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Assessment of protein-protein interactions and microrheology using Fluorescence Correlation Spectroscopy

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  • Full or part time
    Dr Pluen
    Dr Curtis
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The study of nonspecific protein-protein interactions (PPI) is of interest not only for biochemical processes or disease but for interactions influencing protein aggregation, solution viscosity, and phase transitions. Intermolecular interactions coupled with conformational factors have been implicated in diseases such as cataract formation, sickle-cell anaemia and in amyloid diseases e.g. Alzheimer’s disease.

However PPI are also fundamental from a biopharmaceutical perspective, as they become important during the development of concentrated monoclonal antibody solutions (1). Modifying attractive and repulsive forces between proteins leads to conformation changes and ultimately affects the resistance to flow thus rheology is often complementary to light scattering in PPI studies (2). Recently, Holyst et al. (3) have demonstrated that Fluorescence Correlation Spectroscopy could be utilised to determine the microrhelogical properties of polyethylene glycol solutions.

The present project thus seeks to:
(i) evaluate the microrheological behaviour of model proteins at high concentrations upon modification of the attractive repulsive forces balance and
(ii) to compare this information to traditional rheological measurements and
(iii) and evaluate the pertinence of current models.

Training in all relevant techniques will be provided including fluorescence correlation spectroscopy, image analysis, static and dynamic light scattering, and rheology.

The project will be conducted within Manchester Pharmacy School, recently confirmed as the leading UK research base for Pharmacy following the 2014 Research Excellence Framework. The nature of the project involves working in a multidisciplinary environment. The candidate is expected to have a strong will to learn different scientific aspects.

Candidates are expected to hold a minimum upper-second honours undergraduate degree (or equivalent) in a biochemical engineering, biophysics or relevant physical sciences subject. A Masters qualification in a similar area would be a significant advantage.

This 4-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/ sponsorship and is due to commence from January 2017 onwards.

Any enquiries relating to the project and/or suitability should be directed to Dr Pluen ([email protected]). Applications are invited on an on-going basis but early expression of interest is encouraged.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

1. Z Hamrang, NJW Rattray and A Pluen, Trends in Biotechnology, 2013, 31, 448
2. D Roberts, R Keeling, M Tracka, CF Van der Walle, S Uddin, J Warwicker and R Curtis,Molecular Pharmaceutics, 2015, 12, 179.
3. A Ochab-Marcinek, SoftMatter, 2011, 7, 7366

How good is research at University of Manchester in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 112.65

Research output data provided by the Research Excellence Framework (REF)

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