Environmental pollutants as modulators of enteroendocrine signalling; do man-made chemicals interfere with human physiology?

The Rowett Institute has an international reputation for teaching and research in human nutrition and food science. As part of its funding through the Scottish government we are advertising a number of high-profile PhD studentships in nutrition, food science, microbiology and analytical chemistry.

The food chain is subject to potential contamination with toxic materials. While acute toxicity is rare in the Western world, chronic exposure to toxic compounds can potentially lead to detrimental health outcomes. Endocrine disruptors can mimic or antagonize the effect of hormones thereby influencing cancer susceptibility. Other chemicals can interfere with enteroendocrine signalling by bile acids and thereby affect metabolic health outcomes. Many man-made chemicals present in pesticides, food wrapping and even cosmetics, have become enriched in the environment over recent decades.

At present toxins are typically detected using chemical or immunological methods. These methods are highly specific but typically only detect a single chemical compound while potentially missing related toxic compounds, derived from chemical or microbial degradation. In contrast cell-based assay systems allow the rapid detection of a wide range of related toxins with similar toxicities.

Cells sense toxic substances via the aryl hydrocarbon receptor and members of the nuclear receptor superfamily, which includes sex hormone receptors and receptors for bile acids, fatty acids, xenobiotics and vitamins. These proteins combine a ligand binding domain and a DNA binding domain. Upon binding of a suitable ligand, the nuclear receptor associates with coactivators and promotes transcription of target genes encoding detoxifying proteins.

The proposed project aims to:

1. develop cell-based assay systems based on nuclear receptors which mediate physiological regulation in the context of diet,

2. use the cell-based assay systems to analyse the potential effects of environmental pollutants on entero-endocrine processes,

3. utilise the cellular components of the toxin response to develop in vitro systems which can detect toxins in simple assay formats.

Reporter cell lines will be established using CRISPR and viral vector technologies, optimised for maximum sensitivity and dynamic range, and validated using known environmental pollutants. The assay systems will be used to investigate the impact of environmental toxins on physiological signalling processes. Protein domains relevant for nuclear receptor signalling will be expressed in mammalian and bacterial host systems, purified and analysed using biochemical and biophysical methods. The purified protein domains will then be used to establish biosensors which can be used for rapid toxin testing outside the lab environment.

The proposed project is multidisciplinary and builds on the supervisory team’s expertise in the areas of cell-based assay systems, bile acid signalling, nuclear receptor analysis and biosensor development. The student will receive training in molecular endocrinology and nutrition, receptor biology and pharmacology, experimental design, data collection and analysis.

Essential background of student:

Degree in a molecular biology, cell biology, pharmacology, biochemistry or a similar discipline. Familiarity with cell culture and molecular cloning techniques would be an asset.

Informal enquiries would be welcomed for a discussion, Please contact the lead supervisor, Dr Andreas Kolb ([Email Address Removed]) for more information.

--------------------------------------------------

This project will be based within the Rowett Institute, part of the School of Medicine, Medical Sciences and Nutrition, at the University of Aberdeen. The Rowett Institute is located on the Foresterhill Health Campus, one of the largest clinical complexes in Europe, which also includes the Institute of Applied Health Sciences, a large teaching hospital and the the Institute of Medical Sciences (IMS). 

--------------------------------------------------

APPLICATION PROCEDURE:

International applicants are eligible to apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £17,000 per annum)

• Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
• You should apply for the Degree of Doctor of Philosophy in Medical Sciences to ensure your application is passed to the correct team
• Please clearly note the name of the supervisor and exact project title on the application form. If you do not mention the project title and the supervisor on your application it will not be considered for the studentship.
• Candidates should have (or expect to achieve) a minimum of a 2:1 Honours degree at undergraduate level.
• General application enquiries can be made to [Email Address Removed]