How do proteins unfold under hydrodynamic flow? (BBSRC CTP with Medimmune)

Supervisor(s)

Dr David Brockwell

Prof. Sheena Radford

Project description

Protein aggregation is highly problematic to the £200bn biopharmaceutical industry as it can pose dangers to the patient (loss of efficacy of the protein drug and induction of the immune response) and can increase time-to-market and, therefore, cost of goods. Over the last four years, we have shown that fluid-driven forces can drive the aggregation of a small test protein (BSA) by triggering the unfolding, exposing new protein surfaces with greater self-affinity, leading to aggregation (see Dobson et al. (2017) Proc Natl Acad Sci USA. 114:4673-4678).

The mechanism of fluid-flow induced unfolding remains 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, biophysical characterisation and hydrodynamic flow to identify the mechanism of flow-induced unfolding of test proteins and biopharmaceuticals provided by Medimmune.

This fundamental study will ultimately facilitate the economic production of current and next generation high-value bio-pharmaceuticals.

Key benefits

BBSRC funded Medimmune Collaborative Training Partnership 4 year studentship. Studentships covers UK/EU fees and stipend (c.£14,553) for 4 years to start in Jan 2019.

Entry requirements

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. If English if not your first language you will be required to meet the university language requirements before registration https://www.leeds.ac.uk/info/123100/admissions/143/entry_requirements

How to apply

Please apply online https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon

Please include supervisor name and project title.  A research proposal is not required.  Please upload a CV and transcripts.

How to apply (email)

fbsgrad@leeds.ac.uk

How to apply (phone)

+44 (0)113 343 8186