School of Medicine, Dentistry
and Biomedical
Sciences
DEL Postgraduate Research Opportunity for
September 2011 (SUBJECT TO FUNDING)
Infection and Immunity
Exploitation of well-differentiated primary paediatric airway
epithelial cell cultures (WD-PAECs) to study RSV/human host
interactions
Supervisors:
(email u.power@qub.ac.uk)
(email m.shields@qub.ac.uk)
Candidates should have or expect to obtain a 2:1 or higher Honours degree or
equivalent in Microbiology, Biochemistry or other relevant Biology degree.
Further information is available on the School website at
http://www.qub.ac.uk/schools/mdbs/ (Click on Postgraduate Studentships).
Potential candidates are encouraged to contact the supervisor prior to submitting an
application.
Abstract
Respiratory syncytial virus (RSV) is the principle cause of severe respiratory viral disease
in young infants. The WHO estimates that it causes 63 million infections and 160,000
deaths annually. In the UK, approximately 20,000 infants are hospitalised during annual
RSV epidemics.
Despite its medical importance, there are no vaccines or specific
therapeutics. The mechanisms by which RSV causes disease are poorly understood.
However, respiratory epithelium is clearly the principle target for RSV infection.
Consequently, RSV interaction with the epithelium is likely to be responsible, at least in
part, for the associated pathogenesis.
To study this interaction we developed
physiologically authentic ex vivo/in vitro models of RSV infection based on welldifferentiated primary paediatric airway epithelial cells (WD-PAECs).
These multilayered 3 dimensional primary cell cultures look and behave like they would in the nasal
tract and lungs, with very active cilia, lots of mucus produced by goblet cells and intact
tight junctions. Over the last few years we have developed extensive expertise in the
culture of WD-PAECs and have made significant advances in characterising them as
models of RSV infection. Indeed, our data suggest that RSV infection causes
cytopathological changes to WD-PAECs that are remarkably similar to those observed in
the infant lung epithelium of fatal RSV infections. These data have been the subject of
award-winning presentations and will be central to a number of publications over the next
few months.
The current studentship project will build on these observations to further characterise
the interaction of RSV with the respiratory epithelium. In particular, the project will focus
on innate immune and cytopathological responses to RSV infection of WD-PAECs.
Innate immune response studies will determine the roles of type I and the more recently
identified type III interferons in inducing antiviral responses to RSV in WD-PAECs. The
cytopathology studies will determine the consequences of RSV infection on upregulation
of specific cell surface proteins that may be implicated in the pathogenesis of RSV in
humans. As such, these studies might provide the basis for identifying markers of RSV
pathogenesis in humans and consequently help orientate therapeutic options for RSVinduced disease.
This project provides a rare and exciting opportunity to study host/virus interactions in a
highly relevant model. It will lead to a better understanding of how RSV causes disease
and may provide insights for therapeutic options against this medically important virus.
CLOSING DATE: Friday 11 February 2011
Eligibility for both fees and maintenance (£13,590 in 2010/11 depends on the applicants being either an ordinary
UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding
the start of the studentship. Non UK residents who hold EU residency may also apply but if successful may
receive fees only.