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Dr Alain Pluen, Prof David Clarke
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Protein-based therapeutics such as antibodies emerged recently as new generation of drugs aimed to treat a wide range of diseases. Manufacturing of these therapeutic proteins often suffers from aggregation and particle formation during different stages of the bioprocess, especially when proteins are formulated at very high concentrations for administration into patients.
Often aggregation becomes apparent only at very high protein concentrations, such as those used in the final formulations, leading to high viscosity and appearance of particles. This may be exacerbated by prolonged storage of protein solutions, after they are manufactured and before they are used on patients. Therefore, testing highly-concentrated protein solutions for the presence or appearance of aggregates and particles is crucially important.
Recently concerns were raised regarding increased immunological risk of larger protein aggregates, sub-visible particles (Carpenter et al., J Pharm Sci 2009). Although questioned by the industry it is clear that reliable methods for their detection and quantification were missing (Singh et al., J Pharm Sci 2010). Thus, a new measurement method able to report on sub-visible particles formation in un-diluted protein solutions would be ideal.
Raster Image Correlation Spectroscopy (RICS), devised in 2005 (Digman et al., Biophys J 2005) to observe transport of proteins in cells, allows determining in situ simultaneously size and concentrations of fluorescently labelled specks undergoing Brownian motion. We have recently demonstrated (Hamrang et al., J. Pharm. Sci. 2012) that RICS can be used to observe the populations of proteins in solution as well as their changes following external stimuli.
The aim of this PhD project is to demonstrate that RICS is suitable to characterise the presence and formation of proteinaceous sub-visible particles in protein formulations.
The successful candidate will be based in a multidisciplinary environment and provided with training in all relevant aspects e.g. imaging, correlation spectroscopies, image analysis and regular protein analytical techniques. Upon completion, the candidate would be ideally placed to progress in several career directions, including bioprocessing or formulation research within the biopharmaceutical industry.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in a relevant biological/medical science, biophysics, chemistry, chemical engineering or pharmaceutical sciences subject.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to evidence their ability to provide self-arranged funding. Annual tuition fees for this project are currently:
*UK/EU nationals: £11, 700
*Non-EU nationals: £22, 500
Please direct applications in the following format to Dr Alain Pluen ([Email Address Removed]):
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date
• Evidence of funding
Enquiries relating to the project and/or suitability should be directed to Dr Pluen at the address above.
*Applicants should note that these fee rates apply to the 2011/12 academic year and are subject to increase ahead of September 2012.
http://www.pharmacy.manchester.ac.uk/
http://www.pharmacy.manchester.ac.uk/staff/19437
Often aggregation becomes apparent only at very high protein concentrations, such as those used in the final formulations, leading to high viscosity and appearance of particles. This may be exacerbated by prolonged storage of protein solutions, after they are manufactured and before they are used on patients. Therefore, testing highly-concentrated protein solutions for the presence or appearance of aggregates and particles is crucially important.
Recently concerns were raised regarding increased immunological risk of larger protein aggregates, sub-visible particles (Carpenter et al., J Pharm Sci 2009). Although questioned by the industry it is clear that reliable methods for their detection and quantification were missing (Singh et al., J Pharm Sci 2010). Thus, a new measurement method able to report on sub-visible particles formation in un-diluted protein solutions would be ideal.
Raster Image Correlation Spectroscopy (RICS), devised in 2005 (Digman et al., Biophys J 2005) to observe transport of proteins in cells, allows determining in situ simultaneously size and concentrations of fluorescently labelled specks undergoing Brownian motion. We have recently demonstrated (Hamrang et al., J. Pharm. Sci. 2012) that RICS can be used to observe the populations of proteins in solution as well as their changes following external stimuli.
The aim of this PhD project is to demonstrate that RICS is suitable to characterise the presence and formation of proteinaceous sub-visible particles in protein formulations.
The successful candidate will be based in a multidisciplinary environment and provided with training in all relevant aspects e.g. imaging, correlation spectroscopies, image analysis and regular protein analytical techniques. Upon completion, the candidate would be ideally placed to progress in several career directions, including bioprocessing or formulation research within the biopharmaceutical industry.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in a relevant biological/medical science, biophysics, chemistry, chemical engineering or pharmaceutical sciences subject.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to evidence their ability to provide self-arranged funding. Annual tuition fees for this project are currently:
*UK/EU nationals: £11, 700
*Non-EU nationals: £22, 500
Please direct applications in the following format to Dr Alain Pluen ([Email Address Removed]):
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date
• Evidence of funding
Enquiries relating to the project and/or suitability should be directed to Dr Pluen at the address above.
*Applicants should note that these fee rates apply to the 2011/12 academic year and are subject to increase ahead of September 2012.
http://www.pharmacy.manchester.ac.uk/
http://www.pharmacy.manchester.ac.uk/staff/19437
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