Structural and dynamical characterisation of therapeutic protein formulations by mass spectrometry and simulation
Antibody-based therapeutics and diagnostics are major breakthrough applications of proteins. Getting them to patients is often challenging due to their poor stability and tendency to aggregate. Formulation of such antibodies is currently an empirical and time-consuming process that typically involves wide-searches of excipients and solution conditions using automated screening platforms. This project will focus on combining biophysical techniques, particularly mass spectrometry, with molecular dynamics simulations, to elucidate conformational dynamics changes within protein formulations. This work will inform research into the mechanism of action of formulation additives, and increase our understanding of the protein features that lead to stabilisation. The knowledge gained within this project will be of direct benefit to the biopharmaceutical development, manufacturing and formulation industry.
UCL is one of the top UK research universities. The four-year PhD project is funded by the EPSRC and will be linked to the Future Targeted Healthcare Manufacturing Hub at UCL (https://www.ucl.ac.uk/biochemical-engineering/research/research-and-training-centres/future-targeted-healthcare-manufacturing-hub), and is sponsored by LGC (https://www.lgcgroup.com).
LGC acts as the UK National Measurement laboratory (NML) for chemical and biological measurements, a unique role funded by UK Government (BEIS_Department of Business, Energy and Industrial Strategy) to provide confidence in measurement and support innovation. The NML works closely with government, academia and industry to understand, address and manage the measurement challenges they face, delivering world-leading chemical and bio-measurement science to keep these measurements running smoothly. The successful candidate will work in the organic mass spectrometry laboratory, equipped with a broad range of mass spectrometers including QQQ, QToF, IMS-MS, Orbitrap, MALDI-ToF coupled with diverse separation science instrumentation such as nano, capillary and ultra-high-pressure liquid chromatography and gas chromatography.
The four-year PhD project is funded by the EPSRC with the standard EPSRC Studentship stipend plus London weighting. This multidisciplinary project would suit a candidate with a Biochemistry, Molecular Biology, Biochemical Engineering, or Chemistry degree, with interests in biophysics, structural biology, modelling, analytical chemistry and data mining. The Department of Biochemical Engineering offers PhD skills and sector training. Applicants will need to satisfy UK residence eligibility. The application deadline is 15th May 2020.
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FTE Category A staff submitted: 54.16
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