrometry-mass spectrometry,
L. M. Young, J. C. Saunders, R. A. Mahood, C. H. Revill, R. J. Foster, L. H. Tu, D. P. Raleigh, S. E. Radford, A. E. Ashcroft,
Nat. Chem., 7, 73-81, 2015.
3. Using hydroxyl radical footprinting to explore the free energy landscape of protein folding, A. N. Calabrese, J. R. Ault, S. E. Radford, A. E. Ashcroft,
Methods, 89, 38-44, 2015.
4. Native Mass Spectrometry for the Characterization of Structure and Interactions of Membrane Proteins,
J. F. van Dyck, A. Konijnenberg, F. Sobott,
Methods Mol Biol., 1635, 205-232, 2017.
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