Primary Supervisor: Dr Marie-Christine Jones, School of Pharmacy
Secondary supervisor: Dr Fabian Spill, Dr Deena Gendoo
PhD project title: Investigating the immunomodulatory effect of combinatory phytochemical treatments
University of Registration: University of Birmingham
Background: In recent years, interest in plant extracts as therapeutic agents has grown steadily and so-called nutraceuticals or phytochemicals have been suggested as effective modulators of the immune response. While our understanding of their mechanism of action has improved significantly, the potential for phytochemical-phytochemical interactions has not been fully investigated. Although such combinations (either through combinatory therapy or through diet) are expected to be beneficial, competition for intracellular targets may reveal unexpected and/or undesirable effects.
Current in vitro methods to assess immunomodulatory drug combinations mostly rely on dose-response and toxicity data, with limited consideration for mechanism of action and factors that may affect intracellular drug accumulation. In this project, we hypothesise that a more holistic approach is required to fully understand the factors affecting synergy or antagonism. This should allow for the development of better tools and improve in vitro-in vivo correlations.
In addition to evaluating combinatory therapies, this project will also investigate the impact of encapsulating phytochemicals in nanoformulations. The latter strategy is often suggested to overcome issues of poor solubility and stability associated with most phytochemicals. However, depending on their properties, nanomedicines can also affect the immune response and, therefore, could affect phytochemical activity.
Objectives and methodology: The aims of the project will be achieved through:
- Testing the immunomodulatory activity of selected phytochemical (single agents and combinations) and their nanoformulation in vitro
- Investigating the expression of 1. selected markers of the inflammatory and immune response and 2. selected membrane transporters to elucidate their mechanism of action. The impact of different treatment schedules will also be studied (i.e. concomitant or staggered administration)
- Developing and validating analytical methods for the quantification of intracellular drug levels (e.g. HPLC)
- Comparing current tools available for the study of drug combinations and synergy
- Developing and refining mathematical and modelling tools to provide a more holistic in vitro assessment of drug combinations and synergy
BBSRC Strategic Research Priority: Understanding the Rules of Life: Immunology & Integrated Understanding of Health: Diet and Health & Pharmaceuticals
Techniques that will be undertaken during the project:
The following techniques will be used in this project: nanoparticle manufacture and characterisation (e.g. dynamic light scattering), cell culture, cell viability assay, flow cytometry, microscopy (fluorescent and/or electron), HPLC, ELISA, protein assay, modelling, drug synergy calculations.
Contact: Dr Marie-Christine Jones, University of Birmingham