Unravelling the solution structures and stability of industrially-important antibodies with and without glycans by a multidisciplinary scattering, ultracentrifugation and modelling approach

Supervisors:
Prof Steve Perkins, Dept. Structural and Molecular Biology, UCL;
Prof Paul Dalby, Department of Biochemical Engineering, UCL;
Dr James Doutch, Instrument Scientist, ISIS;
Dr Rob Rambo, Instrument Scientist, Diamond.
Website: http://www.ucl.ac.uk/smb/perkins/
Email: [Email Address Removed]

The glycosylation of glycoproteins is a major determinant of their stability, and glycans also affect their aggregatibility (precipitation). An understanding of this topic is essential for improving manufacturing processes and is at the forefront of this exciting field. Our extensive background in antibodies, glycosylation and scattering indicates that we are ideally positioned to investigate antibody glycosylation in detail. We will compare both glycosylated and deglycosylated antibodies, together with complementary studies of anionic oligosaccharides, using a combination of X-ray and neutron scattering, analytical ultracentrifugation and computational simulation methods using state-of-the art force-fields, molecular dynamics/Monte Carlo engines, and solvation models. The two overall aims of this project are to (i) identify how the solution properties of glycans affect antibody stability and manufacture and (ii) develop a pipeline of new methods for the rapid atomistic modelling of antibody conformations based on X-ray and neutron scattering fits in order to evaluate the manufacturability of variously glycosylated antibodies. The project represents an important extension of the CCP-SAS atomistic modelling project jointly funded between EPSRC and NSF (http://www.ccpsas.org/).

UCL is one of the top UK research universities. The four-year PhD project is jointly funded by UCL through the EPSRC Centre for Doctoral Training (CDT) in Emergent Macromolecular Therapies (https://www.ucl.ac.uk/biochemeng/industry/epsrc/cdt), and by the Diamond Light Source and the ISIS Pulsed Neutron Source. This multidisciplinary project would suit a candidate with a Biochemistry, Biochemical Engineering, Physics, or Computational Science degree who is keen to learn about proteins in solution and their molecular modelling. The student is expected to spend 3 years at UCL, where the CDT offers additional PhD training and access to industry, and 1 year at Diamond and ISIS. Applicants will need to satisfy UK residence eligibility. The PhD studentship position is open until this has been filled; the start date is 1st October 2016.

Please send an email to Prof Perkins citing EPSRC-Diamond-ISIS PhD studentship in the subject line. Outline your interest and experience. Please include your CV with all academic grades and the details of two academic referees that we can contact.