Analysing the factors that regulate expression of blood-brain barrier drug transporter proteins
In order to treat diseases associated with the central nervous system (CNS), e.g. cancer, Parkinson’s disease, depression, it is essential for therapeutic drugs to be able to penetrate into the brain. However, efficient drug delivery to the CNS is extremely challenging since drugs must cross the blood-brain barrier (BBB), whose function is to protect the brain from exposure to xenobiotics, including therapeutic drugs.
Efflux transporters are also involved in the transport of endogenous physiological compounds, including beta-amyloid associated with Alzheimer’s disease, hormones and numerous metabolites, thereby preventing accumulation of the latter in the CNS and helping maintain CNS homeostasis.
Whilst efflux transporters (including P-glycoprotein and breast cancer resistance protein) expressed in BBB endothelial cells can interfere with drug delivery and have important roles to play in both physiological and pathophysiological events, little is known about what regulates transporter expression and activity in the BBB.
Therefore, the aim of this project is to investigate how the expression of efflux transporters located in BBB endothelial cells is regulated in physiological and pathophysiological conditions.
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. Research will be conducted in collaboration with Dr. Pablo Torres-Vergara from the Faculty of Pharmacy, Universidad de Concepcion, Chile. The successful candidate will form part of a collaborative, multi-disciplinary research team with research interests in understanding the mechanisms controlling the regulation of transporter protein expression and activity.
Studies will employ in vitro models of the BBB and training will be provided in aseptic cell culture, cell viability assays, measurement of transporter activity and molecular biological techniques.
Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in biochemistry, cell biology, pharmacology, pharmacy or related subject. A Masters qualification is highly desirable.
This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship. Fee rates for this project, due to commence from September 2016 onwards, are:
*UK/EU nationals: £14, 000
Non-EU nationals: £27, 500
Please direct applications in the following format to Dr. Jeffrey Penny (firstname.lastname@example.org):
• 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.
Any enquiries relating to the project and/or suitability should be directed to Dr. Penny. Applications are invited on an on-going basis but early expression of interest is encouraged.
*UK/EU tuition fees are subject to an annual inflationary increase, anticipated to be approximately 2.5% p.a.
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