About the Project
The flow induced aggregation pathway(s) of biopharmaceuticals such as IgGs, however, remain unexplored and consequently industry cannot reliably identify sequences that are inherently manufacturable. As antibody drug conjugates, next generation bi-specific platforms and gene therapy vectors are already posing an even greater manufacturing challenge, aggregation remains the major threat to the realisation of the enormous potentials of proteins in the bio-technology industry.
The goal of this BBSRC Collaborative Training Partnership PhD studentship between the Astbury Centre for Structural and Molecular Biology and Medimmune, therefore, is to apply Leeds’ unique expertise in protein (un)folding mechanisms, analytical mass spectrometry and hydrodynamic flow to identify the aggregation interfaces of antibodies provided by Medimmune.
To achieve this goal it is necessary to locate the aggregation interface and evaluate current or develop tools to allow their identification. This will be achieved by:
(i) measuring the flow-induced aggregation of a test set of scFvs that vary in their aggregation behaviour under different flow conditions.
(ii) assessing the ability of current bio-informatic approaches (such as SAP, CAMSOL and SOLUBIS) to predict the rank order of aggregation.
(iii) determining the mechanism of flow-induced unfolding. This will be achieved using a powerful combination of mass spectrometric and other labelling data to benchmark and / or constrain steered Molecular Dynamics simulations.
This fundamental study will ultimately facilitate the economic production of current and next generation high-value bio-pharmaceuticals.
Studentships covers UK/EU fees and stipend (c.£14,553) for 4 years to start in Oct 2018. Applicants should have/be expecting at least a 2.1 Hons. degree in a relevant subject. EU candidates require 3 years of UK residency in order to receive full studentship.
Please apply online here https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon and include a CV and transcripts with your application.
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