The role of intracellular calcium in cigarette smoke-induced CFTR internalization

Reference Code: CB098

Closing Date: 10th October 2013

Details:

Name of the supervisors
Dr M Gray, Institute for Cell and Molecular Biosciences (ICaMB)

Dr R Tarran, University of North Carolina

Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)

Duration of the award Three year PhD

Project description
This is a collaborative project between the Newcastle Epithelial Research Group and the CF/Pulmonary Research & Treatment Centre, University of North Carolina at Chapel Hill, a leading lung Institute in the USA. This is an exciting opportunity for a dynamic student to study at two leading lung/epithelial biology Institutes dedicated to understanding the mechanisms underlying cigarette smoke-induced airway disease.

Background
Chronic obstructive pulmonary disease (COPD) affects 64 million people and is currently the fourth leading cause of death worldwide. The most common cause of COPD is cigarette smoking and multiple lines of evidence suggest that tobacco exposure negatively affects the lung’s innate defence system. This sets the stage for chronic inflammation and cellular remodelling (mucus cell metaplasia) as cells adapt to the chronic inflammatory environment. We have shown that acute cigarette smoke (CS) exposure leads to an inhibition of the chloride channel, CFTR, in human airway cells. This leads to a decrease in airway surface liquid and mucus dehydration, factors known to be associated with increased inflammation and potentially the development of chronic bronchitis. However, little is known about the fundamental mechanism(s) responsible for the inhibition of CFTR following CS exposure, although it is linked to a sustained increase in intracellular calcium ions which appear to come from lysosomes.

The aims of the project will be to (i) determine the spatio-temporal relationship between CS/chemical-induced calcium release and compare this to nucleotide-mediated and ionophore-mediated calcium release, in primary human airway cells and model human cell lines; (ii) identify the pathway for calcium release from lysosomes induced by CS/chemicals and (iii) use electrophysiological techniques to measure calcium currents in isolated lysosomes and determine the effect of CS/chemicals on calcium channel activity.

Value of the award and eligibility
Depending on how you meet the BBSRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,726 (2013/14). A partial award covers fees at the UK/EU rate only.

Person specification
Candidates should have or expect to achieve a first-class or upper-second-class Honours degree in a relevant science subject plus normally further research experience and/or a further qualification such as for example an MRes

How to apply
You must complete the University’s postgraduate application form selecting ‘PhD in the Faculty of Medical Sciences – Cell and Molecular Biosciences’ as the programme of study. Once you have selected the programme, please insert the studentship/partnership reference number CB098. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CB098.

Further information:

For further details, please contact:
Dr Mike Gray
E-mail: m.a.gray@ncl.ac.uk
Telephone: +44 (0) 191 222 7592