The effect of probiotics on intestinal epithelial cell function

The ATP-binding Cassette (ABC) transporters expressed in the intestine act as a defence mechanism, effluxing xenobiotics out of intestinal epithelial cells. ABC transporters possess broad substrate specificity and transport an array of therapeutics, including antibiotics, cardiotonics, HIV protease inhibitors, statins, immunosuppressants and anti-cancer agents. As such, ABC transporter activity can significantly impact oral drug bioavailability and may consequently influence the efficacy of disease treatments.

Consumption of dietary probiotics has increased substantially in recent years. Little is known about the effect of probiotics on ABC transporters, although Sakaena et al (2011) report probiotics, or probiotic-associated factors, are able to increase transporter expression and function. Consequently, upregulation of functional activity may influence transport of drugs across the intestinal epithelium.

We have shown that a human ABC transporter transports the dietary procarcinogen benzo[a]pyrene, thereby highlighting its cytoprotective function in human intestine [1]. Modulation of transporter activity by probiotics, or probiotic-associated factors, may therefore have the potential to increase the protective ability of the intestinal epithelium.

The aim of this PhD study is to investigate the effects of dietary probiotics and probiotic-associated soluble factors on transporter functional activity in human intestinal epithelial cells.

Training will be provided in aseptic cell culture, cell viability assays, measurement of transporter activity, measurement of transporter expression (western blotting), maintenance of probiotic bacteria and inoculation of mammalian cell cultures.

This project will be conducted within Manchester Pharmacy School, one of the UK’s leading centres for pharmacy research. The successful candidate will form part of a collaborative research team with research interests in development of model cell systems (e.g. human intestine, blood-brain barrier) to study transporter proteins and interests in understanding the interactions between bacteria and host.

Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in microbiology, biochemistry, cell biology, pharmacology, pharmacy or related subject. A Masters qualification would be beneficial.

This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship. Annual fee rates for this project, due to commence from September 2015 onwards, are:

*UK/EU nationals: £14, 000
Non-EU nationals: £26, 500

Please direct applications in the following format to Dr Jeff Penny ([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.

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.

http://www.pharmacy.manchester.ac.uk/staff/19436
http://www.pharmacy.manchester.ac.uk/staff/McBain

http://www.pharmacy.manchester.ac.uk