On-Column Monitoring of Protein Purification by Spectroscopic Techniques

Applications are invited for a 4 year iCASE PhD studentship position fully funded by the BBSRC and GSK and based in the Departments of Life Sciences and Chemical Engineering at Imperial College London.

Monoclonal antibodies (mAbs) represent effective therapies for the treatment of a range of chronic and life threating diseases including rheumatoid arthritis and cancer. However, the cost of production of therapeutic antibodies is significantly higher than small molecule drugs, mainly due to the complex isolation process which involves a very expensive Protein A affinity capture step.

This project builds on our previous research showing the power of Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR) for probing the build-up of contaminants and the effects of cleaning protocols on resin life span using ex situ resin beads and a microfluidic set up (Boulet-Audet et al. 2015, Analytical Bioanalytical Chemistry 407, 7111–7122; Boulet-Audet et al, 2016, Scientific Reports 6, 30526). This project focuses on the further development of novel spectroscopic approaches to directly monitor the Protein A affinity capture step, on-column. For this we can use Raman spectroscopy, where a laser beam will probe through a small window in the column and the backscattering produced will be used in confocal mode giving information on what changes are taking place at a range of depths (up to ca. 200 µm with steps of 1-3 µm). In this project, we also aim to explore linking a single column with focal plane array detector for FTIR imaging, allowing multiplexing of many signals from different locations in a column simultaneously. The findings from these studies will provide novel insights into the causes and cures of resin decay and validate new systems with the potential to be of widespread use to industry. This project will provide excellent training for the student in areas as diverse as biopharmaceuticals, protein purification, chromatography, Raman spectroscopy and FTIR spectroscopic imaging and will include a secondment to GSK.

Applicants should have a BSc in Chemistry/Chemical Engineering or related discipline, at 2:1 level or better, and an associated Masters degree or an equivalent level of professional qualifications or experience. Knowledge and experience of relevant spectroscopic techniques is highly desirable but not essential.
UK or EU candidates, who have lived in the UK for 3 years, are eligible for this studentship.

Closing date for applications: 27th April 2018

Further details on this project are available from Professor Bernadette Byrne ([Email Address Removed]) and Professor Sergei G. Kazarian ([Email Address Removed]). Information about the research groups is available at www.imperial.ac.uk/people/b.byrne and www.imperial.ac.uk/people/s.kazarian.