PhD Studentship The Mechanism of TRPA1 Activation

To celebrate the University’s research successes, the University of Hull is offering 20 full-time UK/EU PhD Scholarship or International Fees Bursaries for candidates applying for the research areas within the six interdisciplinary research areas, including  following project in the theme of Health and Wellbeing to candidates with or expecting a 1st, 2(i), or equivalent degree

Closing date: – 3rd February 2014.
Studentships will start on 29th September 2014.

Supervisors: – Dr L Sadofsky : (HYMS), Dr A Boa (Chemistry), Professor A Morice (HYMS).

The TRP channels are a superfamily of cation channels divided in mammals in to six families. This project will focus on TRPA1 (transient receptor potential ankyrin-1). This ion channel detects noxious stimuli both physical and chemical. For example, TRPA1 is activated by cold temperatures and acrolein (found in cigarette smoke) as well as many plant extracts including cinnamon (cinnamaldehyde), menthol and the hot component of wasabi (allyl isothiocyanate). It is clear that TRPA1 is activated by an ever increasing list of noxious compounds and therefore has an important role in the body to detect harmful stimuli. It is now known that these ion channels are important for inflammation, pain perception, itch and the cough reflex. The important role that TRPA1 has in the body makes it an exciting target for drug development. However, in order to develop drug-like antagonists it will be important to understand the mechanisms of activation and/or blocking of TRPA1.

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One mechanism of activation of TRPA1 is through covalent modification of specific cysteine residues on the N terminus of the protein by reactive groups on the agonists – e.g. unsaturated carbonyl groups on acrolein and cinnamaldehyde. TRPA1 is also activated by plant products including menthol, eugenol (from cloves) and thymol (from thyme), which are incapable of covalently modifying cysteine residues. In order to develop drug-like antagonists it will be important to understand the structural basis for non-covalent mechanisms of activation and blocking of TRPA1. These mechanisms are currently undetermined. We therefore hypothesise that functional groups present on natural plant products activate TRPA1 by a distinct non-covalent mechanism. This project will be a collaboration between the Department of Chemistry and the Hull York Medical School. The successful applicant will have a chemistry, life sciences or related first degree, and be keen to develop both the pharmacological and synthetic chemistry skills needed for this research project. The student will synthesise novel compounds which they will test in TRPA1 expressing cell lines. Evaluating channel activation and antagonism by these compounds will help determine the mechanism of non covalent activation of the channel by the related natural plant products.

To apply for this post please click on the ‘Apply’ button below.

Full-time UK/EU PhD Scholarship will include fees at the ‘home/EU’ student rate and maintenance (£13,726 in 2013/14) for three years, depending on satisfactory progress.

Full-time International Fee PhD Studentships will include full fees at the International student rate for three years, dependant on satisfactory progress.

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PhD students at the University of Hull follow modules for research and transferable skills development and gain a Masters level Certificate, or Diploma, in Research Training, in addition to their research degree.

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